Evaluation of osteosarcoma cancer stem cells under hypoxia and its response with bezafibrate medroxy progesterone acetate

Abstract

Osteosarcoma is an aggressive pediatric bone cancer tumor prone to relapse despite surgery and chemotherapy It is a mesenchymal tumor derived from osteoblast lineage that has accumulated mutations in the cell cycle checkpoint for excessive proliferation Cancer Stem Cells CSCs exhibit chemo and radioresistance that accounts to tumor relapse owing to the incomplete eradication and a refractory population. In this study our current knowledge about osteosarcoma stem cells from Saos 2 osteosarcoma cell line highlights new insights into cancer therapeutics Targeting cancer stem cells in osteosarcoma is a promising avenue to explore new therapies for this devastating adolescent cancer Our studies focus on some of the metabolic attributes and stemness markers of cancer stem cells that are implicated in maintaining such cells and differences from paradigms of bone cancer The experiments were designed with CSCs CD133ve cells sorted from Saos 2 cells The results demonstrated that the CSCs exhibited quiescent cell proliferation in DNA doubling and cell cycle analysis We observed calcium signaling and membrane potential of cancer cells to be higher than cancer stem cells Gene expression of stemness genes SOX2 Oct4 and tumorigenic genes hTERT cMyc were elevated in CD133ve cells CSCs in hypoxia exhibited increased ATP production elevated glucose uptake than in normoxia Lactate Dehydrogenase LDH activity was expressed only in hypoxia of both the CD133veve cells Our novel findings revealed stemness and reverse Warburg effect of CSCs in Hypoxia Bezafibrate and medroxy progesterone acetate BAP effectively inhibited the proliferation of Saos2 and CD133veve cells in a dose and time dependent manner Morphological hallmarks of apoptosis such as chromatin condensation and DNA fragmentation were observed in BAP in normoxia and hypoxia treated groups newline