The Inhibitory Effects of Ganoderma lucium on Cell Proliferation, Apoptosis, and TNF‐α‐Induced CCL2 Release in Genetically Different Triple‐Negative Breast Cancer Cells

Breast cancer is the second most lethal form of cancer among American women, presenting strong evidence of health disparities between Whites and African Americans. Triple-negative breast cancer (TNBC), in particular, is the most aggressive subtype, affecting African American women more aggressively. Several mushrooms have been shown to have nutritional value and contain bioactive compounds with a diversity of medicinal properties. The current study investigated the effects of Ganoderma lucidum, a mushroom that has been used across Asia as a nutraceutical and herbal remedy, on TNF-α stimulated MDA-MB-231 (White) and MDA-MB-468 (African American) TNBC cells. The extract's ability in causing cell toxicity, cell proliferation, and apoptosis was examined, and its modulatory effect on the mRNA expression of genes involved in cancer progression. The results showed that G. lucidum decreased cell viability in a dose-dependent manner in concentrations of 0.75 to 4.25 mg/mL, showing similar IC50s of 1.5 and 1.4 mg/mL MDA-MB-231 and MDA-MB-468 cells, respectively. After a 96-hr of treatment, the cell proliferation rate was reduced in both cell lines. However, the extract had a higher potency in MDA-MB-468, exhibiting more anti-proliferative effects in concentrations as low as 0.125 mg/mL. Apoptosis assays demonstrated that G. lucidum extract (2.75 mg/mL) increased the number of apoptotic cells in MDA MB-231, showing 90% of the apoptotic phase's analyzed, compared to 70% in MDA-MB-468 cells. Moreover, the mushroom extract downregulated mRNA expression of the proinflammatory cytokine, CCL2, reducing expression levels to less than 10%, compared to the cells treated with TNF-α only. This study demonstrates that the extract of G. lucidum may have an anti-cancer potential by inducing cytotoxicity, reducing cell proliferation, inducing apoptotic effects, and suppressing CCL2 expression in MDA-MB-231 and MDA-MB-468 TNBC cells. Furthermore, the results reveal that the genetically diverse TNBC cells used in this study responded differently to G. lucidum treatment. These results provide more evidence that genetically different cells may respond differently to treatments, explaining the inadequate therapeutic response in African American patients with advanced TNBC compared to other races.