International Journal of Molecular Sciences

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13 pages, 3080 KiB

Open AccessArticle

Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines

by Angel Giovanni Arietta-García, Fernando Calzada, Israel Ramírez-Sánchez, Elihú Bautista, Normand García-Hernandez and Rosa María Ordoñez-Razo

Int. J. Mol. Sci. 2023, 24(15), 12406; https://doi.org/10.3390/ijms241512406 - 3 Aug 2023

Cited by 2 | Viewed by 1371

Abstract

Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. [...] Read more.

Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through in vitro assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its in silico comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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14 pages, 3270 KiB

Open AccessArticle

Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells

by Jaemoo Chun

Int. J. Mol. Sci. 2023, 24(15), 12397; https://doi.org/10.3390/ijms241512397 - 3 Aug 2023

Cited by 6 | Viewed by 1916

Abstract

Cisplatin is a potent chemotherapeutic drug for ovarian cancer (OC) treatment. However, its efficacy is significantly limited due to the development of cisplatin resistance. Although the acquisition of cisplatin resistance is a complex process involving various molecular alterations within cancer cells, the increased [...] Read more.

Cisplatin is a potent chemotherapeutic drug for ovarian cancer (OC) treatment. However, its efficacy is significantly limited due to the development of cisplatin resistance. Although the acquisition of cisplatin resistance is a complex process involving various molecular alterations within cancer cells, the increased reliance of cisplatin-resistant cells on glycolysis has gained increasing attention. Isoalantolactone, a sesquiterpene lactone isolated from Inula helenium L., possesses various pharmacological properties, including anticancer activity. In this study, isoalantolactone was investigated as a potential glycolysis inhibitor to overcome cisplatin resistance in OC. Isoalantolactone effectively targeted key glycolytic enzymes (e.g., lactate dehydrogenase A, phosphofructokinase liver type, and hexokinase 2), reducing glucose consumption and lactate production in cisplatin-resistant OC cells (specifically A2780 and SNU-8). Importantly, it also sensitized these cells to cisplatin-induced apoptosis. Isoalantolactone–cisplatin treatment regulated mitogen-activated protein kinase and AKT pathways more effectively in cisplatin-resistant cells than individual treatments. In vivo studies using cisplatin-sensitive and resistant OC xenograft models revealed that isoalantolactone, either alone or in combination with cisplatin, significantly suppressed tumor growth in cisplatin-resistant tumors. These findings highlight the potential of isoalantolactone as a novel glycolysis inhibitor for treating cisplatin-resistant OC. By targeting the dysregulated glycolytic pathway, isoalantolactone offers a promising approach to overcoming drug resistance and enhancing the efficacy of cisplatin-based therapies. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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17 pages, 5006 KiB

Open AccessArticle

Natural Cyclophilin A Inhibitors Suppress the Growth of Cancer Stem Cells in Non-Small Cell Lung Cancer by Disrupting Crosstalk between CypA/CD147 and EGFR

by Jang Mi Han, Sung Min Kim, Hong Lae Kim, Hee Jeong Cho and Hye Jin Jung

Int. J. Mol. Sci. 2023, 24(11), 9437; https://doi.org/10.3390/ijms24119437 - 29 May 2023

Cited by 4 | Viewed by 1969

Abstract

Non-small cell lung cancer (NSCLC) is a fatal malignant tumor with a high mortality rate. Cancer stem cells (CSCs) play pivotal roles in tumor initiation and progression, treatment resistance, and NSCLC recurrence. Therefore, the development of novel therapeutic targets and anticancer drugs that [...] Read more.

Non-small cell lung cancer (NSCLC) is a fatal malignant tumor with a high mortality rate. Cancer stem cells (CSCs) play pivotal roles in tumor initiation and progression, treatment resistance, and NSCLC recurrence. Therefore, the development of novel therapeutic targets and anticancer drugs that effectively block CSC growth may improve treatment outcomes in patients with NSCLC. In this study, we evaluated, for the first time, the effects of natural cyclophilin A (CypA) inhibitors, including 23-demethyl 8,13-deoxynargenicin (C9) and cyclosporin A (CsA), on the growth of NSCLC CSCs. C9 and CsA more sensitively inhibited the proliferation of epidermal growth factor receptor (EGFR)-mutant NSCLC CSCs than EGFR wild-type NSCLC CSCs. Both compounds suppressed the self-renewal ability of NSCLC CSCs and NSCLC-CSC-derived tumor growth in vivo. Furthermore, C9 and CsA inhibited NSCLC CSC growth by activating the intrinsic apoptotic pathway. Notably, C9 and CsA reduced the expression levels of major CSC markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2, through dual downregulation of the CypA/CD147 axis and EGFR activity in NSCLC CSCs. Our results also show that the EGFR tyrosine kinase inhibitor afatinib inactivated EGFR and decreased the expression levels of CypA and CD147 in NSCLC CSCs, suggesting close crosstalk between the CypA/CD147 and EGFR pathways in regulating NSCLC CSC growth. In addition, combined treatment with afatinib and C9 or CsA more potently inhibited the growth of EGFR-mutant NSCLC CSCs than single-compound treatments. These findings suggest that the natural CypA inhibitors C9 and CsA are potential anticancer agents that suppress the growth of EGFR-mutant NSCLC CSCs, either as monotherapy or in combination with afatinib, by interfering with the crosstalk between CypA/CD147 and EGFR. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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14 pages, 3209 KiB

Open AccessArticle

Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29

by Arti Nile, Jisoo Shin, Juhyun Shin, Gyun Seok Park, Suhyun Lee, Ji-Ho Lee, Kyung-Woo Lee, Beob Gyun Kim, Sung Gu Han, Ramesh Kumar Saini and Jae-Wook Oh

Int. J. Mol. Sci. 2023, 24(9), 8191; https://doi.org/10.3390/ijms24098191 - 3 May 2023

Cited by 6 | Viewed by 3061

Abstract

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. [...] Read more.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10–60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G₁-phase cells was observed with arrest at the G₂ phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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21 pages, 14593 KiB

Open AccessArticle

Plumbagin Exhibits Genotoxicity and Induces G2/M Cell Cycle Arrest via ROS-Mediated Oxidative Stress and Activation of ATM-p53 Signaling Pathway in Hepatocellular Cells

by Huan Liu, Wenchao Zhang, Lijie Jin, Shasha Liu, Liying Liang and Yanfei Wei

Int. J. Mol. Sci. 2023, 24(7), 6279; https://doi.org/10.3390/ijms24076279 - 27 Mar 2023

Cited by 17 | Viewed by 2852

Abstract

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, PLB), a naturally occurring naphthoquinone mainly isolated from the plant Plumbago zeylanica L., has been proven to possess anticancer activities towards multiple types of cancer. Although there has been an increasing amount of research regarding its anticancer effects, the association between oxidative [...] Read more.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, PLB), a naturally occurring naphthoquinone mainly isolated from the plant Plumbago zeylanica L., has been proven to possess anticancer activities towards multiple types of cancer. Although there has been an increasing amount of research regarding its anticancer effects, the association between oxidative stress, genotoxicity and the cell cycle arrest induced by PLB still remains unclear. Therefore, it is important to investigate their potential connections and the involvement of DNA damage and the ataxia telangiectasia mutated protein (ATM)-p53 signaling pathway in PLB’s anticancer mechanism. The present study showed that PLB exposure significantly reduced HCC cell viability and colony formation. In addition, PLB-induced G2/M cell cycle arrest, oxidative stress, and DNA damage was detected, which could be almost blocked by NAC pretreatment. PLB could trigger a DNA damage response by activating cell cycle checkpoints such as ATM, checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2) and p53. Meanwhile, the key modulator of the G2/M transition factor, Cell Division Cycle 25C (cdc25C), was significantly downregulated in an ROS-dependent manner. Furthermore, pretreatment with ATM and p53 inhibitors (KU55933 and Pifithrin-α) could reduce the occurrence of G2/M cell cycle arrest by inhibiting the activation of the ATM-p53 pathway. Taken together, these results indicate that ROS-mediated oxidative stress plays a key role in PLB-induced G2/M cell cycle arrest mediated by the ATM-p53 pathway. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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13 pages, 1759 KiB

Open AccessArticle

Impairment of Nucleolin Activity and Phosphorylation by a Trachylobane Diterpene from Psiadia punctulata in Cancer Cells

by Maria Laura Bellone, Lorenzo Fiengo, Carmen Cerchia, Roberta Cotugno, Ammar Bader, Antonio Lavecchia, Nunziatina De Tommasi and Fabrizio Dal Piaz

Int. J. Mol. Sci. 2022, 23(19), 11390; https://doi.org/10.3390/ijms231911390 - 27 Sep 2022

Cited by 4 | Viewed by 3041

Abstract

Human nucleolin (hNcl) is a multifunctional protein involved in the progression of various cancers and plays a key role in other pathologies. Therefore, there is still unsatisfied demand for hNcl modulators. Recently, we demonstrated that the plant ent-kaurane diterpene oridonin inhibits hNcl but, [...] Read more.

Human nucleolin (hNcl) is a multifunctional protein involved in the progression of various cancers and plays a key role in other pathologies. Therefore, there is still unsatisfied demand for hNcl modulators. Recently, we demonstrated that the plant ent-kaurane diterpene oridonin inhibits hNcl but, unfortunately, this compound is quite toxic for healthy cells. Trachylobane diterpene 6,19-dihydroxy-ent-trachiloban-17-oic acid (compound 12) extracted from Psiadia punctulata (DC.) Vatke (Asteraceae) emerged as a ligand of hNcl from a cellular thermal shift assay (CETSA)-based screening of a small library of diterpenes. Effective interaction between this compound and the protein was demonstrated to occur both in vitro and inside two different types of cancer cells. Based on the experimental and computational data, a model of the hNcl/compound 12 complex was built. Because of this binding, hNcl mRNA chaperone activity was significantly reduced, and the level of phosphorylation of the protein was affected. At the biological level, cancer cell incubation with compound 12 produced a cell cycle block in the subG0/G1 phase and induced early apoptosis, whereas no cytotoxicity towards healthy cells was observed. Overall, these results suggested that 6,19-dihydroxy-ent-trachiloban-17-oic could represent a selective antitumoral agent and a promising lead for designing innovative hNcl inhibitors also usable for therapeutic purposes. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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16 pages, 1656 KiB

Open AccessArticle

Evaluation of the Sensitivity of Breast Cancer Cell Lines to Cardiac Glycosides Unveils ATP1B3 as a Possible Biomarker for the Personalized Treatment of ERα Expressing Breast Cancers

by Filippo Acconcia

Int. J. Mol. Sci. 2022, 23(19), 11102; https://doi.org/10.3390/ijms231911102 - 21 Sep 2022

Cited by 2 | Viewed by 1996

Abstract

The molecular classification of breast cancer (BC) dictates pharmacological treatment. Estrogen receptor α (ERα) expressing tumors are treated with 4OH-tamoxifen or fulvestrant, which inhibits the receptor, or with aromatase inhibitors (i.e., anastrozole, letrozole, and exemestane) that reduce the 17β-estradiol (E2) circulating blood levels. [...] Read more.

The molecular classification of breast cancer (BC) dictates pharmacological treatment. Estrogen receptor α (ERα) expressing tumors are treated with 4OH-tamoxifen or fulvestrant, which inhibits the receptor, or with aromatase inhibitors (i.e., anastrozole, letrozole, and exemestane) that reduce the 17β-estradiol (E2) circulating blood levels. Besides such endocrine therapy (ET) drugs, ERα-positive BCs can be treated with epidermal growth factor receptor (EGF-R) inhibitors (i.e., gefitinib, erlotinib, and lapatinib) according to HER2 expression. Notwithstanding these anti-BC drugs, novel personalized approaches for BC treatment are required because prolonged administration of those pharmaceutics determines resistant phenotypes, which result in metastatic BC. We have recently reported that the cardiac glycoside (CG) (i.e., Na/K ATPase inhibitor) ouabain could be repurposed for ERα-positive primary and metastatic BC treatment as it induces ERα degradation and kills BC cells. Here, we evaluated if other CGs could represent additional treatment options for ERα-positive BCs and if the Na/K ATPase could be considered a biomarker for ERα-positive BC treatment. The results indicate that the ATP1B3 Na/K ATPase isoform can educate the choice for the personalized treatment of ERα-positive BC with CGs and that CGs could be more efficacious if they are administered in association with gefitinib. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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25 pages, 4990 KiB

Open AccessArticle

Isoquinoline Alkaloids from Coptis chinensis Franch: Focus on Coptisine as a Potential Therapeutic Candidate against Gastric Cancer Cells

by Sylwia Nakonieczna, Aneta Grabarska, Kinga Gawel, Paula Wróblewska-Łuczka, Arkadiusz Czerwonka, Andrzej Stepulak and Wirginia Kukula-Koch

Int. J. Mol. Sci. 2022, 23(18), 10330; https://doi.org/10.3390/ijms231810330 - 7 Sep 2022

Cited by 22 | Viewed by 3400

Abstract

Gastric cancer (GC) has high incidence rates and constitutes a common cause of cancer mortality. Despite advances in treatment, GC remains a challenge in cancer therapy which is why novel treatment strategies are needed. The interest in natural compounds has increased significantly in [...] Read more.

Gastric cancer (GC) has high incidence rates and constitutes a common cause of cancer mortality. Despite advances in treatment, GC remains a challenge in cancer therapy which is why novel treatment strategies are needed. The interest in natural compounds has increased significantly in recent years because of their numerous biological activities, including anti-cancer action. The isolation of the bioactive compounds from Coptis chinensis Franch was carried out with the Centrifugal Partition Chromatography (CPC) technique, using a biphasic solvent system composed of chloroform (CHCl₃)—methanol (MeOH)—water (H₂O) (4:3:3, v/v) with an addition of hydrochloric acid and trietylamine. The identity of the isolated alkaloids was confirmed using a high resolution HPLC-MS chromatograph. The phytochemical constituents of Coptis chinensis such as berberine, jatrorrhizine, palmatine and coptisine significantly inhibited the viability and growth of gastric cancer cell lines ACC-201 and NCI-N87 in a dose-dependent manner, with coptisine showing the highest efficacy as revealed using MTT and BrdU assays, respectively. Flow cytometry analysis confirmed the coptisine-induced population of gastric cancer cells in sub-G1 phase and apoptosis. The combination of coptisine with cisplatin at the fixed-ratio of 1:1 exerted synergistic and additive interactions in ACC-201 and NCI-N87, respectively, as determined by means of isobolographic analysis. In in vivo assay, coptisine was safe for developing zebrafish at the dose equivalent to the highest dose active in vitro, but higher doses (greater than 10 times) caused morphological abnormalities in larvae. Our findings provide a theoretical foundation to further studies on more detailed mechanisms of the bioactive compounds from Coptis chinensis Franch anti-cancer action that inhibit GC cell survival in in vitro settings. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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15 pages, 1722 KiB

Open AccessArticle

Anticancer and Antioxidant Activities in Ganoderma lucidum Wild Mushrooms in Poland, as Well as Their Phenolic and Triterpenoid Compounds

by Joanna Kolniak-Ostek, Jan Oszmiański, Anna Szyjka, Helena Moreira and Ewa Barg

Int. J. Mol. Sci. 2022, 23(16), 9359; https://doi.org/10.3390/ijms23169359 - 19 Aug 2022

Cited by 39 | Viewed by 4676

Abstract

The goal of this study was to the assess anti-cancer and antioxidant properties of the Ganoderma lucidum fruiting body, and to identify bioactive compounds found in their extracts. Significant antiproliferative activity was observed against MCF-7, MCF-7/DX, LOVO, LOVO/DX, MDA-MB 231, SW 620, and [...] Read more.

The goal of this study was to the assess anti-cancer and antioxidant properties of the Ganoderma lucidum fruiting body, and to identify bioactive compounds found in their extracts. Significant antiproliferative activity was observed against MCF-7, MCF-7/DX, LOVO, LOVO/DX, MDA-MB 231, SW 620, and NHDF cell lines. With IC₅₀ values of 25.38 µg/mL and 47.90 µg/mL, respectively, the extract was most effective against MDA-MB 231 and SW 620 cell lines. The bioactive compounds were identified using an ACQUITY UPLC-PDA-MS system. The extracts contained 13 triterpenoids and 28 polyphenols from the flavonols, phenolic acids, flavones, flavan-3-ols, and stilbenes families. Ganoderic acid derivative was found to be the most abundant triterpenoid (162.4 mg/g DW), followed by ganoderic acid B (145.6 mg/g DW). Resveratrol was the most abundant phenolic in the extract (5155.7 mg/100 g DM). The findings could explain why G. lucidum extracts are used in folk medicine. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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19 pages, 3457 KiB

Open AccessArticle

Aspiletrein A Induces Apoptosis Cell Death via Increasing Reactive Oxygen Species Generation and AMPK Activation in Non-Small-Cell Lung Cancer Cells

by Wasita Witayateeraporn, Hien Minh Nguyen, Duc Viet Ho, Hoai Thi Nguyen, Pithi Chanvorachote, Chanida Vinayanuwattikun and Varisa Pongrakhananon

Int. J. Mol. Sci. 2022, 23(16), 9258; https://doi.org/10.3390/ijms23169258 - 17 Aug 2022

Cited by 3 | Viewed by 2337

Abstract

Lung cancer remains a leading cause of death in cancer patients, and deregulation of apoptosis is a serious concern in clinical practice, even though therapeutic intervention has been greatly improved. Plants are a versatile source of biologically active compounds for anticancer drug discovery, [...] Read more.

Lung cancer remains a leading cause of death in cancer patients, and deregulation of apoptosis is a serious concern in clinical practice, even though therapeutic intervention has been greatly improved. Plants are a versatile source of biologically active compounds for anticancer drug discovery, and aspiletrein A (AA) is a steroidal saponin isolated from Aspidistra letreae that has a potent cytotoxic effect on various cancer cell lines. In this study, we investigated and determined the underlying molecular mechanism by which AA induces apoptosis. AA strongly induced apoptosis in NSCLC cells by mediating ROS generation and thereby activating AMP-activated protein kinase (AMPK) signaling. Consequently, downstream signaling and levels of phosphorylated mTOR and Bcl-2 were significantly decreased. Pretreatment with either an antioxidant, N-acetylcysteine, or an AMPK inhibitor, compound C, could reverse the apoptosis-inducing effect and counteract the effect of AA on the AMPK signaling pathway. Decreased levels of Bcl-2 were due to AA-mediating Bcl-2 degradation via a ROS/AMPK/mTOR axis-dependent proteasomal mechanism. Consistently, the apoptotic-inducing effect of AA was also observed in patient-derived malignant lung cancer cells, and it suppressed an in vitro 3D-tumorigenesis. This study identified the underlying mechanism of AA on lung cancer apoptosis, thereby facilitating potential research and development of this compound for further clinical implications. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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19 pages, 4346 KiB

Open AccessArticle

Pharmacological and In Silico Analysis of Oat Avenanthramides as EGFR Inhibitors: Effects on EGF-Induced Lung Cancer Cell Growth and Migration

by Lorenza Trabalzini, Jasmine Ercoli, Alfonso Trezza, Irene Schiavo, Giulia Macrì, Andrea Moglia, Ottavia Spiga and Federica Finetti

Int. J. Mol. Sci. 2022, 23(15), 8534; https://doi.org/10.3390/ijms23158534 - 1 Aug 2022

Cited by 9 | Viewed by 2852

Abstract

Avena sativa L. is a wholegrain cereal and an important edible crop. Oats possesses high nutritional and health promoting values and contains high levels of bioactive compounds, including a group of phenolic amides, named avenanthramides (Avns), exerting antioxidant, anti-inflammatory, and anticancer activities. Epidermal [...] Read more.

Avena sativa L. is a wholegrain cereal and an important edible crop. Oats possesses high nutritional and health promoting values and contains high levels of bioactive compounds, including a group of phenolic amides, named avenanthramides (Avns), exerting antioxidant, anti-inflammatory, and anticancer activities. Epidermal growth factor receptor (EGFR) represents one of the most known oncogenes and it is frequently up-regulated or mutated in human cancers. The oncogenic effects of EGFR include enhanced cell growth, angiogenesis, and metastasis, and down-regulation or inhibition of EGFR signaling has therapeutic benefit. Front-line EGFR tyrosine kinase inhibitor therapy is the standard therapy for patients with EGFR-mutated lung cancer. However, the clinical effects of EGFR inhibition may be lost after a few months of treatment due to the onset of resistance. Here, we showed the anticancer activity of Avns, focusing on EGFR activation and signaling pathway. Lung cancer cellular models have been used to evaluate the activity of Avns on tumor growth, migration, EMT, and anoikis induced by EGF. In addition, docking and molecular dynamics simulations showed that the Avns bind with high affinity to a region in the vicinity of αC-helix and the DGF motif of EGFR, jeopardizing the target biological function. Altogether, our results reveal a new pharmacological activity of Avns as EGFR tyrosine kinase inhibitors. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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Review

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11 pages, 1159 KiB

Open AccessReview

Fibres and Colorectal Cancer: Clinical and Molecular Evidence

by Francesca Celiberto, Adriana Aloisio, Bruna Girardi, Maria Pricci, Andrea Iannone, Francesco Russo, Giuseppe Riezzo, Benedetta D’Attoma, Enzo Ierardi, Giuseppe Losurdo and Alfredo Di Leo

Int. J. Mol. Sci. 2023, 24(17), 13501; https://doi.org/10.3390/ijms241713501 - 31 Aug 2023

Cited by 7 | Viewed by 3447

Abstract

Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which is most influenced by dietary habits. In Western countries, an [...] Read more.

Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which is most influenced by dietary habits. In Western countries, an inadequate dietary intake of fibers is endemic, and this could be a driving factor in the increase of CRC incidence. Indeed, several epidemiologic studies have elucidated an inverse relationship between daily fiber intake and risk of CRC. Long-term prognosis in CRC survivors is also dependent on dietary fibers. Several pathogenetic mechanisms may be hypothesized. Fibers may interfere with the metabolism of bile acids, which may promote colon carcinogenesis. Further, fibers are often contained in vegetables which, in turn, contain large amounts of antioxidant agents like resveratrol, polyphenols, or phytoestrogens. Moreover, fibers can be digested by commensal flora, thus producing compounds such as butyrate, which exerts an antiproliferative effect. Finally, fibers may modulate gut microbiota, whose composition has shown to be associated with CRC onset. In this regard, dietary interventions based on high-fiber-containing diets are ongoing to prevent CRC development, especially in patients with high potential for this type of tumor. Despite the fact that outcomes are preliminary, encouraging results have been observed. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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49 pages, 6590 KiB

Open AccessReview

Anticancer Potential of Natural Chalcones: In Vitro and In Vivo Evidence

by Radka Michalkova, Ladislav Mirossay, Martin Kello, Gabriela Mojzisova, Janette Baloghova, Anna Podracka and Jan Mojzis

Int. J. Mol. Sci. 2023, 24(12), 10354; https://doi.org/10.3390/ijms241210354 - 19 Jun 2023

Cited by 16 | Viewed by 2497

Abstract

There is no doubt that significant progress has been made in tumor therapy in the past decades. However, the discovery of new molecules with potential antitumor properties still remains one of the most significant challenges in the field of anticancer therapy. Nature, especially [...] Read more.

There is no doubt that significant progress has been made in tumor therapy in the past decades. However, the discovery of new molecules with potential antitumor properties still remains one of the most significant challenges in the field of anticancer therapy. Nature, especially plants, is a rich source of phytochemicals with pleiotropic biological activities. Among a plethora of phytochemicals, chalcones, the bioprecursors of flavonoid and isoflavonoids synthesis in higher plants, have attracted attention due to the broad spectrum of biological activities with potential clinical applications. Regarding the antiproliferative and anticancer effects of chalcones, multiple mechanisms of action including cell cycle arrest, induction of different forms of cell death and modulation of various signaling pathways have been documented. This review summarizes current knowledge related to mechanisms of antiproliferative and anticancer effects of natural chalcones in different types of malignancies including breast cancers, cancers of the gastrointestinal tract, lung cancers, renal and bladder cancers, and melanoma. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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26 pages, 1427 KiB

Open AccessReview

The Involvement of Natural Polyphenols in Molecular Mechanisms Inducing Apoptosis in Tumor Cells: A Promising Adjuvant in Cancer Therapy

by Adele Chimento, Arianna De Luca, Maria D’Amico, Francesca De Amicis and Vincenzo Pezzi

Int. J. Mol. Sci. 2023, 24(2), 1680; https://doi.org/10.3390/ijms24021680 - 14 Jan 2023

Cited by 25 | Viewed by 3562

Abstract

Various literature data show how a diet rich in vegetables could reduce the incidence of several cancers due to the contribution of the natural polyphenols contained in them. Polyphenols are attributed multiple pharmacological actions such as anti-inflammatory, anti-oxidant, antibiotic, antiseptic, anti-allergic, cardioprotective and [...] Read more.

Various literature data show how a diet rich in vegetables could reduce the incidence of several cancers due to the contribution of the natural polyphenols contained in them. Polyphenols are attributed multiple pharmacological actions such as anti-inflammatory, anti-oxidant, antibiotic, antiseptic, anti-allergic, cardioprotective and even anti-tumor properties. The multiple mechanisms involved in their anti-tumor action include signaling pathways modulation associated with cell proliferation, differentiation, migration, angiogenesis, metastasis and cell death. Since the dysregulation of death processes is involved in cancer etiopathology, the natural compounds able to kill cancer cells could be used as new anticancer agents. Apoptosis, a programmed form of cell death, is the most potent defense against cancer and the main mechanism used by both chemotherapy agents and polyphenols. The aim of this review is to provide an update of literature data on the apoptotic molecular mechanisms induced by some representative polyphenol family members in cancer cells. This aspect is particularly important because it may be useful in the design of new therapeutic strategies against cancer involving the polyphenols as adjuvants. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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22 pages, 1707 KiB

Open AccessReview

Potential Focal Adhesion Kinase Inhibitors in Management of Cancer: Therapeutic Opportunities from Herbal Medicine

by Feiyu Chen, Zhangfeng Zhong, Cheng Zhang, Yuanjun Lu, Yau-Tuen Chan, Ning Wang, Di Zhao and Yibin Feng

Int. J. Mol. Sci. 2022, 23(21), 13334; https://doi.org/10.3390/ijms232113334 - 1 Nov 2022

Cited by 2 | Viewed by 3503

Abstract

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and [...] Read more.

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and studies have revealed its biological behavior in tumor cell proliferation, migration, and adhesion. Herein we provide an overview of the complex biology of the FAK family members and their context-dependent nature. Next, with a focus on cancer, we highlight the activities of FAK signaling in different types of cancer and how knowledge of them is being used for screening natural compounds used in herbal medicine to fight tumor development. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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16 pages, 843 KiB

Open AccessReview

Green Tea Catechins: Nature’s Way of Preventing and Treating Cancer

by Mohd Farhan

Int. J. Mol. Sci. 2022, 23(18), 10713; https://doi.org/10.3390/ijms231810713 - 14 Sep 2022

Cited by 71 | Viewed by 12393

Abstract

Green tea’s (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Recent research demonstrates that the number of hydroxyl groups and the presence of specific structural groups have a [...] Read more.

Green tea’s (Camellia sinensis) anticancer and anti-inflammatory effects are well-known. Catechins are the most effective antioxidants among the physiologically active compounds found in Camellia sinesis. Recent research demonstrates that the number of hydroxyl groups and the presence of specific structural groups have a substantial impact on the antioxidant activity of catechins. Unfermented green tea is the finest source of these chemicals. Catechins have the ability to effectively neutralize reactive oxygen species. The catechin derivatives of green tea include epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). EGCG has the greatest anti-inflammatory and anticancer potential. Notably, catechins in green tea have been explored for their ability to prevent a variety of cancers. Literature evidence, based on epidemiological and laboratory studies, indicates that green tea catechins have certain properties that can serve as the basis for their consideration as lead molecules in the synthesis of novel anticancer drugs and for further exploration of their role as pharmacologically active natural adjuvants to standard chemotherapeutics. The various sections of the article will focus on how catechins affect the survival, proliferation, invasion, angiogenesis, and metastasis of tumors by modulating cellular pathways. Full article

(This article belongs to the Special Issue Natural Compounds in Cancer Therapy and Prevention)

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