title: Sensitization of cervical carcinoma cells to paclitaxel by an IPP5 active mutant.
abstract: Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 (8-60hIPP5m), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of 8-60hIPP5m with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that 8-60hIPP5m enhances paclitaxel- induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to down- regulation of NF-?B activation and serine/threonine kinase Akt pathways. We noted that 8-60hIPP5m down- regulated the paclitaxel-induced NF-?B activation, I?Bα degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-?B. Together, our observations indicate that paclitaxel in combination with 8-60hIPP5m may provide a therapeutic advantage for the treatment of human cervical carcinoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, Guangxi, China E-mail : zengnn6@hotmail.com.
authors.forename: Qi-Yan
authors.initials: QY
authors.lastname: Zeng
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Lin-Jie
authors.initials: LJ
authors.lastname: Zeng
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Yong-Qi
authors.initials: YQ
authors.lastname: Huang
authors.forename: Qi-Fang
authors.initials: QF
authors.lastname: Zhu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004361:Drug Tolerance / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C547313:IPP5 protein, human; D016328:NF-kappa B; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D017239:Paclitaxel