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Therapeutic Effect of Supercritical CO 2 Extracts of Curcuma Species with Cancer Drugs in Rhabdomyosarcoma Cell Lines
Author(s) -
Ramachandran Cheppail,
Quirin KarlW.,
Escalon Enrique A.,
Lollett Ivonne V.,
Melnick Steven J.
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5360
Subject(s) - curcuma , apoptosis , rhabdomyosarcoma , cell culture , ic50 , pharmacology , cytotoxicity , dna laddering , adjuvant , alveolar rhabdomyosarcoma , cytotoxic t cell , programmed cell death , chemistry , biology , medicine , traditional medicine , immunology , in vitro , dna fragmentation , pathology , biochemistry , sarcoma , genetics
Synergistic effect of supercritical CO 2 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 IC 50 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 p 53) and also inhibited the expression of genes associated with inflammation such as COX ‐2 and NF ‐κ B . 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.