Vitamin C and diallyl sulfide as chemosensitizers to cisplatin in treating hepatocellular carcinoma

Abstract

Background

The resistance to chemotherapy is a major obstacle in the treatment of hepatocellular carcinoma (HCC), necessitating the discovery of additional agents. The use of natural products in this respect is extensively under investigation.

Methods

Two hundred and ten male albino rats were used, divided into 14 groups. Selected groups were pre-treated with vitamin C (ascorbic acid, AA) and/or diallyl sulphide (DAS). Hepatocellular dysplasia was initiated by a single intra-peritoneal (IP) injection of diethyl nitrosamine (DENA), diabetes was induced by a single IP injection of Streptozotocin (STZ). Other groups were treated with cisplatin (CP) alone or combined with AA and/or DAS for 14 weeks. This work aims to check if naturally occurring materials can help in improving  response to CP  chemotherapy using ploylol profile as a new index in management of HCC.

Results

The results revealed that DENA significantly increased relative liver weight, serum ALT, AST and GGT activities, AFP, TNF-α and IL-6 levels, expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and Bcl2 proteins in the liver with decrease in body weight, expression of Bax protein and Bax/Bcl2 ratio in the liver.  These effects were more pronounced in DENA+STZ group. These parameters showed relative correlation to AFP levels in HCC, in response to AA and/or DAS treatment except for SDH. Treatment with CP and/or AA and/or DAS significantly modulated most of these parameters except for SDH which showed no significant change in response to the suggested treatment.

Conclusions

In conclusion, AA and/or DAS showed apparent chemo-sensitizing, anti-inflammatory, AR inhibitory, apoptotic inducing and anti-diabetic activities, indicating new aspects for use as adjuvant to chemotherapy.   Induction of diabetes in hepatocellular dysplasia -bearing rats showed higher resistance to chemotherapy. Ploylol profile is a useful prognostic tool in HCC patients with diabetic interference.