Abstract
Cordyceps militaris is a well-known medicinal mushroom. It is non-toxic and has clinical health benefits including cancer inhibition. However, the anticancer effects of C. militaris cultured in brown rice on breast cancer have not yet been reported. In this study, we simultaneously investigated the anticancer effects of cordycepin and an extract of C. militaris cultured in brown rice on MCF-7 human breast cancer cells using a cell viability assay, cell staining with Hoechst 33342, and an image-based cytometric assay. The C. militaris concentrate exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 73.48 µg/mL. Cordycepin also exhibited significant MCF-7 cell inhibitory effects, and its IC50 value was 9.58 µM. We applied network pharmacological analysis to predict potential targets and pathways of cordycepin. The gene set enrichment analysis showed that the targets of cordycepin are mainly associated with the hedgehog signaling, apoptosis, p53 signaling, and estrogen signaling pathways. We further verified the predicted targets related to the apoptosis pathway using western blot analysis. The C. militaris concentrate and cordycepin exhibited the ability to induce apoptotic cell death by increasing the cleavage of caspase-7 -8, and -9, increasing the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) protein expression ratio, and decreasing the protein expression of X-linked inhibitor of apoptosis protein (XIAP) in MCF-7 cells. Consequently, the C. militaris concentrate and cordycepin exhibited significant anticancer effects through their ability to induce apoptosis in breast cancer cells.
Highlights
The death rate due to breast cancer is 14%, and this malignancy accounts for 23% of all cancer cases
Cell viability assays were performed to evaluate the cytotoxic effects of the C. militaris concentrate and cordycepin on MCF-7 cells
The C. militaris concentrate cultured in brown rice and cordycepin isolated from
Summary
The death rate due to breast cancer is 14%, and this malignancy accounts for 23% of all cancer cases. Researchers in the past have urged continuing research on potential and effective natural products so as to identify their bioactive compounds for the treatment of breast cancer Medicinal mushrooms such as Cordyceps species, Agaricus bisporus, Pleurotus eous, Ganoderma lucidum, and Amauroderma rude have shown anticancer effects on breast cancer both in vivo and in vitro [7,12]. Cordyceps militaris, which is known as a representative Cordyceps species, has been cultured in brown rice, and its extract has been reported to have anticancer effects, including effects against breast cancer [25]. We verified the predicted targets of cordycepin related to the apoptosis pathway in vitro
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