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.
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 humancolon cancer cells. Herein, using isogenic variants of HCT116humancolon 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: M C Wei; W X Zong; E H Cheng; T Lindsten; V Panoutsakopoulou; A J Ross; K A Roth; G R MacGregor; C B Thompson; S J Korsmeyer Journal: Science Date: 2001-04-27 Impact factor: 47.728
Authors: W S el-Deiry; T Tokino; V E Velculescu; D B Levy; R Parsons; J M Trent; D Lin; W E Mercer; K W Kinzler; B Vogelstein Journal: Cell Date: 1993-11-19 Impact factor: 41.582