4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Combination of dihydroartemisinin and resveratrol effectively inhibits cancer cell migration via regulation of the DLC1/TCTP/Cdc42 pathway

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mechanism of DHA combined with RES in inhibition of cancer cell migration by DLC1/TCTP/Cdc42 signaling.

          Abstract

          Resveratrol (RES) is a polyphenolic plant antitoxin that increases the level of the tumor suppressor gene deleted in liver cancer 1 (DLC1) to suppress cancer progression. Dihydroartemisinin (DHA), a main active metabolite of anti-malarial drug artemisinin (ART), inhibits cancer cell invasion and migration by decreasing the translationally controlled tumor protein (TCTP), as reported in a few literature studies. Compelling evidence has shown that combination therapy with two or more compounds is more effective than treatment with a compound alone. However, the mechanism of combination of DHA and RES on inhibition of cancer cell migration has not been reported. In this study, our results showed that combination of DHA and RES, compared to each compound alone, synergistically inhibited migration along with the decrease of wound closures and F-actin formation in HepG2 and MDA-MB-231 cancer cells. This combination treatment up-regulated DLC1 and down-regulated TCTP expressions significantly. The two proteins were identified to colocalize in focal adhesions and form a complex. Depletion of DLC1 increased TCTP expression, and transfection with either GFP-DLC1-WT or GFP-DLC1-R718A (GAP-dead mutant) decreased the TCTP level markedly, indicating that DLC1 negatively regulated TCTP in a RhoGAP-independent manner. Furthermore, this combination treatment impeded the migration of HepG2 and MDA-MB-231 cancer cells via Cdc42 regulating JNK/NF-κB and N-WASP signaling pathways, and knockdown of DLC1 obviously increased the levels of Cdc42 and the molecules related to both signaling pathways in MDA-MB-231 cells. The combination also effectively inhibited the growth of xenograft tumors in an avian embryo model. In sum, we reveal a novel combination of DHA and RES that inhibits cancer cell migration by modulating the DLC1/TCTP axis to hinder the Cdc42 related signaling pathway. This combination treatment may be a promising therapeutic strategy to inhibit cancer cell migration by targeting DLC1 and TCTP.

          Related collections

          Author and article information

          Contributors
          Journal
          FFOUAI
          Food & Function
          Food Funct.
          Royal Society of Chemistry (RSC)
          2042-6496
          2042-650X
          November 18 2020
          2020
          : 11
          : 11
          : 9573-9584
          Affiliations
          [1 ]Shandong Provincial Key Laboratory of Animal Resistant Biology
          [2 ]School of Life Sciences
          [3 ]Shandong Normal University
          [4 ]Jinan
          [5 ]China
          Article
          10.1039/D0FO00996B
          33150340
          2e93ff9a-56c4-406c-b3b4-aed80e57dc1b
          © 2020

          http://rsc.li/journals-terms-of-use

          History

          Comments

          Comment on this article