Phytomolecules and their analogues for targeting hepatocellular cancer

Project: Research project


Liver cancer is a most common, highly fatal and fifth most common cause of cancer death worldwide. Among the liver cancers 75% are primarily liver cell cancer. Hepatocellular carcinoma (HCC) is the cancer of hepatocytes and it is highly malignant among the adenomas which are epithelial or glandular cell origin. The etiology of HCC includes food toxins such as fungal aflatoxins or chronic hepatitis B/C infection. HCC is also because of progression of cirrhosis by chronic alcoholism, non-alcoholic steatohepatitis (NASH) or due to alpha-1-antitrypsin deficiency. Most importantly, HCC-patients have low survival rate after diagnosis and prognosis. Thus, pathogenesis involves many causes and numerous risk factors, the pharmacotherapy and disease-management of HCC is unsuccessful. A generalised HCC-management plan involves chemotherapy, radiotherapy, radiofrequency ablation (RFA), hepatectomy and liver transplantation. Present chemotherapy includes a MAP-Kinase inhibitor sorafenib, which is generally well tolerated. Sorafenib frequently exhibit intolerable adverse drug reactions which includes skin toxicities (hand-foot syndrome), GI-toxicities (diarrhoea), and hypertension apart from the general toxicities such as anorexia, alopecia, weight loss, and voice changes. Other chemotherapeutic agents used for palliative treatment are doxorubicin, 5-flurouracil (5-FU) and cisplatin. In comparison with all these modalities of treatments, the plant based medicine has less side effects, cost-effective and many of them efficacious. It was found the phytomolecules such as curcumin, resveratrol, many flavonoids and terpenes have very good anticancer activity. Our group have determined Zingiber zerumbet rhizome having significant anticancer activity both in cell lines as well as dienthylnitrosamine (DEN) induced hepatocellular cancer in rats. This activity was identified because of the phyto-constituent zerumbone in the rhizome. With this evidence, it is planned to isolate zerumbone in bulk from the rhizome. The isolated zerumbone can be targeted to hepatocellular cancer by nanoformulations with surface modification. The specific glycosamine conjugation which will have high binding ability to asialoglycoprotein receptor expressed in hepatocellular cancer. Further, the formulation can be explored in clinical trial once they are successful in animal models.
Short titlePhytomolecules for hepatocellular cancer
Effective start/end date01-10-1930-09-22