Synergistic Effect of Benzethonium Chloride Combined with Endoxan against Hepatocellular Carcinoma in Rats through Targeting Apoptosis Signaling Pathway

Document Type : Research Articles


1 Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, Egypt.

2 Health Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.

3 Radiation Biology, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.


Combination therapy has been the trendy of care, particularly in cancer remedy, since it is a rational approach to increase response and tolerability and to diminish resistance. Hence, there is a growing interest in combining anticancer drugs to maximizing efficacy with minimum systemic toxicity through the delivery of lower drug doses. Therefore, in the present study, the value of combination between benzethonium chloride (benzo) and endoxan (endo) as anti-tumor drug sensitization of hepatocellular carcinoma HCC treatment were detected both in vitro and in vivo. Crystal violet test was performed to detect the proliferation of HepG2 cells treated with benzo or/and endo. In addition, the HCC rat model was established by diethylnitrosamine (DEN) administration. The antitumor effect was enhanced with the combined treatment of the two drugs, particularly in the group with benzo and endo. The results confirmed that the HCC condition was developed in response to lower expressions of caspase 3 and P53 which, in turn, was due to the overexpression of Bcl-2, and downregulation of cytochrome C. The treatment with benzo combined with endo caused significant activation of caspase-3 mediated apoptotic signals that could be responsible for its anti-HCC potential. Meantime, benzo combined with endo treatments could reduce the hepatocellular carcinogenesis by reducing the expression of MMP-9. Therefore, benzo and endo treatments may be a hopeful therapeutic drug for HCC. Also, more studies are recommended to feat the idea of this research for medical use.


Main Subjects

Volume 21, Issue 6
June 2020
Pages 1709-1716
  • Receive Date: 05 February 2020
  • Revise Date: 27 April 2020
  • Accept Date: 22 June 2020
  • First Publish Date: 22 June 2020