Ganoderma lucidum alcohol extract targets mutant p53 signaling to inhibit proliferation in triple-negative breast brain metastasis cancer.

Abstract

Triple-negative breast cancer (TNBC) is among the most aggressive subtypes of breast cancer, frequently characterized by invasive growth, metastasis, and poor clinical outcomes. Brain metastasis, commonly observed in TNBC patients, significantly worsens prognosis and survival rates. Current therapeutic strategies for TNBC brain metastases remain limited and largely ineffective. Mutant p53, common in TNBC, promotes malignancy and metastasis. MDA-MB-231 cells and their brain metastatic variant (MDA-MB-231-Br) harbor a p53 R280K mutation. Ganoderma lucidum, historically known for anticancer properties, has unclear effects on breast cancer brain metastasis. This study evaluated the impact of alcohol-extracted Ganoderma lucidum on TNBC brain metastasis cells via mutant p53 inhibition. Treatment with 10% G. lucidum alcohol extract for 48 hours significantly reduced proliferation in MDA-MB-231 and MDA-MB-231-Br cells. Knockdown of p53 confirmed its role in cell proliferation. Additionally, MG132, proteasome inhibitor, restored p53 levels, indicating G. lucidum extract promotes p53 degradation. Collectively, our findings suggest that alcohol-extracted G. lucidum inhibits the proliferation of TNBC brain metastatic cells by promoting the degradation of mutant p53. This mechanistic insight provides a potential therapeutic strategy for mitigating brain metastasis in triple-negative breast cancer.