Suppression of histone deacetylase 3 (HDAC3) enhances apoptosis induced by paclitaxel in human maxillary cancer cells in vitro and in vivo.
Inclusion of chemotherapeutic drugs in treatment of patients with newly diagnosed head and neck cancer has improved response rates and prolonged median survival. Nevertheless, most patients with advanced head and neck cancer are destined to relapse and to develop resistance to initially used drugs such as paclitaxel. Consequently, it has been more important in cancer therapy to determine the molecular mechanisms that are related to cell-killing effects of anti-cancer agents or cancer resistance against them. Consequently, we examined whether abrogation of histone deacetylase 3 (HDAC3) expression by anti-sense oligonucleotides (ASOs) potentiates the efficacy of paclitaxel in human maxillary cancer IMC-3 cells. Here, we showed that paclitaxel-induced apoptosis was enhanced significantly by addition of ASOs for HDAC3 in cultured cells. Furthermore, paclitaxel-induced apoptosis in IMC-3 tumors transplanted in nude mice was enhanced significantly by administration of ASOs for HDAC3, thereby suppressing tumor growth. We provide new evidence that HDAC3 is a novel molecular target whose inactivation can potentiate the efficacy of anti-cancer drugs disrupting microtubules such as paclitaxel.
Narita
Norihiko
N
Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui, Japan. norihiko@u-fukui.ac.jp
Fujieda
Shigeharu
S
Kimura
Yuichi
Y
Ito
Yumi
Y
Imoto
Yoshimasa
Y
Ogi
Kazuhiro
K
Takahashi
Noboru
N
Tanaka
Takeshi
T
Tsuzuki
Hideaki
H
Yamada
Takechiyo
T
Matsumoto
Hideki
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008441:Maxillary Neoplasms / Q000201:enzymology*; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000099186:Histone Deacetylase 3
D000972:Antineoplastic Agents, Phytogenic; D006655:Histone Deacetylases; D017239:Paclitaxel; D050257:Tubulin Modulators; D000099186:Histone Deacetylase 3