Enhancement of paclitaxel-induced apoptosis in HER2-overexpressing human breast cancer cells by a pertuzumab mimetic peptide, HRAP.
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.
Nakajima
Hiroo
H
Tsujigiwa Daigo Clinic, 1-19 Daigo Shinmachi-uramachi, Fushimi-ku, Kyoto 601-1326, Japan.
Mizuta
Naruhiko
N
Sakaguchi
Koichi
K
Fujiwara
Ikuya
I
Yoshimori
Atsushi
A
Magae
Junji
J
Tanuma
Sei-Ichi
S
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
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