Phallus indusiatus Extracts Promoted MCF-7 Apoptosis Under TNFα-induced Tumor Microenvironment by Attenuating NF-kappaB and Akt Activation.

OBJECTIVE: To evaluate the anti-inflammatory and anticancer effects of Phallus indusiatus extracts, particularly in modulating inflammatory microenvironments and sensitizing lapatinib-induced cytotoxicity in breast cancer cells. METHODS: Phallus indusiatus (bamboo mushroom) extracts were prepared using water extraction from fresh and dried specimens. The anti-inflammatory effects were assessed using RAW246.7 cells by measuring NO production, while cytotoxicity and proliferation effects were evaluated in MCF-7 and MCF-10A breast cell lines. To mimic the inflammatory microenvironment of breast cancer, MCF-7 cells were treated with TNFα to induce lapatinib resistance. The effects of the extracts on cell viability, apoptosis, and NF-kappaB signaling were evaluated under inflammatory microenvironment-mimicking conditions. Co-treatment with lapatinib and the extracts was analyzed for synergistic cytotoxic effects and pathway modulation. RESULTS: P. indusiatus extracts demonstrated anti-inflammatory effects by reducing NO production in RAW246.7 cells. The extracts showed no cytotoxicity on MCF-7 and MCF-10A cells, with an observed proliferation increase in MCF-10A but not MCF-7. Under inflammatory microenvironment-mimicking conditions induced by TNFα, the extracts slightly reduced MCF-7 cell viability in a dose-dependent manner. Additionally, the extracts sensitized lapatinib-induced cytotoxicity by increasing apoptotic cell populations. Mechanistically, co-treatment with the extracts attenuated AKT and NF-kappaB activation in a dose-dependent manner. CONCLUSION: These findings highlight the potential of P. indusiatus extracts as supplementary food for breast cancer patients, particularly in inflammatory microenvironment conditions.