Inhibition of cell proliferation and induction of apoptosis by genistein in experimental hepatocellular carcinoma

Chodon, Dechen; Banu, Syed Mumtaz; Padmavathi, R.; Sakthisekaran, Dhanapal

doi:10.1007/s11010-006-9324-2

Cited by 41 publications

(25 citation statements)

References 28 publications

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“…We also found that genistein induced cell cycle progression arrest at the G0/G1 and G2/M phases. These data are in accordance with other reports which showed that genistein induced cell cycle progression arrest at the G2/ M phase and that the number of S phase cells decreased in a progressive way as the genistein incubation time was increased [15,19,20] . Although the exact mechanisms of action of genistein have yet to be fully elucidated, induction of apoptosis may be partly responsible.…”

Section: Discussionsupporting

confidence: 93%

Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma

Gu¹,

Zhu²,

Dai³

et al. 2009

WJG

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AIM:To investigate the inhibitory effects of genistein on metastasis of MHCC97-H hepatocellular carcinoma cells and to explore the underlying mechanism. METHODS:MHCC97-H hepatocellular carcinoma cells were exposed to genistein. A cell attachment assay was carried out in a microculture well pre-coated with fibronectin. The invasive activity of tumor cells was assayed in a transwell cell culture chamber, and cell cycle and apoptosis were evaluated by a functional assay. In addition, the expression and phosphorylation of FAK were detected by Western blotting. In situ xenograft transplantation of hepatocellular carcinoma was performed in 12 nude mice and lung metastasis of hepatocellular carcinoma was observed. RESULTS:Genistein significantly inhibited the growth of MHCC97-H cells in vitro . Adhesion and invasiveness of MHCC97-H cells were inhibited in a concentrationdependent fashion, and the inhibitory effect of genistein was more potent in the 10 μg/mL and 20 μg/ mL genistein-treated groups. Genistein caused G0/G1 cell cycle arrest, an S phase decrease, and increased apoptosis. The expression and phosphorylation of FAK in MHCC-97H cells were significantly decreased. In situ xenograft transplantation of hepatocellular carcinoma was also significantly suppressed by genistein. The number of pulmonary micrometastatic foci in the genistein group was significantly lower compared with the control group (12.3 ± 1.8 vs 16.6 ± 2.6, P < 0.05).CONCLUSION: Genistein appears to be a promising agent in the inhibition of metastasis of hepatocellular carcinoma.

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Section: Discussionsupporting

confidence: 93%

Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma

Gu¹,

Zhu²,

Dai³

et al. 2009

WJG

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“…Because PCNA has been used as a proliferation index to reflect tumor growth because of its high levels in proliferating cells (55,(73)(74)(75), reduction of PCNA stability or acceleration of PCNA degradation might offer an effective strategy for regulating tumor growth. UV irradiation is a universal DNA-damaging factor, which acts mainly by inducing formation of DNA photoproducts between adjacent pyrimidine bases on the same strand such as cyclobutane pyrimidine dimers (CPDs) and (6 -4) photoproducts (6 -4PPs) (76).…”

Section: X-x-(a)-(a)]mentioning

confidence: 99%

Proliferating Cell Nuclear Antigen Is Protected from Degradation by Forming a Complex with MutT Homolog2

Cai

et al. 2009

Journal of Biological Chemistry

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Proliferating cell nuclear antigen (PCNA) has been demonstrated to interact with multiple proteins involved in several metabolic pathways such as DNA replication and repair. However, there have been fewer reports about whether these PCNAbinding proteins influence stability of PCNA. Here, we observed a physical interaction between PCNA and MutT homolog2 (MTH2), a new member of the MutT-related proteins that hydrolyzes 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP). In several unstressed human cancer cell lines and in normal human fibroblast cells, PCNA and MTH2 formed a complex and their mutual binding fragments were confirmed. It was intriguing that PCNA and MTH2 were dissociated dependent on acetylation of PCNA, which in turn induced degradation of PCNA in response to UV irradiation, but not in response to other forms of DNA-damaging stress. To further explore the link between dissociation of PCNA-MTH2 and degradation of PCNA, RNAi against MTH2 was performed to mimic the dissociated status of PCNA to evaluate changes in the half-life of PCNA. Knockdown of MTH2 significantly promoted degradation of PCNA, suggesting that the physiological interaction of PCNA-MTH2 may confer protection from degradation for PCNA, whereas UV irradiation accelerates PCNA degradation by inducing dissociation of PCNA-MTH2. Moreover, secondary to degradation of PCNA, UV-induced inhibition of DNA synthesis or cell cycle progression was enhanced. Collectively, our data demonstrate for the first time that PCNA is protected by this newly identified partner molecule MTH2, which is related to DNA synthesis and cell cycle progression.

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“…129 In fact, studies have found that genistein inhibits the growth of various cancer cell lines as a result of inhibition of protein tyrosine kinase activity. [137][138][139] The mechanism of these antiproliferative effects appears to be mediated through genistein's ability to inhibit NFB activation by the Akt or Notch-1 signaling axis. 139,140 However, genistein has also been shown to induce apoptosis through additional factors such as caspase-3 activation (an end-effector of apoptosis) and reduction in mitochondrial membrane potential.…”

Section: Phytoestrogensmentioning

confidence: 99%