Towards an Understanding of Specific Response of Metallothionein (Sub)Isoforms to Exposure to Platinum-Based Anticancer Drugs

Abstract

Metallothioneins (MTs) are small cysteine-rich proteins involved in a number of pathophysiological processes. Particularly their linkage to cancer processes has been vastly studied and it is well known that MTs can inactivate metal-based cytostatics or scavenge free radicals. These processes result in pronounced chemoresistance and a poor prognosis for patients. Despite this knowledge, involvement of specific (sub)isoforms into this phenomenon requires further elucidation. Our results identified CisPt as the cytostatic which provoked the highest cell death exp followed by CarboPt and OxaliPt. Fluorescence microscopy visualized the oxidative cell stress. After application of 24hIC50 values, the reactive oxygen species (ROS) were visually produced. Our results also showed that MT 1, 2 and 3 expression manifested the highest qPCR activity after CisPt treatment (both healthy and cancer cells). While evaluating the expression of the protein level in the healthy and cancer cells treated by the cytotoxics we concluded that for MT1 and MT3 it was low under all three cytostatic treatments. Cancer cells had higher protein expression levels than healthy cells. In case of MT1/2 for cancer cells was highest under CisPt treatment.

Keywords

• Cancer treatment
• metal-based cytostatic
• metallothioneins
• mRNA and protein expression
• qPCR activity