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Study on the Molecular Mechanism of Apoptosis in Human Hepatoma Cell Line SMMC-7721 Cells Induced by Genistein

Author: WeiSiChen
Tutor: BaiWenYuan
School: Hebei Medical University
Course: Internal Medicine
Keywords: genistein hepatocellular carcinoma SMMC-7721 cells cell apoptosis apoptotic protein and gene
CLC: R735.7
Type: Master's thesis
Year: 2005
Downloads: 127
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Abstract

Primary hepatic carcinoma (PHC) is the most common primary hepatic tumor and one of the most common cancers worldwide, which has high morbidity and mortality. PHC has become the second killer of all malignant tumors in China. In resent years, there is a continuing increase in the incidence of PHC that threatens people’s health and life. The carcinogenesis of liver is influenced by environment and heredity through a set of factors and a series of steps. Up to now, surgical resection is still the main route but usually unsatisfied because hepatoma often accompanies by cirrhosis and early metastasis in liver. Chemotherapy is also unsatisfied because of its toxicity and side effects. Therefore, the current study focuses on finding noncelltoxical drugs which can suppress human hepatoma and improve the life quality of patients. Genistein is the important non-nutritious ingredient that is abundant in soybeans, fruits and other plants. It is not toxic to nomal cells. The lower frequencies of breast and prostate cancer in Asian population in general, compared to those in Western societies have been attributed to their consumption of relatively large amounts of soy products. Epidemiologic evidence strongly indicates that genistein, as an inhibitor of tyrosine protein kinase and plant estrogen, has a close relationship with the lower risk of cancers. It is indicated by a lot of animal tests and cell culture studies that genistein has some chemotective and chemotherapeutic potential against many tumors including prostate, breast, colon cancers. Several mechanisms have been proposed for the antitumor activity of genistein, which include the estrogenic and anti-estrogenic effects, apoptosis induction, modulation of cell cycle activity by arresting cell cycle at the G2/M stage, inhibition of DNA topoisomeraseⅡactivity which participates in DNA replication, transcription and repair, inhibiting the activity of protein tyrosine kinase(PTK)which is involved in phosphorylation of tyrosyl residues of membrane-bound receptors leading to signal transduction, inhibiting oxidative stress, antiangiogenesis and inhibition of tumor metastasis, inhibiting multi-drug resistance and so on. But the apoptosis induction is the main effect on tumor inhibition of genistein. As we all know, cell apoptosis plays an essential role in occurrence and development of PHC,which is also called programmed cell death. Apoptosis is induced by anticancer agents or death receptor agonists, which cause DNA damage, mitotic spindle dysfunction or metabolic perturbation. The apoptotic morphology can be observed through microscopy such as cells contraction, nuclear fragments, nuclear body formation and so on. In addition, DNA Ladder break also canbe detected by gel electrophoresis. Cell apoptosis is regulated through complex nets. Several cell apoptosis-related molecules are critically involved in the regulation of apoptosis, including Fas/FasL, Bcl-2 family which are made up of anti-apoptosis genes: Bcl-2、Bal-xL and apoptosis promoting genes such as Bax, Caspases family, apoptosis inhibiting protein such as survivin, antitumor gene p53 and others. The combination of Fas and FasL can obviously improve the induction of apoptosis. Bcl-2 family is the important apoptotic regulator, which can interdict the signals of many apoptotic passways. P53 is an important inhibiting gene that has two types: wild type and mutative type, wtp53 correlates closely with cell apoptosis and proliferation. P53 can repair DNA damage or induce apoptosis in DNA damaged cells. The mtp53 is significant in the development of many tumors including PHC because it loses the effect that is mentioned in wtp53. Survivin, as an important apoptosis inhibiting protein, has attached considerable attention over the past years because of its dual role in mitotic progression and apoptosis. This small protein (16 kilo daltons) is highly over-expressed in many types of cancer but nearly undetectable in normal differentiated adult tissues. Growing evidence indicates that survivin is over-expressed in PHC and

Study on the Molecular Mechanism of Apoptosis in Human Hepatoma Cell Line SMMC-7721 Cells Induced by Genistein

Abstract

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