Cancer Letters

Cancer Letters

Volume 87, Issue 1, 25 November 1994, Pages 91-97
Cancer Letters

Reversion of the transformed phenotypes of v-H-ras NIH3T3 cells by flavonoids through attenuating the content of phosphotyrosine

https://doi.org/10.1016/0304-3835(94)90414-6Get rights and content

Abstract

Fifteen flavonoids were employed to examine their effects on the morphological changes, foci formation in soft agar and cellular growth in v-H-ras-transformed NIH3T3 cells. The data presented here demonstrated that only three specific flavonoids — apigenin, kaempferol, and genistein — exhibited the reverting effect on the transformed phenotypes of ras-3T3 cells. For example, treatment with 25 μM of these flavonoids could effectively reverse the transformed morphology of ras-3T3 cells into flatter cells with contact inhibition. Colony formation in soft agar was decreased to 0.11%, 0.15%, and 0.35% by 25 μM apigenin, kaempferol, and genistein, respectively, as compared with control (0.92%). It was also found that the proliferation of ras-3T3 cells was significantly inhibited by these compounds in a dose-dependent manner. Finally, two biochemical parameters, the content of phosphotyrosine and cAMP, were examined to see whether affected by these compounds. The results showed the phosphotyrosine content in ras-3T3 cells was dramatically decreased by apigenin and kaempferol, but that was slightly reduced by genistein. By contrast, these three flavonoids all failed to significantly alter the level of cAMP within this transformant. Based on these observations, we suggest that some specific flavonoids are capable of reverting the transforming properties of v-H-ras transformed cells. The possible mechanism of this reversion is not mediated by activating the protein kinase A or its associated pathways, but rather inhibiting tyrosine kinases, subsequently leading to the blockage of p21ras-mediated signal transduction circuitry.

Cited by (30)

  • Fabrication and characterization of bee pollen extract nanoparticles: Their potential in combination therapy against human A549 lung cancer cells

    2023, Food Hydrocolloids for Health
    Citation Excerpt :

    A longer survival time was connected to a lower level of RAS expression (Brosh & Rotter, 2009). Previously, several flavonoids such as apigenin, kaempferol, and genistein were found to reverse HRAS-transformed cell phenotypes, affecting proliferation, morphological changes, and colony formation (Kuo et al., 1994). Another flavonoid, resveratrol, inhibited cell proliferation and induced cell death, through p53 without direct modulation of the expression of both mRNA and the protein of mutant HRAS in the WR-21 cell line (Young et al., 2005).

  • Mitogen-induced rapid phosphorylation of serine 795 of the retinoblastoma gene product in vascular smooth muscle cells involves ERK activation

    2004, Journal of Biological Chemistry
    Citation Excerpt :

    Fig. 3 shows that phosphorylation of ERK and Rb was also blocked significantly by apigenin (50 μm). At this concentration, apigenin has been shown to arrest synchronized human diploid fibroblasts at the G0-G1 interface (31) and to block Ras-mediated activation of ERK (32, 33). In contrast, apigenin and PD98059 did not significantly affect the phosphorylation of MEK.

View all citing articles on Scopus
View full text