2. Academic Validation
  3. VCPA, a novel synthetic derivative of α-tocopheryl succinate, sensitizes human gastric cancer to doxorubicin-induced apoptosis via ROS-dependent mitochondrial dysfunction

VCPA, a novel synthetic derivative of α-tocopheryl succinate, sensitizes human gastric cancer to doxorubicin-induced apoptosis via ROS-dependent mitochondrial dysfunction

  • Cancer Lett. 2017 May 1;393:22-32. doi: 10.1016/j.canlet.2017.02.007.
Han Wu 1,  Shaoping Liu 2,  Jun Gong 1,  Jiuyang Liu 1,  Qian Zhang 1,  Xiaohua Leng 3,  Nian Zhang 3,  Yan Li 4
Affiliations

Affiliations

  • 1 Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, China.
  • 2 Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, China.
  • 4 Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, China; Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, The Capital Medical University, Beijing, China. Electronic address: [email protected].
PMID: 28216375 DOI: 10.1016/j.canlet.2017.02.007
Abstract

Gastric carcinoma is a common malignant disease worldwide and has a dismal prognosis. Doxorubicin (DOX), one of the most widely used chemotherapeutic agents, has limited use because of its side effects and the development of tumor-cell resistance. Combinations of doxorubicin and non-cross-resistant agents have been required for adjuvant chemotherapy of gastric Cancer. Here, we report that VCPA, a novel synthetic derivative of α-Tocopheryl Succinate, induced Apoptosis via production of Reactive Oxygen Species (ROS). When used in combination with doxorubicin, lower doses of VCPA sensitized human gastric Cancer cells to DOX-induced Apoptosis. The DOX/VCPA combination treatment caused an imbalance in the ratio of Bcl-2 to Bax and induced a lethal mitochondrial dysfunction. MAPKs were also activated in response to the DOX/VCPA treatment but played a protective role in DOX-induced cell death. In vivo studies further confirmed the sensitizing effect of VCPA. Combining DOX with VCPA markedly inhibited tumor growth in a tumor xenograft model of human gastric Cancer. Taken together, our study revealed that VCPA, through increased ROS production, could synergize with DOX and circumvent DOX resistance in human gastric Cancer cells.

Keywords

Human gastric cancer; Mitochondrial apoptotic pathway; ROS.

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