Therapeutic Effect of Supercritical CO2 Extracts of Curcuma Species with Cancer Drugs in Rhabdomyosarcoma Cell Lines.
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.
Department of Pathology, Miami Children's Hospital, Miami, FL, 33155, USA.|Dharma Biomedical LLC, Miami, FL, 33156, USA.
Cheppail
C
Ramachandran
Flavex Naturextrakte GmbH, Rehlingen, Germany.
Karl-W
KW
Quirin
Division of Hematology/Oncology, Miami Children's Hospital, Miami, FL, 33155, USA.
Enrique A
EA
Escalon
Dharma Biomedical LLC, Miami, FL, 33156, USA.
Ivonne V
IV
Lollett
Department of Pathology, Miami Children's Hospital, Miami, FL, 33155, USA.|Dharma Biomedical LLC, Miami, FL, 33156, USA.
Steven J
SJ
Melnick
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry* / Q000145:classification; D003520:Cyclophosphamide / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012208:Rhabdomyosarcoma / Q000473:pathology*; D014747:Vinblastine / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010936:Plant Extracts; D014747:Vinblastine; C012596:turmeric extract; D003520:Cyclophosphamide; C505407:CASP3 protein, human; D053148:Caspase 3
Curcuma amada; apoptosis; gene expression; mango ginger; rhabdomyosaroma; xenografts