Ramachandran Cheppail, Nair Smitha M, Escalon Enrique, Melnick Steven J
Miami Children's Hospital, Miami, FL 33155, USA.
J Complement Integr Med. 2012 Aug 10;9:Article 20. doi: 10.1515/1553-3840.1614.
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.
我们研究了姜黄素(CUR)和姜黄制剂(TF)对U-87MG胶质母细胞瘤和D283髓母细胞瘤细胞系中依托泊苷(ETP)和替莫唑胺(TMZ)细胞毒性的增强作用,目的是评估它们在脑肿瘤化疗中辅助使用的潜力。虽然U-87MG细胞系通常对TMZ耐药,但CUR和TF的IC50值分别为37.33和30.75μg/ml。TF是唯一在IC90水平显示出疗效的药物。当CUR或TF与ETP和TMZ联合使用时,观察到U-87MG细胞的化疗效率提高。与姜黄素相比,TF对D283 Med细胞系具有高度细胞毒性,IC50值为1.55μg/ml。虽然CUR和TF都增强了ETP和TMZ的细胞毒性,但在U-87MG和D283 Med细胞系中,TF比CUR更有效。用TMZ+ETP+TF三联组合处理U-87MG细胞可诱导高比例的凋亡细胞。可能解释协同作用证据的潜在机制包括p10和p53 mRNA的下调以及BAX/Bcl-2 mRNA比值的增加。这些临床前结果表明,TF可能作为ETP和TMZ的辅助药物用于脑肿瘤化疗。