Abstract
The anti-cancer activities of antibiotic anisomycin have been demonstrated in kidney, colon and ovarian cancers whereas its underlying mechanisms are not well elucidated. In this work, we investigated whether anisomycin is effective in sensitizes osteosarcoma cell response to chemotherapy. We show that anisomycin inhibits proliferation via inducing osteosarcoma cell arrest at G2/M phase, accompanied by the increased levels of mitotic marker cyclin B and the decreased levels of Rb and E2F-1. Anisomycin also induces apoptosis in a caspase-dependent manner in osteosarcoma cells. Importantly, anisomycin is less effective in normal control NIH3T3 cells compared to osteosarcoma cells. In addition, anisomycin inhibits osteosarcoma growth in xenograft mouse model and enhances the inhibitory effects of doxorubicin in osteosarcoma in vitro and in vivo. Mechanistically, anisomycin targets mitochondrial biogenesis in osteosarcoma as shown by the decreased mitochondrial membrane potential, suppressed mitochondrial respiration via decreasing complex I activity, reduced ATP production. Furthermore, mitochondrial biogenesis stimulator acetyl-L-Carnitine (ALCAR) significantly rescues the inhibitory effects of anisomycin in osteosarcoma cells. Our work demonstrates that anisomycin is active against osteosarcoma cells and the molecular mechanism of its action is the inhibition of mitochondrial biogenesis.
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This work was supported by a research grant provided by Xiangyang Central Hospital (201416081869).
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Chuanhua Cao and Haiying Yu are equal contributors and co-first authors.
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Cao, C., Yu, H., Wu, F. et al. Antibiotic anisomycin induces cell cycle arrest and apoptosis through inhibiting mitochondrial biogenesis in osteosarcoma. J Bioenerg Biomembr 49, 437–443 (2017). https://doi.org/10.1007/s10863-017-9734-8
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DOI: https://doi.org/10.1007/s10863-017-9734-8