HSP70 desensitizes osteosarcoma cells to baicalein and protects cells from undergoing apoptosis

Abstract

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.

Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy

“…This increased expression of HSP70 is potentially problematic, in that the protein is known to directly suppress the apoptotic cascade and protect cells from doxorubicin-mediated apoptosis in a variety of model systems (Gabai et al 1997(Gabai et al , 1995Karlseder et al 1996;Samali and Cotter 1996). Although we did not confirm a cytoprotective role for the increased HSP70 observed in canine OSA cell lines, induced overexpression of HSP70 in human OSA cell lines partially prevented apoptosis induced by the flavenoid baicalein (Ding et al 2014).…”

The Fascinating Effects of Baicalein on Cancer: A Review

“…HSP70, which is essential for the survival and partial protection of tumor cells from apoptosis, was upregulated after baicalein treatment. This finding suggested that the anti-osteosarcoma property of baicalein can be strengthened in combination with some inhibitors of HSP70 [73]. Broadly speaking, baicalein could be a potential future treatment of patients with osteosarcoma.…”

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

“…Baicalein is a new drug, and baicalein-induced apoptosis in osteosarcoma cells was via a mitochondrial pathway that involved both caspase-dependent and -independent mechanisms. However, baicalein treatment notably upregulated the expression of HSP70, which partially prevented human osteosarcoma cells from undergoing apoptosis, and decreased the sensitivity of osteosarcoma cells to baicalein via the activation of the PI3K/AKT and MAPK/ERK pathways [66]. Celecoxib, a cyclooxygenase-2 inhibitor, induced apoptosis in human osteosarcoma cell line MG-63 via the downregulation of PI3K/Akt, and decreased the level of survival and bcl-2 in cells treated with the combination of celecoxib and cisplatin or wortmannin, a specific PI3K inhibitor [67].…”