Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines

Polkowski, Krzysztof; Popiołkiewicz, Joanna; Krzeczyński, Piotr; Ramza, Jan; Pucko, W.; Zegrocka-Stendel, Oliwia; Boryski, Jerzy; Skierski, Janusz; Mazurek, Aleksander P.; Grynkiewicz, Grzegorz

doi:10.1016/j.canlet.2003.08.023

Cited by 74 publications

(51 citation statements)

References 24 publications

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“…Genistein, an isoflavonoid abundant in soy beans, is a planar molecule with an aromatic A ring, has a second oxygen atom from that in the A ring, and has a molecular mass similar to those of the steroidal estrogens [9][10][11] . Reports from epidemiological and experimental studies show that it plays an important role in the inhibition of tumors including breast cancer, prostate cancer, colon cancer, leukemia and melanoma [12,13] . Genistein has a wide range of biological actions that suggest it may be of use in cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Genistein has a wide range of biological actions that suggest it may be of use in cancer treatment. Its molecular actions include: an inhibitory effect on protein tyrosine kinases, DNA topoisomerase Ⅰ and Ⅱ, and ribosomal S6 kinase; antiestrogenicity; antioxidant activity; anti-angiogenesis activity; suppression of cell proliferation; induction of differentiation and modulation of apoptosis [13][14][15] . However, few data are available on the effects of genistein on metastasis of HCC.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma

Gu¹,

Zhu²,

Dai³

et al. 2009

WJG

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show abstract

“…Nonetheless, we showed that all the cells showed chromosome abnormalities upon genistein treatment. Because genistein also inhibits the activity of topoisomerase II (reviewed in Polkowski et al 33 ), we have compared the effects of genistein and ICRF-193, which inhibits topoisomerase II catalytic activity. Our data reveal a couple of interesting findings.…”

Section: Discussionmentioning

confidence: 99%

Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe

Tominaga

Wang

et al. 2006

Cell Death Differ

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Epidemiological studies revealed that amount of consumption of soy was inversely related to incidence of breast cancer. Genistein, the predominant isoflavone in soy, has been reported to reduce the incidence of breast cancer in animal models. To investigate whether genistein has a therapeutic effect on BRCA1-associated breast cancer, we treated Brca1 mutant mammary tumor cells with genistein. We showed that genistein treatment depleted the G1 population of cells, which was accompanied by an accumulation of cells at G2. Some genistein-treated cells entered mitosis; however, they exhibited chromosome abnormalities and maintained tetraploidy owing to abortive mitotic exit. A fraction of G2 cells underwent endoreduplication and became polyploid, which was accompanied by increased cell death through activating DNA damage response. Furthermore, our data indicated that Brca1 mutant cells were more sensitive to genistein than some other types of cancer cells, highlighting a good therapeutic potential of genistein for BRCA1-associated breast cancer.

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“…Lipophilic drugs pass more easily through biological membranes than hydrophilic drugs, increasing their intracellular concentration and modulating signaling pathways, transcription factor activity, and gene expression (10,15). The genistein derivatives synthesized in this work showed different effects on NO, IL-12, and TNF-a production.…”

Section: Biological Evaluationmentioning

confidence: 96%

Synthesis of Lipophilic Genistein Derivatives and Their Regulation of IL‐12 and TNF‐α in Activated J774A.1 Cells

et al. 2012

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Genistein modulates inflammatory responses in part by reducing the production of the pro-inflammatory cytokines IL-12, TNF-a, and nitric oxide, by activated macrophages in response to lipopolysaccharide stimulus. Previous studies have shown that synthetic lipophilic genistein glycosides were significantly more active than hydrophilic glycosides. The aims of this study were to synthesize and to evaluate the effect of novel lipophilic genistein derivatives on IL-12, TNF-a, and nitric oxide production by J774A.1 cells. The results show that the modification of genistein enables the generation of non-cytotoxic compounds with increased IL-12 inhibition. However, these derivatives failed to inhibit TNF-a. The nitric oxide production was notably inhibited by the monoester (2, 3) and monoether (6, 7) compounds in a dose-dependent manner.

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Cytostatic and cytotoxic activity of synthetic genistein glycosides against human cancer cell lines

Cited by 74 publications

References 24 publications

Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma

Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma

Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe

Synthesis of Lipophilic Genistein Derivatives and Their Regulation of IL‐12 and TNF‐α in Activated J774A.1 Cells

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