Enhancement of paclitaxel-induced apoptosis in HER2-overexpressing human breast cancer cells by a pertuzumab mimetic peptide,HRAP |
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| Authors: | Hiroo Nakajima Naruhiko Mizuta Koichi Sakaguchi Ikuya Fujiwara Atsushi Yoshimori Junji Magae Sei-ichi Tanuma |
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| Affiliation: | 1 Tsujigiwa Daigo Clinic, 1-19 Daigo Shinmachi-uramachi, Fushimi-ku, Kyoto 601-1326, Japan;2 Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan;3 Department of Biochemistry, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan;4 Radiation Safety Research Center, Central Institute of Electric Power Industry, 2-11-1 Iwado-Kita, Komae-shi, Tokyo 201-8511, Japan |
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| 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. |
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| Keywords: | HRAP HER2 Paclitaxel Pertuzumab Breast cancer Apoptosis |
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