Monday Article #40: The cytotoxic effects of Cordyceps militaris on cancer cell lines
Cancer is the world's leading cause of death, accounting for nearly 10 million deaths in 2020 (World Health Organization, 2022). Breast, lung, colon, rectum, and prostate cancers are the most common types (World Health Organization, 2022). Cancer is a broad term that refers to a wide range of diseases that can affect any part of the body. Malignant tumours and neoplasms are other terms used. One distinguishing feature of cancer is the rapid formation of abnormal cells that grow beyond their normal boundaries and can then invade neighbouring parts of the body and spread to other organs; this process is known as metastasis. The primary cause of cancer death is widespread metastasis (World Health Organization, 2022).
Treatment options vary depending on the stage of cancer progression and include surgery, radiotherapy, chemotherapy, and biological therapy. Current anti-cancer chemotherapeutic agents are formulated with toxic solvents, posing a number of side effects and complications in the clinical management of various types of cancer. When administered, these drugs lack specificity and cause significant damage to noncancerous tissues. This frequently results in serious, unfavourable side effects such as neuro- and/or renal toxicity, bone marrow suppression, hair loss (alopecia), and sloughing of gut epithelial cells [1-3]. This demonstrates the critical need for novel, effective, and less-toxic therapeutic agents. As a result, the search for new, natural anticancer bioactive compounds has become a massive undertaking (Md et al., 2018).
Figure 1: An illustration of Cordyceps militaris Mushroom (Shields, n.d.)
Cordyceps militaris (C. militaris) is a fungus with a long history of use in folk medicine, and its biological and medicinal functions have been extensively researched (Lee et al., 2020). The anticancer properties of this mushroom can be accessed from the hot water, chloroform, ethyl acetate, and ethanol extracts from fruit bodies and mycelial biomass against human pancreatic, colon, prostate, and breast cancer cells. Cell viability detection is critical in many biological fields, particularly toxicology and pharmacology for assessing toxic effects elicited by chemicals, drugs, or contaminated environmental samples, respectively. As a result, the XTT cell proliferation assay, a quantitative colorimetric method, was used to assess the cytotoxicity of tested mushroom extracts on cancer cell lines. Cordyceps mycelium and fruiting body extracts have been shown in the literature to have direct cytotoxic activity against a variety of cancer cells, including lung carcinoma, B16 melanoma, lymphocytic, prostate (PC3), breast (MCF7), hepatocellular (HepG2, Hep3B), and colorectal (HT-29 and HCT116) cells [21,22].
Figure 2: An illustration indicating two major parts of a mushroom (Host Defense, 2021)
The XTT assay was used to determine the effect of C. militaris Mycelial Biomass (MB) extract on the viability of HPAF, HCT116, PC3, and T47D cells. It is worth noting that, of all the extracts tested, those from C. militaris had the most profound effect on cell viability. The treatment of HCT116 and T47D cell lines with ethanol and ethyl acetate extracts for 24 hours, 48 hours, and 72 hours produced the most promising results (Figure 1). All extract treatments at high concentrations (250-500 g/ml) inhibited PC3 cell viability, with a decrease of 60-70% after 24 hours and 90-95% after 48h and 72h of incubation. After 48 and 72 hours, all extracts at the same dose showed a 70-80% decrease in HPAF cell viability. Furthermore, inhibition of cancer cell viability was discovered to be dose-dependent.
Figure 3: The effect of different C. militaris MB extracts on the viability of HPAF, HCT116, PC3, and T47D cells by XTT assay (Md et al., 2018)
Of all extracts examined for their effect on cell viability, the Fruiting Body (FB) ethyl acetate extract that showed the most promising results was chosen for further evaluation. The strongest effect was seen after treating the HPAF-II, HCT116, and PC3 cell lines with 500g/ml C. militaris FB extract, which inhibited cell growth by more than 80%. (Figure 3). A dose of 250 µg/ml also induced more than 50% inhibition in cell growth for all cell lines treated with C. militaris FB extract.
Figure 4: The effect of the selected extracts on the viability of different cancer cell lines by XTT assay. Statistical significance was determined by one way ANOVA, P<0.001. (Md et al., 2018)
In another study conducted, Cordyceps militaris grown on germinated soybean was able to induced apoptosis on KRAS-drived Colorectal cancer cells. The results (Figure …) also proves once again that the inhibition of cancer cell viability by Cordyceps militaris is dose-dependent.
Figure 5: Graphical abstract of the effects of GSC (Cordyceps militaris grown on germinated soybean) on cancer cells (Seo et al., 2019)
In conclusion, Cordyceps militaris indeed contains various medicinal properties which can be utilized as an alternative for the treatment of cancer. It can be surprising how a naturally occurring fungus possesses more specificity than a lot of the readily available cancer treatments now. With that, it gives us a hope that cancer can become a curable condition one day in the future. However, a lot more research needs to be carried out to ensure that this alternative is indeed safe for humans and will not possess any harm in the long run.
Host Defense (2021). Why All Host Defense Supplements Are Powered by Mushroom Mycelium. Retrieved from https://hostdefense.com/blogs/host-defense-blog/mycelium-explained.
Md, A., Gs, B., Jsl, C. and Sp, W. (2018). ‘Cytotoxic Activity of Medicinal Mushroom Extracts on Human Cancer Cells’, SF Journal of Biotechnology and Biomedical Engineering, 1(1) [online] Available at: https://scienceforecastoa.com/Articles/SJBBE-V1-E1-1006.pdf. (Accessed: 21 December 2022)
Lee, C.-T., Huang, K.-S., Shaw, J.-F., Chen, J.-R., Kuo, W.-S., Shen, G., Grumezescu, A.M., Holban, A.M., Wang, Y.-T., Wang, J.-S., Hsiang, Y.-P., Lin, Y.-M., Hsu, H.-H. and Yang, C.-H. (2020). ‘Trends in the Immunomodulatory Effects of Cordyceps militaris: Total Extracts, Polysaccharides and Cordycepin.’, Frontiers in Pharmacology, 11. [Online] DOI:10.3389/fphar.2020.575704. (Accessed: 21 December 2022)
Seo, H., Song, J., Kim, M., Han, D.-W., Park, H.-J. and Song, M. (2019). ‘Cordyceps militaris Grown on Germinated Soybean Suppresses KRAS-Driven Colorectal Cancer by Inhibiting the RAS/ERK Pathway’, Nutrients, 11(1), p.20. [Online] DOI: 10.3390/nu11010020. (Accessed: 21 December 2022)
Shields, T.. (n.d.). A Friendly Guide To Cordyceps Mushrooms. Retrieved from https://learn.freshcap.com/tips/cordyceps-mushroom-health/.
World Health Organization (2022). Cancer. Retrived from https://www.who.int/news-room/fact-sheets/detail/cancer.
This article was written by Thiiben A/L Krishnan Sami