Assessment of Autophagy as Possible Mechanism of the Antitumor Effects of Arsenic Trioxide and/or Cisplatin on Ehrlich Ascites Carcinoma Model

Abstract

Arsenic trioxide (As2O3) (ATO) and cisplatin (CIS) have potent antineoplastic effects in several types of cancer. Autophagy is important for normal cell function and survival, it is also used by tumor cells so, we studied it's role as possible mechanism of ATO and/or CIS antitumor effect on mice bearing Ehrlich ascites carcinoma (EAC) and checked whether ATO can enhance the antitumor potential of CIS. The study was carried out on eight groups of female mice; GP1 (negative control), GP2 (Erlich tumor only), GP3 (Normal +ATO), GP4 (Normal + CIS), GP5 (Normal + ATO+CIS), GP6 (EAC+ATO), GP7 (EAC+CIS) and GP8 (EAC +ATO+ CIS). In this study, viable cells were counted, percentage of viability (%) was calculated. Flowcytometry of autophagosome was appointed. Glutathione S-transferase (GST) and catalase (CAT) enzymes activities, total thiol and malondialdehyde (MDA) concentrations in liver tissues were determined to evaluate the effects of these drugs. Treatment with ATO (GP6) induced a significant decrease in tumor volume and percentage of viability with best result in combination of ATO with low dose of CIS (GP8) against EAC. Our results showed that a reduction in flourscence intensity of autophagosome marker that determined by flowcytometry especially in combination treated group (GP8). CAT, GST enzymes activities and total thiol level were decreased, while MDA level was increased in ATO treated group (GP6) and CIS treated group (GP7) as compared to EAC group. On other hand, combining both ATO and CIS in EAC treated group (GP8) decreased MDA level and augmented the level of total thiol and activities of CAT and GST enzymes. Therefore, our result revealed that combination of ATO and CIS have anti-tumor effects against EAC better than each one alone. So, we recommended the combination of ATO with CIS treatment due to their synergetic effect on cancer