Abstract:
: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.
journal_name
Oncol Lettjournal_title
Oncology lettersauthors
Yang Y,Zhou H,Liu W,Wu J,Yue X,Wang J,Quan L,Liu H,Guo L,Wang Z,Lian X,Zhang Qdoi
10.3892/ol.2018.9475subject
Has Abstractpub_date
2018-11-01 00:00:00pages
6515-6521issue
5eissn
1792-1074issn
1792-1082pii
OL-0-0-9475journal_volume
16pub_type
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