Adjuvant therapeutic use of supercritical-ethanol extracts of Curcuma species with cancer drugs in rhabdomycosarcoma cell lines

Rhabdomyosarcoma is a cancerous tumor that grows in the soft tissues of the body, particularly in the muscles that attach to bone and help the body to move. The two most common forms of this tumor are embryonal and alveolar, the latter being refractory and difficult to treat mainly because of cellular drug resistance. We investigated the synergistic effect of supercritical -ethanol extracts of Curcuma species along with conventional chemotherapeutic drugs in alveolar and embryonal rhabdomyosarcoma cell lines. Curcuma amada (mango ginger-CA) extract showed the highest levels of cytotoxicity as compared to C. longa (turmeric) and C. xanthorrhiza (Japanese turmeric) extracts. CA showed synergistic cytotoxic effects with vinblastine (VBL) and cyclophosphamide (CP), as indicated by the combination index values of <1 for VBL+CA, CP+CA and VBL+CP+CA combinations in both embryonic and alveolar rhabdomyosarcomas. When CA was combined with cancer drugs CP and VBL, caspase 3 activity increased significantly higher than that of individual agents which correlated with the percentage of apoptotic cells induced by the drugs and combinations. CA in combination with VBL and CP induced higher percentage of apoptosis than single agents in both cell lines. CA also induced significant quantitative changes in gene expression patterns (Bcl-2, Bax, Bak and p53) associated with intrinsic pathway of apoptosis. These results suggest that CA can be evaluated further as an adjuvant with cancer drugs for the treatment of rhabdomysarcoma patients.