Antitumor Activity of Natural Products and Related Compounds—2nd Edition

Topic Information

Dear Colleagues,

Cancer is one of the leading causes of morbidity and mortality in humans today, and the number of people affected by cancer is growing. As a result, the search for new antitumor agents that may be more effective and secure than existing treatments is an ongoing effort.

Nature provides a wide range of compounds with a great variety of chemical scaffolds and distinct bioactivity profiles. Indeed, natural products are a rich source of bioactive molecules that, over the years, have found application in the treatment of many diseases, including cancer. Natural products have played an important role in chemotherapy and chemoprevention by providing antitumor drugs, such as camptothecin, doxorubicin, paclitaxel, vinblastine, and vincristine, as well as in understanding the cellular and molecular mechanisms underlying antitumor activity. Significant advances in natural source isolation and extraction techniques have enabled the identification of novel lead compounds as useful starting points for the generation of optimized molecules with enhanced therapeutic potential via semi-synthetic or synthetic processes.

The focus of this Topic is on natural substances derived from plants or animals, as well as their synthetic derivatives, which have been investigated for their ability to counteract cancer progression.

Dr. Barbara De Filippis
Dr. Alessandra Ammazzalorso
Dr. Marialuigia Fantacuzzi
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomolecules biomolecules	4.8	9.4	2011	16.3 Days	CHF 2700	Submit
Cancers cancers	4.5	8.0	2009	16.3 Days	CHF 2900	Submit
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900	Submit
Molecules molecules	4.2	7.4	1996	15.1 Days	CHF 2700	Submit
Scientia Pharmaceutica scipharm	2.3	4.6	1930	31.4 Days	CHF 1000	Submit
Pharmaceutics pharmaceutics	4.9	7.9	2009	14.9 Days	CHF 2900	Submit

MDPI Topics is cooperating with Preprints.org and has built a direct connection between MDPI journals and Preprints.org. Authors are encouraged to enjoy the benefits by posting a preprint at Preprints.org prior to publication:

1. Immediately share your ideas ahead of publication and establish your research priority;
2. Protect your idea from being stolen with this time-stamped preprint article;
3. Enhance the exposure and impact of your research;
4. Receive feedback from your peers in advance;
5. Have it indexed in Web of Science (Preprint Citation Index), Google Scholar, Crossref, SHARE, PrePubMed, Scilit and Europe PMC.

Published Papers (8 papers)

Order results

Content type Publication Date

Result details

Normal Extended Compact

Journals

All Biomolecules Cancers IJMS Molecules Sci. Pharm. Pharmaceutics

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

Error

Oops... you haven't selected anything for export.

Ok

clear

attachment

Supplementary material:
Supplementary File 1 (ZIP, 2039 KiB)

13 pages, 4806 KiB  

Open AccessArticle

Okanin Inhibits Cell Growth and Induces Apoptosis and Pyroptosis in Oral Cancer

by Wei-Tso Chia, Kuei-Yuan Chen, Cheng-Yu Yang, Cheng-Chih Hsieh, Chang-Huei Tsao, Chih-Kung Lin, Bo Peng, Sien-Lin Ho, Yi-Ling Chen, Szu-Chien Chang and Yuan-Wu Chen

Cancers 2024, 16(18), 3195; https://doi.org/10.3390/cancers16183195 - 19 Sep 2024

Viewed by 756

Abstract

Background: Okanin, a flavonoid compound derived from Bidens pilosa L., has garnered attention for its anti-inflammatory properties. Although Bidens pilosa is commonly used in healthcare products and functional foods, the anticancer potential of okanin, particularly in oral cancer, remains underexplored. This study aims [...] Read more.

Background: Okanin, a flavonoid compound derived from Bidens pilosa L., has garnered attention for its anti-inflammatory properties. Although Bidens pilosa is commonly used in healthcare products and functional foods, the anticancer potential of okanin, particularly in oral cancer, remains underexplored. This study aims to investigate the effects of okanin on oral cancer cell lines and its potential as a therapeutic agent. Methods: The study involved assessing the cytotoxic effects of okanin on oral cancer cell lines SAS, SCC25, HSC3, and OEC-M1. The IC50 values were determined using methylene blue assays, and the clonogenic capacity was evaluated through colony formation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis. Caspase-3/7 activity assays and annexin V/7-AAD staining confirmed the induction of apoptosis and pyroptosis. In vivo efficacy was assessed using a SAS xenograft model, and immunohistochemical analysis of xenograft tissue was performed to examine pyroptosis-related markers. Results: Okanin exhibited potent cytotoxic effects with IC50 values of 12.0 ± 0.8, 58.9 ± 18.7, 18.1 ± 5.3, and 43.2 ± 6.2 μM in SAS, SCC25, HSC3, and OEC-M1 cells, respectively. It caused dose- and time-dependent reductions in cell viability and significantly impaired clonogenic capacity. Flow cytometry revealed G2/M cell cycle arrest and increased sub-G1 population, indicating cell cycle disruption and death. Okanin induced both apoptosis and pyroptosis, as confirmed by caspase-3/7 activity and annexin V/7-AAD staining. In vivo, okanin reduced tumor growth and involved pyroptosis-related markers such as CASP1, GSDMC, GSDMD, and GSDME. Conclusions: Okanin demonstrates significant anticancer potential, particularly in oral cancer, by inducing both apoptosis and pyroptosis. Its efficacy in reducing tumor growth in vivo further supports its potential as a novel therapeutic option. Further mechanistic studies are needed to elucidate the pathways involved in okanin-mediated cell death and to explore its clinical applications. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 112 KiB)

15 pages, 2344 KiB  

Open AccessArticle

The Cytotoxic Activity and Metabolic Profiling of Hyptis rhomboidea Mart. et Gal

by Jian Zhang, Wenjie Gao, Israt Jahan, Run Zhai, Kaiwei Yao, Jian Yan and Ping Li

Molecules 2024, 29(17), 4216; https://doi.org/10.3390/molecules29174216 - 5 Sep 2024

Viewed by 684

Abstract

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat [...] Read more.

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography–mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC₅₀ values ranging from 15.8 to 40.0 μg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph–mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 3668 KiB)

16 pages, 5003 KiB  

Open AccessArticle

Alkaloid-Based Isoxazolylureas: Synthesis and Effect in Combination with Anticancer Drugs on C6 Rat Glioma Model Cells

by Gulim K. Mukusheva, Roza I. Jalmakhanbetova, Altynay Zh. Shaibek, Manshuk S. Nurmaganbetova, Aigerym R. Zhasymbekova, Oralgazy A. Nurkenov, Ekaterina A. Akishina, Irina A. Kolesnik, Evgenij A. Dikusar, Tatiana I. Terpinskaya, Vladimir A. Kulchitsky, Vladimir I. Potkin, Alexander L. Pushkarchuk, Dmitry A. Lyakhov and Dominik L. Michels

Molecules 2024, 29(14), 3246; https://doi.org/10.3390/molecules29143246 - 9 Jul 2024

Viewed by 958

Abstract

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, [...] Read more.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Graphical abstract

20 pages, 4271 KiB  

Open AccessArticle

3,5-DCQA as a Major Molecule in MeJA-Treated Dendropanax morbifera Adventitious Root to Promote Anti-Lung Cancer and Anti-Inflammatory Activities

by Fengjiao Xu, Anjali Kariyarath Valappil, Shaojian Zheng, Bingsong Zheng, Deokchun Yang and Qiang Wang

Biomolecules 2024, 14(6), 705; https://doi.org/10.3390/biom14060705 - 15 Jun 2024

Cited by 2 | Viewed by 1229

Abstract

(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production [...] Read more.

(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production in DMAR, optimizing concentration and exposure time for cost-effectiveness. We also assessed its anti-inflammatory and anti-lung cancer activities and related gene expression levels. (3) Results: MeJA treatment significantly increased the production of the phenolic compound 3,5-Di-caffeoylquinic acid (3,5-DCQA). The maximum 3,5-DCQA production was achieved with a MeJA treatment at 40 µM for 36 h. MeJA-DMARE displayed exceptional anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-induced RAW 264.7 cells. Moreover, it downregulated the mRNA expression of key inflammation-related cytokines. Additionally, MeJA-DMARE exhibited anti-lung cancer activity by promoting ROS production in A549 lung cancer cells and inhibiting its migration. It also modulated apoptosis in lung cancer cells via the Bcl-2 and p38 MAPK pathways. (4) Conclusions: MeJA-treated DMARE with increased 3,5-DCQA production holds significant promise as a sustainable and novel material for pharmaceutical applications thanks to its potent antioxidant, anti-inflammatory, and anti-lung cancer properties. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 52 KiB)

16 pages, 8312 KiB  

Open AccessArticle

Temporin-GHaK Exhibits Antineoplastic Activity against Human Lung Adenocarcinoma by Inhibiting the Wnt Signaling Pathway through miRNA-4516

by Yueli Liu, Hui Liu, Jiaxin Zhang and Yingxia Zhang

Molecules 2024, 29(12), 2797; https://doi.org/10.3390/molecules29122797 - 12 Jun 2024

Viewed by 896

Abstract

(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. [...] Read more.

(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. (2) Methods: The cell viability, migration, invasion, apoptosis, and cell cycle of A549 and PC-9 cells were tested after GHaK treatment. miRNA sequencing, RT-PCR, Western blotting, and luciferase reporter gene assay were further performed to reveal the potential mechanism. (3) Results: GHaK significantly suppressed cell viability, migration, and invasion; induced apoptosis; and caused cell cycle arrest in the G2/M and S phase in PC-9 and A549 cells, respectively. The miRNA sequencing results show a total of 161 up-regulated and 115 down-regulated miRNAs. Furthermore, the study identified six up-regulated miRNAs (miR-4516, miR-4284, miR-204-5p, miR-12136, miR-4463, and miR-1296-3p) and their inhibitory effects on the expressions of target genes (Wnt 8B, FZD2, DVL3, and FOSL1) caused by miR-4516 directly interacting with Wnt 8B. Western blotting revealed the down-regulation of p-GSK-3β, along with a decreased expressions of cyclin A1 and CDK2 in A549 cells and cyclin B1 and CDK1 in PC-9 cells. (4) Conclusions: Temporin-GHaK exhibits antineoplastic activity against human lung adenocarcinoma by inhibiting the Wnt signaling pathway through miRNA-4516. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 901 KiB)

22 pages, 3368 KiB  

Open AccessArticle

General Direct Anticancer Effects of Deer Growing Antler Extract in Several Tumour Cell Lines, and Immune System-Mediated Effects in Xenograft Glioblastoma

by Alessandra Rossetti, Louis Chonco, Nicolas Alegría, Veronica Zelli, Andrés J. García, Carmen Ramírez-Castillejo, Alessandra Tessitore, Carlos de Cabo, Tomás Landete-Castillejos and Claudio Festuccia

Pharmaceutics 2024, 16(5), 610; https://doi.org/10.3390/pharmaceutics16050610 - 30 Apr 2024

Viewed by 2618

Abstract

Deer antlers are the fastest growing tissue. Because they are based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus their extract (DVA) is effective also against the few human tumours studied so far. We assessed whether [...] Read more.

Deer antlers are the fastest growing tissue. Because they are based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus their extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound by testing the direct effects in cells of different tumours: glioblastoma (GBM; lines U87MG and U251), colorectal (CRC; lines DLD-1, HT-29, SW480, and SW620), breast cancer (BRCA; lines MCF7, SKBR3, and PA00), and leukaemia (THP-1). DVA reduced the viability of tumours but not healthy cells (NHC; lines 293T and HaCaT). Mobility decreased at least for the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight by 66.3% and 61.4% respectively, and it also reduced spleen weight (43.8%). In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related to tumour fighting and down-regulated those related to inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system. DVA may contain a future anticancer medicine without secondary effects. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 776 KiB)

15 pages, 5364 KiB  

Open AccessArticle

Synergistic Anti-Cancer Effects of ERB-041 and Genistein through Estrogen Receptor Suppression-Mediated PI3K/AKT Pathway Downregulation in Canine Mammary Gland Tumor Cells

by Min-Jae Yoo, Ye-Ji Jang, Sang-Youel Park, Ja-Wun Choi and Jae-Won Seol

Int. J. Mol. Sci. 2024, 25(5), 2466; https://doi.org/10.3390/ijms25052466 - 20 Feb 2024

Cited by 1 | Viewed by 1804

Abstract

Canine-mammary-gland tumors (CMTs) are prevalent in female dogs, with approximately 50% of them being malignant and often presenting as inoperable owing to their size or metastasis. Owing to poor outcomes, effective alternatives to conventional chemotherapy for humans are necessary. Two estrogen receptors, estrogen [...] Read more.

Canine-mammary-gland tumors (CMTs) are prevalent in female dogs, with approximately 50% of them being malignant and often presenting as inoperable owing to their size or metastasis. Owing to poor outcomes, effective alternatives to conventional chemotherapy for humans are necessary. Two estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), which act in opposition to each other, are involved, and CMT growth involves ERα through the phosphoinositide 3-kinases (PI3K)/AKT pathway. In this study, we aimed to identify the synergistic anti-cancer effects of ERB-041, an ERβ agonist, and genistein, an isoflavonoid from soybeans known to have ERβ-specific pseudo-estrogenic actions, on CMT-U27 and CF41.Mg CMT cell lines. ERB-041 and genistein synergistically inhibited cell proliferation and increased the number of annexin V-positive cells in both cell lines. Furthermore, we observed a synergistic increase in the Bax/Bcl-2 ratio and cleaved caspase-3 expression. Additionally, cell-cycle arrest occurred through the synergistic regulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). We also found a synergistic decrease in the expression of ERα, and the expression of proteins involved in the PI3K/AKT pathway, including p-PI3K, phosphatase and tensin homolog (PTEN), AKT, and mechanistic target of rapamycin (mTOR). In conclusion, ERB-041 and genistein exhibited a synergistic anticancer effect on CMTs, suggesting that cotreatment with ERB-041 and genistein is a promising treatment for CMTs. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 2167 KiB)

14 pages, 4297 KiB  

Open AccessArticle

The Use of Schisandrin B to Combat Triple-Negative Breast Cancers by Inhibiting NLRP3-Induced Interleukin-1β Production

by Chun-Ming Chang, Ting-Ruei Liang and Ho Yin Pekkle Lam

Biomolecules 2024, 14(1), 74; https://doi.org/10.3390/biom14010074 - 5 Jan 2024

Cited by 3 | Viewed by 1975

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive and fatal breast cancer subtype. Nowadays, chemotherapy remains the standard treatment of TNBC, and immunotherapy has emerged as an important alternative. However, the high rate of TNBC recurrence suggests that new treatment is desperately needed. [...] Read more.

Triple-negative breast cancer (TNBC) is the most aggressive and fatal breast cancer subtype. Nowadays, chemotherapy remains the standard treatment of TNBC, and immunotherapy has emerged as an important alternative. However, the high rate of TNBC recurrence suggests that new treatment is desperately needed. Schisandrin B (Sch B) has recently revealed its anti-tumor effects in cancers such as cholangiocarcinoma, hepatoma, glioma, and multi-drug-resistant breast cancer. However, there is still a need to investigate using Sch B in TNBC treatment. Interleukin (IL)-1β, an inflammatory cytokine that can be expressed and produced by the cancer cell itself, has been suggested to promote BC proliferation and progression. In the current study, we present evidence that Sch B can significantly suppress the growth, migration, and invasion of TNBC cell lines and patient-derived TNBC cells. Through inhibition of inflammasome activation, Sch B inhibits interleukin (IL)-1β production of TNBC cells, hindering its progression. This was confirmed using an NLRP3 inhibitor, OLT1177, which revealed a similar beneficial effect in combating TNBC progression. Sch B treatment also inhibits IL-1β-induced EMT expression of TNBC cells, which may contribute to the anti-tumor response. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

 

Error

Oops... you haven't selected anything for export.

Ok

clear

Displaying articles 1-8