The p53-, Bax- and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones.

Abstract

SCOPE:

Previously, we reported that 5-hydroxy polymethoxyflavones (5OH-PMFs) isolated from orange, namely 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone, 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF) and 5-hydroxy-6,7,8,4'-tetramethoxyflavone (5HTMF), potently induced apoptosis and cell-cycle arrest in multiple human colon cancer cells. Herein, using isogenic variants of HCT116 human colon cancer cells, we investigated the effects of p53, Bax and p21 on the apoptosis and cell-cycle arrest induced by different 5OH-PMFs.

METHODS AND RESULTS:

Annexin V/PI co-staining assay demonstrated that 5HHMF and 5HTMF significantly induced apoptosis in HCT116 (p53(+/+) ) cells but not in HCT116 (p53(-/-) ) cells. Furthermore, 5HHMF and 5HTMF significantly induced apoptosis in HCT116 (Bax(+/-) ) cells, whereas their pro-apoptotic effects on HCT116 (Bax(-/-) ) cells were marginal. All three 5OH-PMFs increased G0/G1 cell population of HCT116 (p53(+/+) ) cells, and these effects were abolished in HCT116 (p53(-/-) ) and HCT116 (p21(-/-) ) cells. Immunoblotting analysis showed that 5HHMF and 5HTMF increased the levels of cleaved caspase-3, cleaved PARP in both HCT116 (p53(+/+) ) and HCT116 (Bax(+/-) ) cells and these effects were much weaker in HCT116 (p53(-/-) ) and HCT116 (Bax(-/-) ) cells.

CONCLUSION:

Our results demonstrated that 5OH-PMFs, especially 5HHMF and 5HTMF, induce apoptosis and cell-cycle arrest by p53-, Bax- and p21-dependent mechanism.

• Authors: Peiju Qiu, Huashi Guan, Ping Dong, Shiming Li, Chi-Tang Ho, Min-Hsiung Pan, David Julian McClements, Hang Xiao
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 55 Issue 4 Pg. 613-22 (Apr 2011) ISSN: 1613-4133 [Electronic] Germany
• PMID: 21462329 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone
• 5-hydroxy-6,7,8,4'-tetramethoxyflavone
• Antineoplastic Agents, Phytogenic
• BAX protein, human
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Flavones
• TP53 protein, human
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• Caspase 3

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Colonic Neoplasms (drug therapy)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Flavones (pharmacology)
• HCT116 Cells
• Humans
• Osmolar Concentration
• Poly(ADP-ribose) Polymerases (metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)