title: Potentiation of etoposide and temozolomide cytotoxicity by curcumin and turmeric force™ in brain tumor cell lines.
abstract: We have investigated on the potentiation of etoposide (ETP) and temozolomide (TMZ) cytotoxicity in U-87MG glioblastoma and D283 medulloblastoma cell lines by curcumin (CUR) and turmeric force (TF), a nutraceutical formulation of turmeric, with the objective of assessing the potential for their adjuvant use in brain tumor chemotherapy. While U-87MG cell line was generally resistant to TMZ, IC50 values for CUR and TF were 37.33 and 30.75 µg/ml, respectively. TF is the only agent that demonstrated efficacy at the IC90 level. When CUR or TF was combined with ETP and TMZ, increased chemotherapeutic efficiency in the U-87MG cells was observed. TF is highly cytotoxic to D283 Med cell line compared to curcumin with an IC50 value of 1.55 ug/ml. Although both CUR and TF potentiated ETP and TMZ cytotoxicity, TF is more efficient than CUR in both U-87MG and D283 Med cell lines. Treatment of U-87MG cells with the triple combination of TMZ+ETP+TF induced a high percentage of apoptotic cells. Potential mechanisms that may explain evidence of synergy include down regulation of p10 and p53 mRNAs and increase in BAX/Bcl-2 mRNA ratio. These pre-clinical results suggest that TF may be useful as an adjuvant with ETP and TMZ for brain tumor chemotherapy.
authors.affiliation: Miami Children's Hospital, Miami, FL 33155, USA. cheppail.ramachandran@mch.com
authors.forename: Cheppail
authors.initials: C
authors.lastname: Ramachandran
authors.forename: Smitha M
authors.initials: SM
authors.lastname: Nair
authors.forename: Enrique
authors.initials: E
authors.lastname: Escalon
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Melnick
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002528:Cerebellar Neoplasms / Q000188:drug therapy; D030024:Curcuma; D003474:Curcumin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D008527:Medulloblastoma / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage; D010946:Plants, Medicinal; D027343:Rhizome; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D005047:Etoposide; D003606:Dacarbazine; D003474:Curcumin; D000077204:Temozolomide