title: Enhancement of paclitaxel-induced apoptosis in HER2-overexpressing human breast cancer cells by a pertuzumab mimetic peptide, HRAP.
abstract: HRAP, a pentapeptide designed to bind with the pertuzumab interacting site in an extracellular domain of the HER2 molecule, enhanced the cytotoxicity of paclitaxel in HER2-overexpressing human breast cancer cell lines, BT474 and SKBR-3, but not in MDA-231 cells, which express lower levels of HER2. HRAP enhanced mitochondria-dependent apoptosis induced by paclitaxel in SKBR-3 and BT-474, but not in MDA-231. HRAP enhanced the inhibition of phosphorylation of serine 473 in Akt and Ser380/Thy382/The383 in PTEN. These results suggest that HRAP enhances paclitaxel-induced apoptosis in a manner dependent on the PTEN/Akt signal transduction pathway.
authors.affiliation: Tsujigiwa Daigo Clinic, 1-19 Daigo Shinmachi-uramachi, Fushimi-ku, Kyoto 601-1326, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakajima
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Mizuta
authors.forename: Koichi
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Fujiwara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshimori
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Tanuma
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D040761:Biomimetic Materials / Q000008:administration & dosage / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D017239:Paclitaxel / Q000008:administration & dosage; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004338:Drug Combinations; D009842:Oligopeptides; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; C553899:acetyl-prolyl-hisitidyl-alanyl-histidyl-phenylalaninamide; C508053:ERBB2 protein, human; C485206:pertuzumab