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

Abstract

BackgroundThe 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. ResultsThe 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. ConclusionsIn 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.

Effect of co-administration of Bee honey and some chemotherapeutic drugs on dissemination of hepatocellular carcinoma in rats

“…This is attributed to the anti-proliferation effect of honey against induced HCC. Our result agrees also with Abdel-Hamid et al [76], Hemieda et al [123].…”

“…While, treatment with both honey and 5-FU showed improvement in cell structure with deficient collagen deposition. Our findings are in accordance with Abdel-Hamid et al [76], Cheng et al [125].…”

“…AFP is indicative for HCC; the decrease in its level suggested the inhibition in HCC development which is also supported by the improvement of liver function enzymes activity compared to HCC bearing rats. Our results are in concomitant also with Abdel-Hamid et al [76], who reported a significant decrease in AFP level compared to rats injected with sub carcinogenic dose of DEN, which reflected the response to cisplatin effect. Previously, Keam et al [77], observed the fall off in AFP level after cisplatin treatment and suggested that patients with HCC who did not show tumor response to radiographic treatment may response to cisplatin treatment.…”

“…The improvement in GGT level is also confirmed by the normalization in glutathione level. Also, Abdel-Hamid et al [76] observed that after IP injection with DEN there was marked elevation in GGT enzyme activity, this elevation is reduced post treatment with cisplatin. This may be due to the decrease in oxidative stress caused by DEN.…”

Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors

“…Nrf2 is an emerging regulator of cellular resistance to oxidants [103]. A combination of vitamin C and DAS was shown to offer several benefits, as inhibition of circulatory TNF-α and IL-6 in DENA-induced HCC in rats [104] and increases the sensitivity to chemotherapy as cisplatin in the treatment of HCC [105].…”