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Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with Cancer Drugs in Rhabdomyosarcoma Cell Lines

Ramachandran, Cheppail, Quirin, Karl‐W., Escalon, Enrique A., Lollett, Ivonne V., Melnick, Steven J.
Phytotherapy research 2015 v.29 no.8 pp. 1152-1160
Curcuma amada, Curcuma longa, Curcuma zanthorrhiza, apoptosis, carbon dioxide, caspase-3, cell lines, cyclophosphamide, cytotoxicity, drug therapy, extracts, gene expression, humans, inflammation, inhibitory concentration 50, mice, neoplasms, patients, survival rate, synergism, transcription factor NF-kappa B, turmeric, vinblastine
Synergistic effect of supercritical CO₂ extracts of Curcuma species with conventional chemotherapeutic drugs was investigated in human alveolar (SJRH30) and embryonal (RD) rhabdomyosarcoma cell lines. The Curcuma amada (mango ginger) (CA) extract showed the highest levels of cytotoxicity with inhibitory concentration IC₅₀ values of 7.133 µg/ml and 7.501 µg/ml for SJRH30 and RD cell lines, respectively, as compared with Curcuma longa (turmeric) and Curcuma xanthorrhiza (Javanese 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 embryonal and alveolar rhabdomyosarcomas. When lower doses of CA (0.1–0.2 µg/ml) were combined with cancer drugs like CP and VBL, caspase‐3 activity increased significantly compared with individual agents and correlated with the percentage of apoptotic cells. CA in combination with VBL and CP induced a higher percentage of apoptosis than single agents in both cell lines. CA also modulated the expression of genes associated with intrinsic pathway of apoptosis (Bcl‐2, Bax, Bak, and p53) and also inhibited the expression of genes associated with inflammation such as COX‐2 and NF‐κB. Xenograft studies with SJRH30 tumors in nude mice showed that CA treatment inhibited tumor growth rate with and without VBL and increased the survival rate significantly. These results suggest that CA can be evaluated further as an adjuvant with cancer drugs for the treatment of rhabdomyosarcoma patients. Copyright © 2015 John Wiley & Sons, Ltd.