Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells

Abstract

Tangeretin (5,6,7,8,4'-pentamethoxyflavone) is concentrated in the peel of citrus fruits. DNA flow cytometric analysis indicated that tangeretin blocked cell cycle progression at G1 phase in colorectal carcinoma COLO 205 cells. Over a 24 h exposure to tangeretin, the degree of phosphorylation of Rb was decreased after 12 h and G1 arrest developed. The protein expression of cyclins A, D1, and E reduced slightly under the same conditions. Immunocomplex kinase experiments showed that tangeretin inhibited the activities of cyclin-dependent kinases 2 (Cdk2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. As the cells were exposed to tangeretin (50 microM) over 48 h a gradual loss of both Cdk2 and 4 kinase activities occurred. Tangeretin also increased the content of the Cdk inhibitor p21 protein and this effect correlated with the elevation in p53 levels. In addition, tangeretin also increased the level of the Cdk inhibitor p27 protein within 18 h. These results suggest that tangeretin either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins, such as Cdk2 and Cdk4, or mediates the increase of Cdk inhibitors p21 and p27.

Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer cells

“…The balance between survival-and apoptosis-signaling pathways controls tumor pathogenesis. A number of flavonoids exert potent antitumor activity through the induction of apoptosis and cell cycle arrest in several tumor cell lines (4,5). Flavonoids, a group of polyphenolic compounds, are natural products present in numerous fruits and vegetables and in all vascular plants (6).…”

Cytotoxic Effect From Ethyl Acetate-Methanol Subfraction of Carrisa Carandas L Toward Hela Cells by in Vitro Test

“…Triterpene can induce calcium (Ca 2+ ) which can stimulate cell death in tumor cells or cancer by blocking the cell cycle at the G2/M phase with stabilizing threads Spindle in the phase of mitosis so that the process of mitosis can be inhibited [14]. One class of flavonoids that alleged role in the cytotoxic effect was flavon or flavonol which can induce discontinuation phase G1 by damaging the DNA of cells [15]. The alkaloids can inhibit the enzyme activity of DNA topoisomerase II; an enzyme that plays an important role in the process of replication transcription, DNA recombination, and the proliferation of cancer cells that causes death by apoptosis [16].…”

Cell Cycle Arrest Effects by Artemisia annua Linné in Hep3B Liver Cancer Cell

“…선행연구에서 cell cycle에 관여 하는 Akt와 Mdm2의 활성이 p53과 Cdk2, Cyclin E 그리고 p21의 활성을 감소하는 것을 확인하였고 [18,19], 본 실험에 서 수행한 연구결과를 통하여 AAE가 Hep3B 간암세포에서 cell cycle에 관여하는 p-Akt와 p-Mdm2 신호분자의 활성을 감소시키고 p53과 CDK2, Cyclin E 억제제인 p21의 발현양이 증가하면서 Cyclin E의 발현양은 감소하는 것을 확인하였다. 또한 Cyclin E의 subunit인 phosphoform CDK2는 증가함을 확인하였다.…”