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

Hai Van Le, Maria V. Babak, Muhammad Ali Ehsan, Muhammad Altaf, Lisa Reichert, Artem L. Gushchin, Wee Han Ang, Anvarhusein A. Isab

Результат исследования: Научные публикации в периодических изданияхстатья

Аннотация

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 complex2induced oxidative stress and ER stress-mediated p53-independent apoptosis associated with PARP cleavage and cell cycle arrest at G2/M phase. Importantly,2caused the surface exposure of calreticulin (CRT), which is the first step in the activation of cellular immunogenic response.

Язык оригиналаанглийский
Страницы (с-по)7355-7363
Число страниц9
ЖурналDalton Transactions
Том49
Номер выпуска22
DOI
СостояниеОпубликовано - 14 июн 2020

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