Targeting Drug Chemo-Resistance in Cancer Using Natural Products

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Oct 23

PMID 34680470

Citations 43

Authors

Wamidh H Talib

Ahmad Riyad Alsayed

Muna Barakat

May Ibrahim Abu-Taha

Asma Ismail Mahmod

Affiliations

Soon will be listed here.

Abstract

Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

Citing Articles

Antiproliferative Activity and Apoptotic Mechanisms of β-Sitosterol and Its Derivatives as Anti-Breast Cancer Agents: In Silico and In Vitro.

Mutakin M, Pangestu L, Hidayat N, Abdullah F, Hadisaputri Y J Exp Pharmacol. 2025; 17:107-121.

PMID: 39989471 PMC: 11844196. DOI: 10.2147/JEP.S496986.

Quinalizarin induces autophagy, apoptosis and mitotic catastrophe in cervical and prostate cancer cells.

Trybus W, Trybus E, Obarzanowski M, Krol T Sci Rep. 2025; 15(1):5252.

PMID: 39939343 PMC: 11822151. DOI: 10.1038/s41598-025-89847-8.

Mechanistic Insights into Silymarin-Induced Apoptosis and Growth Inhibition in SPC212 Human Mesothelioma Cells.

Tomsuk O, Kacar S Cell Biochem Biophys. 2025; .

PMID: 39747779 DOI: 10.1007/s12013-024-01650-w.

Herbal drug‑based nanotherapy for hepatocellular carcinoma: Quercetin‑contained nanocarrier as a multipurpose therapeutic agent against hepatocellular carcinoma (Review).

Batsukh T, Tsend-Ayush A Biomed Rep. 2024; 22(2):29.

PMID: 39720296 PMC: 11668132. DOI: 10.3892/br.2024.1907.

2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione mediates the effect of ROS-enhanced PI3K/Akt/mTOR pathway on autophagy in breast cancer.

Chen L, Chen M, Xie Y, Zhang Y, Mo S, He Y FEBS Open Bio. 2024; 15(3):474-489.

PMID: 39648951 PMC: 11891764. DOI: 10.1002/2211-5463.13940.

References

Tinoush B, Shirdel I, Wink M . Phytochemicals: Potential Lead Molecules for MDR Reversal. Front Pharmacol. 2020; 11:832. PMC: 7317022. DOI: 10.3389/fphar.2020.00832. View

Srivastava R, Li C, Khan J, Banerjee N, Chow L, Athar M . Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells. Proc Natl Acad Sci U S A. 2019; 116(49):24583-24592. PMC: 6900636. DOI: 10.1073/pnas.1911393116. View

Efferth T . From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017; 46:65-83. DOI: 10.1016/j.semcancer.2017.02.009. View

Young A, Chan E, Hu X, Kochl R, Crawshaw S, High S . Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006; 119(Pt 18):3888-900. DOI: 10.1242/jcs.03172. View

Weinlich R, Oberst A, Beere H, Green D . Necroptosis in development, inflammation and disease. Nat Rev Mol Cell Biol. 2016; 18(2):127-136. DOI: 10.1038/nrm.2016.149. View

Kueck A, Opipari Jr A, Griffith K, Tan L, Choi M, Huang J . Resveratrol inhibits glucose metabolism in human ovarian cancer cells. Gynecol Oncol. 2007; 107(3):450-7. DOI: 10.1016/j.ygyno.2007.07.065. View

Fan S, Li L, Chen S, Yu Y, Qi M, Tashiro S . Silibinin induced-autophagic and apoptotic death is associated with an increase in reactive oxygen and nitrogen species in HeLa cells. Free Radic Res. 2011; 45(11-12):1307-24. DOI: 10.3109/10715762.2011.618186. View

Lee K, Lo H, Tang W, Hsiao H, Yang P . A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine. Sci Rep. 2014; 4:6394. PMC: 5377252. DOI: 10.1038/srep06394. View

Viale A, Pettazzoni P, Lyssiotis C, Ying H, Sanchez N, Marchesini M . Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014; 514(7524):628-32. PMC: 4376130. DOI: 10.1038/nature13611. View

10.

Dupont C, Armant D, Brenner C . Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med. 2009; 27(5):351-7. PMC: 2791696. DOI: 10.1055/s-0029-1237423. View

11.

Pacholak L, Amarante M, Guembarovski R, Watanabe M, Panis C . Polymorphisms in GSTT1 and GSTM1 genes as possible risk factors for susceptibility to breast cancer development and their influence in chemotherapy response: a systematic review. Mol Biol Rep. 2020; 47(7):5495-5501. DOI: 10.1007/s11033-020-05555-8. View

12.

Cheng Y, Qiu F, Ye Y, Guo Z, Tashiro S, Onodera S . Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38-nuclear factor-kappa B survival pathways in oridonin-treated murine fibrosarcoma L929 cells. FEBS J. 2009; 276(5):1291-306. DOI: 10.1111/j.1742-4658.2008.06864.x. View

13.

Jatoi A, Ellison N, Burch P, Sloan J, Dakhil S, Novotny P . A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Cancer. 2003; 97(6):1442-6. DOI: 10.1002/cncr.11200. View

14.

Cushman M, Nagarathnam D . Cytotoxicities of some flavonoid analogues. J Nat Prod. 1991; 54(6):1656-60. DOI: 10.1021/np50078a027. View

15.

Sjostrom J, Blomqvist C, Von Boguslawski K, Bengtsson N, Mjaaland I, Malmstrom P . The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer. Clin Cancer Res. 2002; 8(3):811-6. View

16.

Jia L, Zhang R, Shen L, Yang A . Regulators of carcinogenesis: emerging roles beyond their primary functions. Cancer Lett. 2014; 357(1):75-82. DOI: 10.1016/j.canlet.2014.11.048. View

17.

Nair B, Anto R, M S, Nath L . Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An and Approach. Adv Pharm Bull. 2020; 10(3):472-476. PMC: 7335979. DOI: 10.34172/apb.2020.058. View

18.

Cartee L, Kucera G . Protein kinase C modulation and anticancer drug response. Cancer Invest. 2000; 18(8):731-9. DOI: 10.3109/07357900009012205. View

19.

Wang H, Wang X, Liu L, Qin G, Kang T . Tigliane diterpenoids from the Euphorbiaceae and Thymelaeaceae families. Chem Rev. 2015; 115(9):2975-3011. DOI: 10.1021/cr200397n. View

20.

Dennis T, Fanous M, Mousa S . Natural products for chemopreventive and adjunctive therapy in oncologic disease. Nutr Cancer. 2009; 61(5):587-97. DOI: 10.1080/01635580902825530. View