Article: Phloroglucinol derivative MCPP induces cell apoptosis in human colon cancer
| Title | Phloroglucinol derivative MCPP induces cell apoptosis in human colon cancer | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Huang, SM2 3 Cheung, CW1 Chang, CS2 Tang, CH2 Liu, JF2 Lin, YH2 Chen, JH4 Ko, SH Wong, KL1 2 3 Lu, DY | ||||||
| Issue Date | 2011 | ||||||
| Publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503 | ||||||
| Citation | Journal of Cellular Biochemistry, 2011, v. 112 n. 2, p. 643-652 [How to Cite?] DOI: http://dx.doi.org/10.1002/jcb.22966 | ||||||
| Abstract | This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (3,6-bis(3-chlorophenylacetyl)phloroglucinol; MCPP) in human colon cancer cells. MCPP induced cell death and antiproliferation in three human colon cancer, HCT-116, SW480, and Caco-2 cells, but not in primary human dermal fibroblast cells. MCPP-induced concentration-dependent apoptotic cell death in colon cancer cells was measured by fluorescence-activated cell sorter (FACS) analysis. Treatment of HCT-116 human colon cancer cells with MCPP was found to induce a number of signature endoplasmic reticulum (ER) stress markers; and up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein (GRP)-78, phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), suggesting the induction of ER stress. MCPP also increased GSK3alpha/beta(Tyr270/216) phosphorylation and reduced GSK3alpha/beta(Ser21/9) phosphorylation time-dependently. Transfection of cells with GRP78 or CHOP siRNA, or treatment of GSK3 inhibitor SB216163 reduced MCPP-mediated cell apoptosis. Treatment of MCPP also increased caspase-7, caspase-9, and caspase-3 activity. The inhibition of caspase activity by z-DEVE-FMK or z-VAD-FMK significantly reduced MCPP-induced apoptosis. Furthermore, treatment of GSK3 inhibitor SB216763 also dramatically reversed MCPP-induced GRP and CHOP up-regulation, and pro-caspase-3 and pro-caspase-9 degradation. Taken together, the present study provides evidences to support that GRP78 and CHOP expression, and GSK3alpha/beta activation in mediating the MCPP-induced human colon cancer cell apoptosis. © 2010 Wiley-Liss, Inc. | ||||||
| ISSN | 0730-2312 2011 Impact Factor: 2.868 2011 SCImago Journal Rankings: 0.379 | ||||||
| DOI | http://dx.doi.org/10.1002/jcb.22966 | ||||||
| ISI Accession Number ID | WOS:000287071900033
Funding Information: Grant sponsor: National Science Council; Grant numbers: 98-2320-B-039-009-MY2, 98-2627-B-039-005; Grant sponsor: China Medical University Hospital; Grant number: DMR-99-152. | ||||||
| References | References in Scopus |
| dc.contributor.author | Huang, SM | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Cheung, CW | ||||||
| dc.contributor.author | Chang, CS | ||||||
| dc.contributor.author | Tang, CH | ||||||
| dc.contributor.author | Liu, JF | ||||||
| dc.contributor.author | Lin, YH | ||||||
| dc.contributor.author | Chen, JH | ||||||
| dc.contributor.author | Ko, SH | ||||||
| dc.contributor.author | Wong, KL | ||||||
| dc.contributor.author | Lu, DY | ||||||
| dc.date.accessioned | 2011-09-23T05:42:19Z | ||||||
| dc.date.available | 2011-09-23T05:42:19Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.abstract | This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (3,6-bis(3-chlorophenylacetyl)phloroglucinol; MCPP) in human colon cancer cells. MCPP induced cell death and antiproliferation in three human colon cancer, HCT-116, SW480, and Caco-2 cells, but not in primary human dermal fibroblast cells. MCPP-induced concentration-dependent apoptotic cell death in colon cancer cells was measured by fluorescence-activated cell sorter (FACS) analysis. Treatment of HCT-116 human colon cancer cells with MCPP was found to induce a number of signature endoplasmic reticulum (ER) stress markers; and up-regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein (GRP)-78, phosphorylation of eukaryotic initiation factor-2alpha (eIF-2alpha), suggesting the induction of ER stress. MCPP also increased GSK3alpha/beta(Tyr270/216) phosphorylation and reduced GSK3alpha/beta(Ser21/9) phosphorylation time-dependently. Transfection of cells with GRP78 or CHOP siRNA, or treatment of GSK3 inhibitor SB216163 reduced MCPP-mediated cell apoptosis. Treatment of MCPP also increased caspase-7, caspase-9, and caspase-3 activity. The inhibition of caspase activity by z-DEVE-FMK or z-VAD-FMK significantly reduced MCPP-induced apoptosis. Furthermore, treatment of GSK3 inhibitor SB216763 also dramatically reversed MCPP-induced GRP and CHOP up-regulation, and pro-caspase-3 and pro-caspase-9 degradation. Taken together, the present study provides evidences to support that GRP78 and CHOP expression, and GSK3alpha/beta activation in mediating the MCPP-induced human colon cancer cell apoptosis. © 2010 Wiley-Liss, Inc. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Journal of Cellular Biochemistry, 2011, v. 112 n. 2, p. 643-652 [How to Cite?] DOI: http://dx.doi.org/10.1002/jcb.22966 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1002/jcb.22966 | ||||||
| dc.identifier.epage | 652 | ||||||
| dc.identifier.hkuros | 193530 | ||||||
| dc.identifier.isi | WOS:000287071900033
Funding Information: Grant sponsor: National Science Council; Grant numbers: 98-2320-B-039-009-MY2, 98-2627-B-039-005; Grant sponsor: China Medical University Hospital; Grant number: DMR-99-152. | ||||||
| dc.identifier.issn | 0730-2312 2011 Impact Factor: 2.868 2011 SCImago Journal Rankings: 0.379 | ||||||
| dc.identifier.issue | 2 | ||||||
| dc.identifier.pmid | 21268086 | ||||||
| dc.identifier.scopus | eid_2-s2.0-79251629978 | ||||||
| dc.identifier.spage | 643 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/138935 | ||||||
| dc.identifier.volume | 112 | ||||||
| dc.language | eng | ||||||
| dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503 | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Cellular Biochemistry | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Journal of Cellular Biochemistry. Copyright © John Wiley & Sons, Inc. | ||||||
| dc.subject.mesh | Cell Line, Tumor | ||||||
| dc.subject.mesh | Colonic Neoplasms - genetics - metabolism | ||||||
| dc.subject.mesh | Mediator Complex - genetics | ||||||
| dc.subject.mesh | Phloroglucinol - analogs and derivatives - pharmacology | ||||||
| dc.subject.mesh | Transcription Factor CHOP/genetics | ||||||
| dc.title | Phloroglucinol derivative MCPP induces cell apoptosis in human colon cancer | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- null
- China Medical University Hospital Taichung
- Buddhist Tzu-Chi General Hospital Taiwan