Anticancer Effects of Combination of Indole-3-Carbinol and Hydroxychloroquine on Ehrlich Ascites Carcinoma via Targeting Autophagy and Apoptosis

Abstract

Indole-3-carbinol (I3C) is an active component of cruciferous vegetables which is considered a promising antineoplastic agent. This study aimed to assess I3C antineoplastic activity alone and with hydroxychloroquine (HCQ) on Ehrlich ascites carcinoma (EAC) model. Eighty female mice were divided into six groups wherein all groups except groups I and II received EAC cells (106 cells/mouse i.p.). Group I, served as control; group II served as I3C; group III served as EAC; groups IV and V received I3C (250 mg/kg body weight oral), and HCQ (60 mg/kg body weight i.p.) respectively; GVI received both I3C and HCQ. Antitumor response markers, serum, hepatic and renal biochemical parameters, histopathological changes, as well as autophagy and apoptosis markers in EAC cells were analyzed. The combination of I3C and HCQ showed the best antitumor responses with increased survival time and ameliorated biochemical parameters. Moreover, I3C upregulated LC3B and downregulated p62 gene expression in EAC cells. Furthermore, I3C combined with HCQ induced apoptosis by highly upregulating cleaved caspase-3 and Bax while downregulating Bcl-2 proteins expression in EAC cells in comparison with each drug alone. In conclusion, I3C combined with HCQ exhibited better antitumor activities than each drug alone via targeting autophagy and apoptosis.