Breast cancer is a common malignant
tumor among females, with
triple-negative breast cancer being an important type accounting for 15-20% of all
breast cancer cases.
Triple-negative breast cancer is one of the most aggressive types of
cancer without standard
adjuvant chemotherapy.
Ganoderic acid A (GA-A) is one of the major bioactive Ganoderma
triterpenoids isolated from Ganoderma, which are recognized for their preventative and
therapeutic effects. In the present study, the
antineoplastic effect of GA-A on human
breast cancer was investigated and the pro-apoptotic function of
Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3 on the function of GA-A was revealed. GA-A treatment inhibited the invasion of MDA-MB-231 cells. In addition, GA-A exhibited significant antitumor activity by enhancing the apoptotic index and
reactive oxygen species production. In the present study, GA-A was identified to directly inhibit JAK2 phosphorylation and STAT3 downstream activation. In addition, GA-A suppressed STAT3 target gene expression, including
B cell lymphoma-extra-large and Myeloid cell
leukemia 1, resulting in elevated levels of
proteins associated with mitochondrial apoptosis in addition to inhibitors of
cyclin-dependent kinase. GA-A, in combination with
AG490, a JAK2/STAT3 inhibitor, further decreased MDA-MB-231 cell viability. In conclusion, GA-A treatment inhibited
breast cancer cell viability via JAK2/STAT3 downregulation and may regulate associated targets to serve an anti-MDA-MB-231 role, including mitochondrial apoptosis and regulating the expression of cell-cycle-associated factors.