Highly cytotoxic gold(i)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells.
Hai Van LeMaria V BabakMuhammad Ali EhsanMuhammad AltafLisa ReichertArtem L GushchinWee Han AngAnvarhusein A IsabPublished in: Dalton transactions (Cambridge, England : 2003) (2021)
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.
Keyphrases
- cell cycle arrest
- endoplasmic reticulum
- cell death
- newly diagnosed
- immune response
- end stage renal disease
- free survival
- pi k akt
- chronic kidney disease
- sensitive detection
- ejection fraction
- minimally invasive
- dna damage
- anti inflammatory
- squamous cell carcinoma
- oxidative stress
- coronary artery bypass
- heart failure
- nitric oxide
- cell proliferation
- prognostic factors
- climate change
- endoplasmic reticulum stress
- peritoneal dialysis
- coronary artery disease
- inflammatory response
- acute coronary syndrome
- signaling pathway
- dna binding
- quantum dots
- patient reported outcomes
- atrial fibrillation
- single molecule