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Oncotarget. 2016 Dec 13;7(50):83641-83656. doi: 10.18632/oncotarget.13272.

Bisdemethoxycurcumin exerts pro-apoptotic effects in human pancreatic adenocarcinoma cells through mitochondrial dysfunction and a GRP78-dependent pathway.

Yang H1,2, Fan S1,2, An Y1,2, Wang X2, Pan Y1,2, Xiaokaiti Y1,2, Duan J1,2, Li X1,2, Tie L1,2, Ye M1,3, Li X1,2.

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State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.


Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC. Protein-protein interaction network analysis pinpoints glucose-regulated protein 78 (GRP78) as the key hub activated by BDMC. We then reveal that BDMC upregulates GRP78 and facilitates apoptosis through eIF2α/CHOP pathway. Moreover, DJ-1 and prohibitin, two identified markers of chemoresistance, are increased by gemcitabine in PANC-1 cells. This could be meaningfully reversed by BDMC, suggesting that BDMC partially offsets the chemoresistance induced by gemcitabine. In summary, these findings show that BDMC promotes apoptosis through a GRP78-dependent pathway and mitochondrial dysfunctions, and potentiates the antitumor effect of gemcitabine in human pancreatic cancer cells.


apoptosis; bisdemethoxycurcumin; gemcitabine; pancreatic cancer; proteomics

[Indexed for MEDLINE]
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