Highly cytotoxic gold(I)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Hai Van Le
  • Muhammad Ali Ehsan
  • Muhammad Altaf
  • Lisa Reichert
  • Artem L. Gushchin
  • Wee Han Ang
  • Anvarhusein A. Isab

Detail(s)

Original languageEnglish
Pages (from-to)7355-7363
Journal / PublicationDalton Transactions
Volume49
Issue number22
Online published8 May 2020
Publication statusPublished - 14 Jun 2020
Externally publishedYes

Abstract

Ovarian cancer is a highly aggressive disease which is treated by surgery and platinum chemotherapy. However, a significant proportion of treated patients develop resistance to platinum treatment resulting in tumor relapse. Acquired platinum resistance has been recently correlated with activation of pro-survival endoplasmic reticulum (ER) stress responses. We hypothesized that Au complexes that induce severe ER stress might counteract pro-survival cellular attempts leading to the ER stress-mediated apoptosis and reduced platinum resistance. In this work, we prepared a series of highly cytotoxic AuI-dialkyldithiocarbamate complexes and investigated their anticancer potential in ovarian cancer cells. Complexes demonstrated surprisingly low stability in chloroform, resulting in the formation of an Au chain polymer, which also displayed excellent cytotoxicity. Lead complex 2 induced oxidative stress and ER stress-mediated p53-independent apoptosis associated with PARP cleavage and cell cycle arrest at G2/M phase. Importantly, 2 caused the surface exposure of calreticulin (CRT), which is the first step in the activation of cellular immunogenic response.

Citation Format(s)

Highly cytotoxic gold(I)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells. / Le, Hai Van; Babak, Maria V.; Ehsan, Muhammad Ali; Altaf, Muhammad; Reichert, Lisa; Gushchin, Artem L.; Ang, Wee Han; Isab, Anvarhusein A.

In: Dalton Transactions, Vol. 49, No. 22, 14.06.2020, p. 7355-7363.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review