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Anti-tumor Effects of Natural Products
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Anti-tumor Effects of Natural Products

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

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 22461

Special Issue Editors

Prof. Dr. Quan Zhang

E-Mail Website
Guest Editor
College of Pharmacy, Nankai University, Tianjin, China
Interests: natural product; anticaner; ferroptosis; medicinal chemistry; total synthesis; drug chemical biology; new drug R&D
Dr. Yahui Ding

E-Mail Website
Guest Editor
College of Chemistry, Nankai University, Tianjin, China
Interests: chemical biology; target exploration; mechanism study

Special Issue Information

Dear Colleagues,

Cancer continues to be a major public health challenge worldwide. Despite many progresses have already been made in current therapeutic treatments against cancer, new approaches are still required to improve the efficacy of present methods. Both synthetic drugs and natural extracted compounds have already proved that natural product is a promising solution in fight against aggressive tumors. As one of the most consistently successful sources of drug leads, natural products have made massive progresses in developing innovate anticancer medicine. Herein, we launch this special issue to provide a platform to share the recent efforts in natural product chemistry, medicinal chemistry, pharmacology and chemical biology towards innovative strategies against tumor, to collect the most innovative discovery of natural antitumor agents and to share a better view in this area. Researchers who involved in anti-tumor natural-products-based drug discovery are invited to contribute original papers or reviews to this special issue.

Prof. Dr. Quan Zhang
Dr. Yahui Ding
Guest Editors

Manuscript Submission Information

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Keywords

  • natural products
  • anticancer
  • antitumor
  • antiproliferative
  • plant extracts
  • structure modification
  • total synthesis
  • appotosis
  • programmed cell death

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Published Papers (6 papers)

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Research

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22 pages, 5259 KiB  
Article
Strophanthidin Induces Apoptosis of Human Lung Adenocarcinoma Cells by Promoting TRAIL-DR5 Signaling
by Xiao Tian, Liangzhen Gu, Fangang Zeng, Xingkai Liu, Yang Zhou, Yang Dou, Juanjuan Han, Yao Zhao, Yanyan Zhang, Qun Luo and Fuyi Wang
Molecules 2024, 29(4), 877; https://doi.org/10.3390/molecules29040877 - 16 Feb 2024
Cited by 6 | Viewed by 1947
Abstract
Strophanthidin (SPTD), one of the cardiac glycosides, is refined from traditional Chinese medicines such as Semen Lepidii and Antiaris toxicaria, and was initially used for the treatment of heart failure disease in clinic. Recently, SPTD has been shown to be a potential [...] Read more.
Strophanthidin (SPTD), one of the cardiac glycosides, is refined from traditional Chinese medicines such as Semen Lepidii and Antiaris toxicaria, and was initially used for the treatment of heart failure disease in clinic. Recently, SPTD has been shown to be a potential anticancer agent, but the underlying mechanism of action is poorly understood. Herein, we explored the molecular mechanism by which SPTD exerts anticancer effects in A549 human lung adenocarcinoma cells by means of mass spectrometry-based quantitative proteomics in combination with bioinformatics analysis. We revealed that SPTD promoted the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2, or DR5) in A549 cells to activate caspase 3/6/8, in particular caspase 3. Consequently, the activated caspases elevated the expression level of apoptotic chromatin condensation inducer in the nucleus (ACIN1) and prelamin-A/C (LMNA), ultimately inducing apoptosis via cooperation with the SPTD-induced overexpressed barrier-to-autointegration factor 1 (Banf1). Moreover, the SPTD-induced DEPs interacted with each other to downregulate the p38 MAPK/ERK signaling, contributing to the SPTD inhibition of the growth of A549 cells. Additionally, the downregulation of collagen COL1A5 by SPTD was another anticancer benefit of SPTD through the modulation of the cell microenvironment. Full article
(This article belongs to the Special Issue Anti-tumor Effects of Natural Products)
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15 pages, 5739 KiB  
Article
Gastrodin Induces Ferroptosis of Glioma Cells via Upregulation of Homeobox D10
by Wenpeng Cao, Jinzhi Lan, Zhirui Zeng, Wenfeng Yu and Shan Lei
Molecules 2023, 28(24), 8062; https://doi.org/10.3390/molecules28248062 - 13 Dec 2023
Cited by 7 | Viewed by 1900
Abstract
Gastrodin, the primary bioactive compound found in Gastrodia elata, has been shown to exhibit neuroprotective properties in a range of neurological disorders. However, the precise mechanisms through which gastrodin influences glioma cells remain unclear, and there is a scarcity of data regarding its [...] Read more.
Gastrodin, the primary bioactive compound found in Gastrodia elata, has been shown to exhibit neuroprotective properties in a range of neurological disorders. However, the precise mechanisms through which gastrodin influences glioma cells remain unclear, and there is a scarcity of data regarding its specific effects. To ascertain the viability of glioma cell lines LN229, U251, and T98, the CCK-8 assay, a colony formation assay, and a 3D culture model were employed, utilizing varying concentrations of gastrodin (0, 5, 10, and 20 μM). Gastrodin exhibited a notable inhibitory effect on the growth of glioma cells, as evidenced by its ability to suppress colony formation and spheroid formation. Additionally, gastrodin induced ferroptosis in glioma cells, as it can increase the levels of reactive oxygen species (ROS) and peroxidized lipids, and reduced the levels of glutathione. Using a subcutaneous tumor model, gastrodin was found to significantly inhibit the growth of the T98 glioma cell line in vivo. Using high-throughput sequencing, PPI analysis, and RT-qPCR, we successfully identified Homeobox D10 (HOXD10) as the principal target of gastrodin. Gastrodin administration significantly enhanced the expression of HOXD10 in glioma cells. Furthermore, treatment with gastrodin facilitated the transcription of ACSL4 via HOXD10. Notably, the inhibition of HOXD10 expression impeded ferroptosis in the cells, which was subsequently restored upon rescue with gastrodin treatment. Overall, our findings suggest that gastrodin acts as an anti-cancer agent by inducing ferroptosis and inhibiting cell proliferation in HOXD10/ACSL4-dependent pathways. As a prospective treatment for gliomas, gastrodin will hopefully be effective. Full article
(This article belongs to the Special Issue Anti-tumor Effects of Natural Products)
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12 pages, 2564 KiB  
Article
Coumarins from Jinhua Finger Citron: Separation by Liquid–Liquid Chromatography and Potential Antitumor Activity
by Chaoyue Wang, Jiangang Huang, Zhiling Zhou, Ping Xu, Jingyi Shi, Yushun Yang, Shengqiang Tong and Hongyu Hu
Molecules 2023, 28(19), 6917; https://doi.org/10.3390/molecules28196917 - 3 Oct 2023
Cited by 4 | Viewed by 1764
Abstract
In this paper, liquid–liquid chromatography was introduced for the first time for the separation of fingered citron (Citrus medica L. var. sarcodactylis Swingle). The fingered citron cultivated in Jinhua is of significant industrial and medicinal value, with several major coumarin compounds detected [...] Read more.
In this paper, liquid–liquid chromatography was introduced for the first time for the separation of fingered citron (Citrus medica L. var. sarcodactylis Swingle). The fingered citron cultivated in Jinhua is of significant industrial and medicinal value, with several major coumarin compounds detected in its extract. Therefore, further separation for higher purity was of necessity. A preparative liquid–liquid chromatographic method was developed by combining two elution modes (isocratic and step-gradient) with selection according to different polarities of the target sample. Five coumarin derivatives—5,7-dimethoxycoumarin (52.6 mg, 99.6%), phellopterin (4.9 mg, 97.1%), 5-prenyloxy-7-methoxycoumarin (6.7 mg, 98.7%), 6-hydroxy-7-methoxycoumarin (7.1 mg, 82.2%), and byakangelicol (10.5 mg, 90.1%)—with similar structures and properties were isolated on a large scale from 100 mg of petroleum ether (PE) extract and 100 mg of ethyl acetate (EA) extract in Jinhua fingered citron. The productivity was much improved. The anti-growth activity of the isolated coumarins was evaluated against three cancer cell lines (HeLa, A549, and MCF7) with an MTT assay. The coumarins demonstrated potential anti-tumor activity on the HeLa cell line, with 5,7-dimethoxycoumarin in particular exhibiting the best anti-growth activity (IC50 = 10.57 ± 0.24 μM) by inhibiting proliferation. It inhibited colony formation and reduced the size of the tumor sphere in a concentration-dependent manner. The main mechanism was confirmed as inducing apoptosis. This work was informative for further studies aimed at exploring new natural-product-based antitumor agents. Full article
(This article belongs to the Special Issue Anti-tumor Effects of Natural Products)
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14 pages, 11118 KiB  
Article
Terpinen-4-ol Induces Ferroptosis of Glioma Cells via Downregulating JUN Proto-Oncogene
by Wenpeng Cao, Yumei Li, Zhirui Zeng and Shan Lei
Molecules 2023, 28(12), 4643; https://doi.org/10.3390/molecules28124643 - 8 Jun 2023
Cited by 11 | Viewed by 2367
Abstract
According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or [...] Read more.
According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or not glioma cell lines U251, U87, and LN229 are viable, CCK8 was used as an assay and a colony formation assay was performed using different concentrations of T4O (0, 1, 2, and 4 μM). The effect of T4O on the proliferation of glioma cell line U251 was detected through the subcutaneous implantation of the tumor model. Through high-throughput sequencing, a bioinformatic analysis, and real-time quantitative polymerase chain reactions, we identified the key signaling pathways and targets of T4O. Finally, for the measurement of the cellular ferroptosis levels, we examined the relationship between T4O, ferroptosis, and JUN and the malignant biological properties of glioma cells. T4O significantly inhibited glioma cell growth and colony formation and induced ferroptosis in the glioma cells. T4O inhibited the subcutaneous tumor proliferation of the glioma cells in vivo. T4O suppressed JUN transcription and significantly reduced its expression in the glioma cells. The T4O treatment inhibited GPX4 transcription through JUN. The overexpression of JUN suppressed ferroptosis in the cells rescued through T4O treatment. Taken together, our data suggest that the natural product T4O exerts its anti-cancer effects by inducing JUN/GPX4-dependent ferroptosis and inhibiting cell proliferation, and T4O will hope-fully serve as a prospective compound for glioma treatment. Full article
(This article belongs to the Special Issue Anti-tumor Effects of Natural Products)
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Review

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44 pages, 4800 KiB  
Review
Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications
by Mateusz Kciuk, Manzar Alam, Nemat Ali, Summya Rashid, Pola Głowacka, Rajamanikandan Sundaraj, Ismail Celik, Esam Bashir Yahya, Amit Dubey, Enfale Zerroug and Renata Kontek
Molecules 2023, 28(13), 5246; https://doi.org/10.3390/molecules28135246 - 6 Jul 2023
Cited by 37 | Viewed by 6799
Abstract
Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. [...] Read more.
Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis. Full article
(This article belongs to the Special Issue Anti-tumor Effects of Natural Products)
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15 pages, 334 KiB  
Review
Bovine Colostrum Treatment of Specific Cancer Types: Current Evidence and Future Opportunities
by Ahmad R. Alsayed, Luai Z. Hasoun, Heba A. Khader, Iman A. Basheti and Andi Dian Permana
Molecules 2022, 27(24), 8641; https://doi.org/10.3390/molecules27248641 - 7 Dec 2022
Cited by 8 | Viewed by 7089
Abstract
Worldwide, the incidence of cancer is on the rise. Current cancer treatments include chemotherapy, radiation therapy, and surgery. Chemotherapy and radiation treatment are typically associated with severe adverse effects and a decline in patients’ quality of life. Anti-cancer substances derived from plants and [...] Read more.
Worldwide, the incidence of cancer is on the rise. Current cancer treatments include chemotherapy, radiation therapy, and surgery. Chemotherapy and radiation treatment are typically associated with severe adverse effects and a decline in patients’ quality of life. Anti-cancer substances derived from plants and animals need to be evaluated therapeutically as it is cost-effective, have fewer side effects, and can improve cancer patients’ quality of life. Recently, bovine colostrum (BC) has attracted the interest of numerous researchers investigating its anti-cancer potential in humans. Dressings loaded with BC are beneficial in treating chronic wounds and diabetic foot ulcers. Lactoferrin, a glycoprotein with potent anti-oxidant, anti-inflammatory, anti-cancer, and anti-microbial effects, is abundant in BC. The BC pills successfully promote the regression of low-grade cervical intraepithelial neoplasia when administered intravaginally. The biological, genetic, and molecular mechanisms driving BC remain to be determined. Oral BC supplements are generally well-tolerated, but some flatulence and nausea may happen. To evaluate the therapeutic effects, long-term safety, and appropriate dosages of BC drugs, well-designed clinical trials are necessary. The purpose of this article is to emphasize the anti-cancer potential of BC and its constituents. Full article
(This article belongs to the Special Issue Anti-tumor Effects of Natural Products)
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