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Advances in Plant-Sourced Natural Compounds as Anticancer Agents
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Advances in Plant-Sourced Natural Compounds as Anticancer Agents

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 9614

Special Issue Editors

Dr. Violeta Popovici

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Guest Editor
Agro-Forestry and Biodiversity Laboratory, Natural Parks and Protected Areas, “Costin C. Kiriţescu” National Institute of Economic Research—Center for Mountain Economics (INCE-CEMONT) of Romanian Academy, 725700 Vatra Dornei, Romania
Interests: plant/lichen secondary metabolites-identification and pharmacological potential; antibiotics; antimicrobial activity; in vitro anticancer activity; oral cancer; ROS; oxidative stress; antioxidants/pro-oxidants
Special Issues, Collections and Topics in MDPI journals
Dr. Emma Adriana Ozon

E-Mail Website
Guest Editor
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania
Interests: drug design; development, optimization, and manufacturing of pharmaceutical products; pre- and post-compression parameters for solid dosage forms; preformulating studies on pharmaceuticals; physico-chemical characterization of materials; cyclodextrin inclusion complexes; drug delivery systems; pharmaceutical processes; drug release profiles; quality of pharmaceutical forms
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Cerasela Elena Gîrd

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Guest Editor
Department of Pharmacognosy, Phytochemistry and Phytotherapy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Interests: plant extracts; pharmacognosy; phytochemical analyses; antioxidant activity; phytotherapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. ‪Dumitru Lupuliasa

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Guest Editor
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 020956 Bucharest, Romania
Interests: pharmaceutical forms manufacturing; drug preformulation and formulation; drug release; biopharmaceutical charcterization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is among the leading causes of death worldwide. Generally, cancer rates are highest in countries whose populations have the highest life expectancy, education level, and standard of living. The principal purpose of current cancer therapy is to perturb or kill the malignant cells from early-stage neoplasms or those remaining after surgery without affecting the normal cytophysiological processes, and to trigger the immunity defense against the residual tumor cells. Natural products are rich sources of bioactive molecules for new anticancer drugs. Phytochemicals show great potential in improving the clinical condition of cancer patients, as demonstrated by numerous preclinical and clinical studies. Plant-sourced natural compounds have diverse biological activities, including antioxidant and anticancer effects. Recently, many emerging studies revealed the uses of plant-sourced natural compounds and individual anticancer drugs that could be promising combinations in hampering multiple signaling pathways involved in cancer development and progression. In addition to enhancing the therapeutic efficacy, this has also been proven to reduce the dosage of chemotherapeutic drugs, overcoming multiple drug resistance and minimizing treatment side effects. This Special Issue focuses on recent research regarding plant-sourced natural compounds with anticancer activity through various mechanisms and novel pharmaceutical formulations with potential applications in prophylaxis and the treatment of neoplasia.

Dr. Violeta Popovici
Dr. Emma Adriana Ozon
Prof. Dr. Cerasela Elena Gîrd
Prof. Dr. ‪Dumitru Lupuliasa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • medicinal plants
  • natural compounds
  • phytochemicals
  • antioxidant activity
  • anticancer activity
  • phytotherapy
  • drug discovery
  • drug delivery
  • pharmaceutical formulation

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Published Papers (5 papers)

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Research

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15 pages, 5198 KiB  
Article
Evaluation of Antiproliferative Potentials Associated with the Volatile Compounds of Lantana camara Flowers: Selective In Vitro Activity
by Jennifer El Hajj, Louna Karam, Ali Jaber, Edmond Cheble, Elias Akoury, Philippe Hussein Kobeissy, José-Noel Ibrahim and Ali Yassin
Molecules 2024, 29(22), 5431; https://doi.org/10.3390/molecules29225431 - 18 Nov 2024
Viewed by 547
Abstract
Probing the chemical profiles and biological activities of medicinal plants is important for the discovery of new potent therapeutic products. Our study deciphers the chemical composition of the essential oils (EOs) obtained from three different flowers of Lantana camara and evaluates their antioxidant [...] Read more.
Probing the chemical profiles and biological activities of medicinal plants is important for the discovery of new potent therapeutic products. Our study deciphers the chemical composition of the essential oils (EOs) obtained from three different flowers of Lantana camara and evaluates their antioxidant and anticancer activities. This work represents the first study of EOs obtained from this plant and is based particularly on the difference in flower color. In addition, no other reports dealing specifically with the antitumor effects of such flower-derived EOs have been described in the literature. The collected flowers, white, pink, and orange, were extracted by hydrodistillation to yield EO1, EO2, and EO3 respectively. Gas chromatography–mass spectroscopy was primarily employed to identify the existing volatile compounds in the samples. Their antioxidant activities were screened through both DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assays and FRAP (ferric-reducing antioxidant power) assays. The antiproliferative effects were evaluated on two distinct breast cancer cell lines, MCF-7 and MDA-MB-231, and compared to a normal human breast cell line, MCF-10A, using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. All EOs showed notable antioxidant potential attributed to the active phytochemical compounds, with results being supported by a positive correlation between such activity and the total phenolic and flavonoid content. The most eminent, EO1, revealed a selective dose-dependent antiproliferative effect in both breast cancer cell lines, thus reflecting its potent role as an anticancer agent. We suggest that this highly selective activity is associated with the presence of bicyclogermacrene and epi-bicyclosesquiphellandrene in its chemical composition. Full article
(This article belongs to the Special Issue Advances in Plant-Sourced Natural Compounds as Anticancer Agents)
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23 pages, 12883 KiB  
Article
Antioxidant and Cytotoxic Properties of Berberis vulgaris (L.) Stem Bark Dry Extract
by Ionuț Mădălin Ivan, Octavian Tudorel Olaru, Violeta Popovici, Carmen Lidia Chițescu, Liliana Popescu, Emanuela Alice Luță, Elena Iuliana Ilie, Lorelei Irina Brașoveanu, Camelia Mia Hotnog, George Mihai Nițulescu, Rica Boscencu and Cerasela Elena Gîrd
Molecules 2024, 29(9), 2053; https://doi.org/10.3390/molecules29092053 - 29 Apr 2024
Cited by 1 | Viewed by 1830
Abstract
Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± [...] Read more.
Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigated B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq tannic acid/100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq chlorogenic acid/100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC, and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods. Our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and berberine—berberine sulfate hydrate (BS)—investigated on Daphnia sp. revealed significant BS toxicity after 24 h, while BVE revealed considerable toxicity after 48 h and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated in different tumor cell lines after 24 and 48 h of treatments. The MTS assay evidenced dose- and time-dependent antiproliferative activity, which was higher for BS than BVE. The strongest diminution of tumor cell viability was recorded in the breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported in the normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines. Full article
(This article belongs to the Special Issue Advances in Plant-Sourced Natural Compounds as Anticancer Agents)
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13 pages, 7137 KiB  
Article
Antitumor Mechanism and Therapeutic Potential of Cordycepin Derivatives
by Linlin Cui, Li Zhao, Guanghuan Shen, Dahai Yu, Tian Yuan, Yingyu Zhang and Bo Yang
Molecules 2024, 29(2), 483; https://doi.org/10.3390/molecules29020483 - 18 Jan 2024
Cited by 1 | Viewed by 1505
Abstract
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a–4c [...] Read more.
Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a–4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with an IC50 value of 27.57 ± 0.52 μM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway. Full article
(This article belongs to the Special Issue Advances in Plant-Sourced Natural Compounds as Anticancer Agents)
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23 pages, 4834 KiB  
Article
The Anticancer Effects of Marine Carotenoid Fucoxanthin through Phosphatidylinositol 3-Kinase (PI3K)-AKT Signaling on Triple-Negative Breast Cancer Cells
by Shade’ A. Ahmed, Patricia Mendonca, Samia S. Messeha, Ebenezer T. Oriaku and Karam F. A. Soliman
Molecules 2024, 29(1), 61; https://doi.org/10.3390/molecules29010061 - 21 Dec 2023
Viewed by 2039
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks specific targets such as estrogen, progesterone, and HER2 receptors. TNBC affects one in eight women in the United States, making up 15–20% of breast cancer cases. Patients with TNBC can [...] Read more.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks specific targets such as estrogen, progesterone, and HER2 receptors. TNBC affects one in eight women in the United States, making up 15–20% of breast cancer cases. Patients with TNBC can develop resistance to chemotherapy over time, leading to treatment failure. Therefore, finding other options like natural products is necessary for treatment. The advantages of using natural products sourced from plants as anticancer agents are that they are less toxic, more affordable, and have fewer side effects. These products can modulate several cellular processes of the tumor microenvironment, such as proliferation, migration, angiogenesis, cell cycle arrest, and apoptosis. The phosphatidyl inositol 3-kinase (PI3K)-AKT signaling pathway is an important pathway that contributes to the survival and growth of the tumor microenvironment and is associated with these cellular processes. This current study examined the anticancer effects of fucoxanthin, a marine carotenoid isolated from brown seaweed, in the MDA-MB-231 and MDA-MB-468 TNBC cell lines. The methods used in this study include a cytotoxic assay, PI3K-AKT signaling pathway PCR arrays, and Wes analysis. Fucoxanthin (6.25 µM) + TNF-α (50 ng/mL) and TNF-α (50 ng/mL) showed no significant effect on cell viability compared to the control in both MDA-MB-231 and MDA-MB-468 cells after a 24 h treatment period. PI3K-AKT signaling pathway PCR array studies showed that in TNF-α-stimulated (50 ng/mL) MDA-MB-231 and MDA-MB-468 cells, fucoxanthin (6.25 µM) modulated the mRNA expression of 12 genes, including FOXO1, RASA1, HRAS, MAPK3, PDK2, IRS1, EIF4EBP1, EIF4B, PTK2, TIRAP, RHOA, and ELK1. Additionally, fucoxanthin significantly downregulated the protein expression of IRS1, EIF4B, and ELK1 in MDA-MB-231 cells, and no change in the protein expression of EIF4B and ELK1 was shown in MDA-MB-468 cells. Fucoxanthin upregulated the protein expression of RHOA in both cell lines. The modulation of the expression of genes and proteins of the PI3K-AKT signaling pathway may elucidate fucoxanthin’s effects in cell cycle progression, apoptotic processes, migration, and proliferation, which shows that PI3K-AKT may be the possible molecular mechanism for fucoxanthin’s effects. In conclusion, the results obtained in this study elucidate fucoxanthin’s molecular mechanisms and indicate that fucoxanthin may be considered a promising candidate for breast cancer-targeted therapy. Full article
(This article belongs to the Special Issue Advances in Plant-Sourced Natural Compounds as Anticancer Agents)
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Review

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26 pages, 2480 KiB  
Review
The Extraction, Determination, and Bioactivity of Curcumenol: A Comprehensive Review
by Jie Li, Yitian Sun, Guohua Li, Chunsong Cheng, Xinbing Sui and Qibiao Wu
Molecules 2024, 29(3), 656; https://doi.org/10.3390/molecules29030656 - 30 Jan 2024
Cited by 3 | Viewed by 2470
Abstract
Curcuma wenyujin is a member of the Curcuma zedoaria (zedoary, Zingiberaceae) family, which has a long history in traditional Chinese medicine (TCM) due to its abundant biologically active constituents. Curcumenol, a component of Curcuma wenyujin, has several biological activities. At present, despite [...] Read more.
Curcuma wenyujin is a member of the Curcuma zedoaria (zedoary, Zingiberaceae) family, which has a long history in traditional Chinese medicine (TCM) due to its abundant biologically active constituents. Curcumenol, a component of Curcuma wenyujin, has several biological activities. At present, despite different pharmacological activities being reported, the clinical usage of curcumenol remains under investigation. To further determine the characteristics of curcumenol, the extraction, determination, and bioactivity of the compound are summarized in this review. Existing research has reported that curcumenol exerts different pharmacological effects in regard to a variety of diseases, including anti-inflammatory, anti-oxidant, anti-bactericidal, anti-diabetic, and anti-cancer activity, and also ameliorates osteoporosis. This review of curcumenol provides a theoretical basis for further research and clinical applications. Full article
(This article belongs to the Special Issue Advances in Plant-Sourced Natural Compounds as Anticancer Agents)
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