Celastrol Enhanced Doxorubicin‐Mediated Apoptosis in Saos‐2 Osteosarcoma Cells

BACKGROUND: Osteosarcoma is one of the most lethal types of human malignancy in the world. Natural compounds found in certain plant foods are considered chemotherapeutic agents that exert their effects through antiproliferative, proapoptotic, and pro-oxidant properties associated with cancer. OBJECTIVE: In this study, we investigated the effects of celastrol on the doxorubicin-mediated apoptosis in osteosarcoma cells. Saso-2 cancer cells were treated with ascending concentrations of doxorubicin and celastrol alone or in combination. METHODS: Cytotoxicity was measured using the MTT assay. Flow cytometry with Annexin V-FITC/PI double staining was performed to quantify apoptotic cell populations. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to measure the protein and mRNA expression levels of apoptosis mediators. An ELISA kit measured apoptosis. RESULT: In Saos-2 cells, celastrol enhanced the cytotoxic effects of doxorubicin. A combination of doxorubicin and celastrol had a more potent effect on apoptosis induction and modulation of mRNA and protein levels of key apoptotic mediators, including Bax, Bcl-2, caspase-3, cytochrome c, and p53. CONCLUSION: Overall, this study revealed that doxorubicin and celastrol could significantly potentiate doxorubicin-mediated apoptosis in osteosarcoma cells.