This study aimed to investigate the cytotoxic and apoptotic effects of Ganoderma lucidum, Pleurotus ostreatus, Pleurotus eryngii, and Inonotus hispidus fungal extracts on HT-29 and HCT-116 colorectal cancer cell lines and to search the DNA damage and oxidative stress caused by these extracts. Accordingly, mushroom extracts were applied to colorectal cancer cell lines in vitro, and the IC50 result was obtained with the MTT test. According to the IC50 result, Ganoderma lucidum extract had the most effective cytotoxicity value among all used mushroom extracts. TAS, TOS, and NRF-2 tests were used to investigate the molecular effect of Ganoderma lucidum extract on oxidative stress; the DNA ladder test was performed to assess DNA damage, the Scratch assay method was applied for cell migration analysis, and the colony assay was used to determine the colony formation potential of the cells. The results showed that Ganoderma lucidum mushroom extract reduces cell proliferation, colony formation, and NRF-2, induces DNA damage, slows cell migration, and increases oxidative stress. This study shows that Ganoderma lucidum mushroom extract reduces cell proliferation through damaging cellular DNA and has a cytotoxic effect in colorectal cancer cell lines.
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