1. Academic Validation
  2. Dihydroartemisinin potentiates antitumor activity of 5-fluorouracil against a resistant colorectal cancer cell line

Dihydroartemisinin potentiates antitumor activity of 5-fluorouracil against a resistant colorectal cancer cell line

  • Biochem Biophys Res Commun. 2018 Jun 27;501(3):636-642. doi: 10.1016/j.bbrc.2018.05.026.
Zhihan Yao 1 Adheesh Bhandari 1 Yinghao Wang 1 Yiyuan Pan 1 Fan Yang 1 Rongfa Chen 2 Erjie Xia 1 Ouchen Wang 3
Affiliations

Affiliations

  • 1 Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China.
  • 2 Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, 325035, China.
  • 3 Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China. Electronic address: woc863@hotmail.com.
Abstract

Although the combination of chemotherapy and surgical resection has effectively increased the survival rate of colorectal Cancer patients in recent decades, acquired drug resistance is still a problem that leads to treatment failure. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently been reported to show Anticancer effects against numerous types of Cancer, including colorectal Cancer. This study showed that DHA exerted a strong Anticancer effect against several colorectal Cancer cell lines. We also found that p53 knockout colorectal Cancer HCT116 cells (HCT116 TP53-/-) were not sensitive to 5-fluorouracil (5-FU) treatment, unlike wild-type HCT116 cells. Interestingly, co-treatment with DHA could effectively restore the Anticancer effect of 5-FU against HCT116 TP53-/- cells, which manifested as the inhibition of proliferation and induction of Reactive Oxygen Species (ROS)-mediated Apoptosis and was accompanied by the upregulation of B-cell lymphoma 2 (Bcl-2) and downregulation of the BCL-2-associated X protein (Bax). These findings suggested that DHA could effectively sensitize cells to 5-FU through ROS-mediated Apoptosis and the alteration of the Bcl-2/Bax expression ratio, which indicated that this may be one of the mechanisms of the DHA-promoted 5-FU Anticancer effect.

Keywords

5-Fluorouracil; Apoptosis; Colorectal cancer; Dihydroartemisinin; Reactive oxygen species; TP53 gene.

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