HSP70 desensitizes osteosarcoma cells to baicalein and protects cells from undergoing apoptosis.
Baicalein is a new drug that has shown promising anti-cancer effects against a broad spectrum of tumors. However, the potential effect on osteosarcoma cells and the mechanisms involved are still largely unknown. Resistance to chemotherapy remains a major obstacle in cancer therapy. Therefore, the aim of the present study was to investigate the anti-tumor effect of baicalein on human osteosarcoma cancer cells and the molecular mechanism involved, as well as identify possible mechanisms of drug resistance. Our results revealed that baicalein-induced apoptosis in osteosarcoma cells was via a mitochondrial pathway involving both caspase-dependent and independent mechanisms. Notably, baicalein treatment upregulated the expression of HSP70, which partially prevented human osteosarcoma cells from undergoing apoptosis. Moreover, it was revealed that HSP70 expression decreased the sensitivity of osteosarcoma cells to baicalein via activation of PI3K/AKT and MAPK/ERK pathways. These results suggest that targeting HSP70-mediated drug resistance, in combination with chemotherapy drugs, may provide novel therapeutic opportunities.
Department of Orthopedics, The Third Affiliated Hospital of Suzhou University, No 185 Juqian Street, Changzhou, 213003, China.
Lianghua
L
Ding
Shuanghua
S
He
Xiaoliang
X
Sun
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D044950:Flavanones / Q000378:metabolism* / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D044950:Flavanones; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; C006680:baicalein; D020169:Caspases