Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells. In this study, confocal fluorescence microscopy experiments revealed that TERT translocates from the nucleus to mitochondria in cisplatin treated osteosarcoma cells. We observed decreased apoptosis rate and improved mitochondrial function in TERT-overexpressing cells following cisplatin treatment. Based on these results, we further established that TERT inhibits cisplatin-induced apoptosis independently of telomerase reverse transcriptase activity. Moreover, TERT suppressed cisplatin-induced apoptosis and improved mitochondrial function via alleviating intracellular ROS in osteosarcoma cells. Our finding that TERT shuttles from the nucleus to the mitochondrion in response to cisplatin treatment and inhibits cisplatin-induced apoptosis in osteosarcoma cells may be especially important to overcome drug resistance.
Osteosarcoma is a very common type of malignant bone tumor in children and young adults and aberrant activation of Wnt/β-catenin signaling pathway has been discovered in osteosarcoma. The traditional Chinese medicine baicalein was proved to have anti-proliferative and anti-metastatic properties in osteosarcoma, but the mechanism remained poorly understood. In the present study, we assessed the effects of baicalein on osteosarcoma and detected the potential molecular mechanism. We found that baicalein significantly suppressed the proliferation of osteosarcoma cells in a concentration- and time-dependent manner. In additional, baicalein could induce apoptosis and cell cycle arrest and reduce cell motility. Moreover, the level of β-catenin and its target genes, including c-myc, cyclinD1, and survivin significantly decreased in baicalein-treated osteosarcoma cells, whereas exogenous expression of β-catenin could reverse the anti-proliferative and anti-metastatic effects of baicalein. Subsequently, we established a 143B xenograft tumor model and found that baicalein treatment significantly inhibited tumor growth accompanied with inhibiting Wnt/β-catenin pathway. Thus, these findings suggest that baicalein may be a potentially effective Chinese herbal medicine for therapeutics of osteosarcoma and Wnt/β-catenin signaling pathway may serve as an efficient molecular marker or predictive target for osteosarcoma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.