zerumbone and Liver-Neoplasms

Cancer is the uncontrolled proliferation of abnormal cells in the body. There is a foreseeable need for an effective anti-carcinogenic drug. In this regard, zerumbone (ZER) is identified as one such therapeutic herbal compound that has been shown to enhance the anticancer activity of cisplatin (CIS), with negligible side effects. Yet, the fundamental mechanisms of co-treatment of ZER and CIS on Hepatocellular carcinoma remain indefinable. The current study is endeavored to evaluate the anti-cancer effect of the individual and co-treatment of ZER, CIS and its combination on Diethyl nitrosamine induced hepatic cancer in wild-type zebra fish (Danio Rerio) models. Our careful analysis on treated and untreated fishes shows that CIS + ZER combination group restricted further progression of hepatocellular carcinoma cells significantly, which concludes that co-treatment of ZER with CIS was therapeutically effective for treating human HCC cancer cells which were induced into zebra fish.

Topics: Animals; Carcinoma, Hepatocellular; Cisplatin; Diethylnitrosamine; Fresh Water; Humans; Liver Neoplasms; Sesquiterpenes; Zebrafish

Zerumbone (ZER) exerts potent antiproliferative, apoptotic, and antiangiogenic functions against variety of cancer cells. Cisplatin (CIS), a standard chemotherapeutic drug, is effective against different types of cancers. However, the combined effect of ZER and CIS on hepatocellular carcinoma remains unknown.. The present study is attempted to examine the effectiveness of the combination of ZER and CIS in liver cancer in vitro using the hepatocellular carcinoma Huh-7 cell line.. Effect of ZER, CIS, and their combination therapy on cell viability and cytotoxicity was assessed by MTT and LDH leakage assays. Cell cycle and apoptosis analysis were performed by flow cytometry. Quantitative real-time PCR was used to examine the m-RNA expression of genes involved in apoptosis, angiogenesis, and invasion. Caspase activity was studied using commercial kit method in the Huh-7 cell line.. Cells exposed to ZER, CIS individually, and both together significantly inhibited cell proliferation with IC50 values of 10 μM for ZER and 3 μM for CIS. The combination treatment of ZER and CIS revealed a synergistic effect with a CI value < 1. CIS treatment, either alone or in combination with ZER, caused cell cycle arrest in the S phase. More importantly, ZER combined with CIS exhibited synergistic effects in up-regulating Bax/Bcl-2 ratio, leading to caspase cascade activation.. In conclusion, the current study indicates that the treatment of 4.62 μM of ZER combined with 1.93 μM of CIS in human liver cancer cells exerts synergistic effects on cell growth inhibition, apoptosis induction, angiogenesis, and invasion by modulating gene expression.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Caspases; Cell Line; Cell Line, Tumor; Cell Proliferation; Cisplatin; Humans; Liver Neoplasms; Sesquiterpenes

Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P<0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P<0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P<0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P<0.05) lowered. By the TUNEL assay, there were significantly (P<0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.

Topics: 2-Acetylaminofluorene; Animals; Anticarcinogenic Agents; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Hepatocellular; Chemoprevention; Diethylnitrosamine; Gene Expression Regulation, Neoplastic; Liver; Liver Neoplasms; Male; Malondialdehyde; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Rhizome; Serum; Sesquiterpenes; Zingiber officinale