Basic scienceAntiproliferative and antiangiogenic activities of genistein in human renal cell carcinoma☆
Section snippets
Cell lines, cultures, and reagents
Four human RCC cell lines SMKT R-1, R-2, R-3, and R-4, which were established in our laboratory, were maintained in minimal essential medium with d-valine modification medium containing 10% fetal bovine serum. Each cell line was derived from a primary lesion of an individual patient with RCC. All cell lines were histopathologically proven to be of conventional RCC origin.12, 13 Genistein was obtained from Waco Pure Chemical Industries (Osaka, Japan).
Cell proliferation experiment
These four human RCC cell lines (3 × 103)
Effect of genistein on cell proliferation in human RCC cell lines
When the four human RCC cell lines, SMKT R-1, R-2, R-3, and R-4 were treated with several concentrations of genistein for 48 hours, it inhibited the growth of all four in a dose-dependent manner (Fig. 1A). A dose of 100 μg/mL genistein inhibited the growth in a time-dependent fashion (Fig. 1B; P <0.0001, Spearman rank correlation test).
Effect of genistein on apoptosis in human RCC cell lines
To determine the induction of apoptosis by genistein, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was performed. The
Comment
The inhibitory effect of genistein on the proliferation of cells in various cancers such as leukemia, neuroblastoma, rhabdomyosarcoma, prostate cancer, and bladder cancer has been reported in several studies.1, 3 For human RCC, only one study, by Balbaa et al.17 has reported that genistein suppresses the proliferation of SMKT R-3 cells, which we established. In the current study, genistein inhibited the proliferation of all four human RCC cell types in vitro, and this inhibition was both dose
Acknowledgements
To Drs. Taro Senba, Toshiaki Wakabayashi, Yasuhiro Funahashi, and Kentaro Yoshimatsu, Tsukuba Research Laboratories, Eisai Co., Ltd. for technical support.
References (28)
- et al.
Genistein, a dietary ingested isoflavonoid, inhibits cell proliferation and in vitro angiogenesis
J Nutr
(1995) - et al.
Tyrosine kinase inhibitor-induced differentiation of K-562 cellsalterations of cell cycle and cell surface phenotype
Cancer Lett
(1994) - et al.
Genistein, a specific inhibitor of tyrosine-specific protein kinase
J Biol Chem
(1987) - et al.
Effect of genistein on topoisomerase activity on the growth of [VAL 12] Ha-ras-transformed NIH3T3 cells
Biochem Biophys Res Commun
(1988) - et al.
Inhibition of human aromatase by mammalian ligands and isoflavonoid phytoestrogens
J Steroid Biochem Mol Biol
(1993) - et al.
Regulation of glycolipid sulfotransferase by tyrosine kinases in human renal cancer cells
Biochem Biophys Act
(1996) - et al.
Genistein inhibits proliferation similarly in estrogen receptor-positive and negative human breast carcinoma cell lines characterized by p21WAF1/CIP1 induction, G2/M arrest, and apoptosis
J Cell Biochem
(1998) - et al.
Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein
Cancer Res
(1990) - et al.
Inhibition of 17β-hydroxysteroid oxidoreductase by flavonoids in breast and prostate cancer cells
Proc Soc Exp Biol Med
(1998) - et al.
Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis
Cancer Res
(1998)
Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma
Br J Cancer
Markedly Increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis
Cancer Res
Establishment of three human renal cell carcinoma cell lines (SMKT-R-1, SMKT-R-2, and SMKT-R-3) and their characters
Urol Res
Study on in vitro invasive potential of renal cell carcinoma cell lines and effect of growth factors (EGF and TGF-β1)
Jpn J Urol
Cited by (43)
Renal cell carcinoma management: A step to nano-chemoprevention
2022, Life SciencesCitation Excerpt :Genistein is an isoflavone present abundantly in soybeans [134]. Genistein was found to prevent angiogenesis by downregulation of VEGF and basic fibroblast growth factor (bFGF) in RCC cell lines [135,136]. In vitro studies revealed that genistein induces cell apoptosis signifying its anti-proliferative activity [137,138].
Genistein inhibits angiogenesis developed during rheumatoid arthritis through the IL-6/JAK2/STAT3/VEGF signalling pathway
2020, Journal of Orthopaedic TranslationDesign, synthesis, and evaluation of the antiproliferative activity of hydantoin-derived antiandrogen-genistein conjugates
2018, Bioorganic and Medicinal ChemistryCitation Excerpt :Several studies have shown that genistein elicits pleiotropic effects, inhibiting and/or downregulating several cancer-relevant targets within the cell. Among the targets whose inhibition and/or downregulation has been implicated in the anti-proliferative activities of genistein include: tyrosine receptor kinases (TRKs), the TRK signal transduction pathway (TRK → Raf → MEK → ERK/p38), mitogen activated protein kinase signaling pathways (MAPKs)13,14, NF-kB15,16, Akt signaling16, human telomerase reverse transcriptase (hTERT)17, vascular endothelial growth factor (VEGF), platelet-derived growth factor, matrix metalloprotease-2 and -9 (MMP 2 and 9)18, and angiogenesis. Furthermore, genistein increases the expression of several histone acetyltransferases (HATs) in LNCaP and DuPro PCa cell lines as well as normal prostate epithelial cells.19
Anti-inflammatory action of γ-irradiated genistein in murine peritoneal macrophage
2014, Radiation Physics and ChemistryCitation Excerpt :In recent, it has been also used for development of biomolecules through the structural modification of its own structure (Bertok, 2005; Lee et al., 2005). Genistein is well known as a bio-functional material that is present in soy bean, and associate with prevention and therapy of various diseases, such as cancer, inflammation and oxidative damage (Sasamura et al., 2004; Farina et al., 2006). Especially, anti-inflammation activity of genistein was well reported that genistein treatment markedly attenuated ovalbumin (OVA) induced bronchoconstriction, pulmonary eosinophilia and airway hyper-responsiveness through the inhibition of a tyrosine kinase signaling cascade, and also shown to protective effect in rats from endotoxin induced organ failure, and later treatment with genistein reduced the degree of inflammation and joint destruction in collagen-induced arthriticmice (Duan et al., 2003).
Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention
2014, Cancer LettersCitation Excerpt :This compound is a strong anti-oxidant and a potent tyrosine kinase inhibitor. Other important mechanisms through which genistein exert its anti-cancer effects includes prevention of mutations in DNA strands; inhibition of cancer cell proliferation and angiogenesis; and proapoptotic effects [74–76]. Genistein has been found to be capable of modulating important epigenetic events, such as DNA methylation and histone tail modifications [77–79].
Genistein induces morphology change and G2/M cell cycle arrest by inducing p38 MAPK activation in macrophages
2014, International ImmunopharmacologyCitation Excerpt :This important compound possesses a variety of biological activities, for example as a phytoestrogen, an antioxidant, and as an inhibitor of a broad range of tyrosine kinases [1–3]. This leads to its chemoprotectant activities against chronic inflammatory disorders, cancers and cardiovascular disease [4–9]. The anti-inflammatory properties of genistein are a result of different mechanisms: Treatment with genistein can lead to inhibition of phospholipase A2, cyclooxygenases, and lipoxygenases resulting in the reduction of levels of pro-inflammatory mediators.
- ☆
This work was supported in part by a Grant-in-Aid from the Japanese Ministry of Education, Science, Sports and Culture, and the Stiftelsen Japanese-Swedish Cooperative Research Foundation.