Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells

Zheng,Ruinian; You,Zhijian; Jia,Jun; Lin,Shunhuan; Han,Shuai; Liu,Aixue; Long,Huidong; Wang,Senming

doi:10.3892/mmr.2015.4715

Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells

Authors:
- Ruinian Zheng
- Zhijian You
- Jun Jia
- Shunhuan Lin
- Shuai Han
- Aixue Liu
- Huidong Long
- Senming Wang
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Affiliations: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Oncology, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China, Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Oncology, The Second People's Hospital of Shenzhen, Shenzhen, Guangdong 518035, P.R. China, Department of Internal Medicine, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
Published online on: December 24, 2015 https://doi.org/10.3892/mmr.2015.4715
Pages: 1570-1576
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

At present, the therapeutic treatment strategies for patients with hepatocellular carcinoma (HCC) remain unsatisfactory, and novel methods are urgently required to treat this disease. Members of the B cell lymphoma (Bcl)‑2 family are anti‑apoptotic proteins, which are commonly expressed at high levels in certain HCC tissues and positively correlate with the treatment resistance of patients with HCC. ABT‑737, an inhibitor of Bcl‑2 anti‑apoptotic proteins, has been demonstrated to exhibit potent antitumor effects in several types of tumor, including HCC. However, treatment with ABT‑737 alone also activates certain pro‑survival signaling pathways, which attenuate the antitumor validity of ABT‑737. Curcumin, which is obtained from Curcuma longa, is also an antitumor potentiator in multiple types of cancer. In the present study, the synergistic effect of curcumin and ABT‑737 on HCC cells was investigated for the first time, to the best of our knowledge. It was found that curcumin markedly enhanced the antitumor effects of ABT‑737 on HepG2 cells, which was partially dependent on the induction of apoptosis, according to western blot analysis and flow cytometric apoptosis analysis. In addition, the sustained activation of the ROS‑ASK1‑c‑Jun N‑terminal kinase pathway may be an important mediator of the synergistic effect of curcumin and ABT‑737. Collectively, these results indicated that the combination of curcumin and ABT‑737 can efficaciously induce the death of HCC cells, and may offer a potential treatment strategy for patients with HCC.

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