BCM-95® (CURCUGREEN®), 23 Mar 2017
Published on : Carcinogenesis . 2017 Oct 1;38(10):1036-1046. doi: 10.1093/carcin/bgx065.

Kazuhiro Yoshida, Shusuke Toden, Preethi Ravindranathan, Haiyong Han and Ajay Goel

Abstract: Development of resistance to chemotherapeutic drugs is a major challenge in the care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired resistance to chemotherapeutic agents in PDAC has been linked to a subset of cancer cells termed “cancer stem cells” (CSCs). Therefore, an improved understanding of the molecular events underlying the development of pancreatic CSCs is required to identify new therapeutic targets to overcome chemoresistance. Accumulating evidence indicates that curcumin, a phenolic compound extracted from turmeric, can overcome de-novo chemoresistance and re-sensitize tumors to various chemotherapeutic agents. Curcumin was also found to prevent the formation of spheroids, a hallmark of cancer stem cells, and to down-regulate several self-renewal driving genes. In addition, we confirmed our in vitro findings in a xenograft mouse

model where curcumin inhibited gemcitabine-resistant tumor growth. Overall, this study indicates clinical relevance for combining curcumin with chemotherapy to overcome chemoresistance in PDAC.

Methods: Following 48 hour treatment with curcumin and/or gemcitabine, total cellular protein was extracted and western immunoblotting was performed

Results: The mechanism of gemcitabine resistance in CSCs is consistent with those in gemcitabine chemoresistant cell lines. Moreover, the study demonstrated that the characteristics of acquired gemcitabine-resistant cells resembled those of pancreatic cancer stem-like cells. Collectively, these results highlight the possibility of using curcumin as a sensitizer to chemotherapeutic drugs in chemoresistant PDACs in the clinical settings.

Conclusion: In summary, using a series of in vitro and in vivo experiments, we have demonstrated that curcumin inhibits PRC2-PVT1-c-Myc, which enhances sensitivity of cancer cells to chemotherapeutic agents by targeting CSCs. Our data is consistent with previous studies and highlights the potential of curcumin as a promising therapeutic agent in pancreatic cancer. Moreover, mechanistic investigation of natural compounds such as curcumin could result in the development of safer and more potent chemotherapeutic agents. Further investigations including clinical trials are needed to confirm the efficacy of this compound as an adjuvant to chemotherapeutic regimens.

© The Author 2017. Published by Oxford University Press. All rights reserved. 

Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression – PubMed (nih.gov)

Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression (nih.gov) (Full text)

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