TY - JOUR
T1 - The p53-, Bax- and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones
AU - Qiu, Peiju
AU - Guan, Huashi
AU - Dong, Ping
AU - Li, Shiming
AU - Ho, Chi Tang
AU - Pan, Min Hsiung
AU - Mcclements, David Julian
AU - Xiao, Hang
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
KW - 5-Hydroxy polymethoxyflavones
KW - Bax
KW - Colon cancer
KW - P21
KW - P53
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U2 - 10.1002/mnfr.201000269
DO - 10.1002/mnfr.201000269
M3 - Article
C2 - 21462329
AN - SCOPUS:79953315359
SN - 1613-4125
VL - 55
SP - 613
EP - 622
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 4
ER -