Open AccessImproved therapeutic efficacy against murine carcinoma by combining honokiol with gene therapy of PNAS‐4, a novel pro‐apoptotic gene
Author(s) -
Yuan Zhu,
Liu Huanyi,
Yan Fei,
Wang Yongsheng,
Gou Lantu,
Nie Chunlai,
Ding Zhenyu,
Lai Songtao,
Zhao Yuwei,
Zhao Xinyu,
Li Jiong,
Deng Hongxin,
Mao Yongqiu,
Chen Lijuan,
Wei Yuquan,
Zhao Xia
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01242.x
Subject(s) - honokiol , apoptosis , in vivo , angiogenesis , cancer research , lewis lung carcinoma , in vitro , genetic enhancement , pharmacology , medicine , immunology , biology , cancer , gene , biochemistry , metastasis , microbiology and biotechnology
PNAS‐4, a novel pro‐apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS‐4 (mPNAS‐4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS‐4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro , mPNAS‐4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS‐4 or honokiol alone, in vivo systemic administration of an expression plasmid encoding mPNAS‐4 and low‐dose honokiol significantly suppressed tumor growth through the enhanced induction of apoptosis and the augmented inhibition of angiogenesis. Our data suggest that the combined treatment with mPNAS‐4 plus honokiol augments antitumor effects in vitro and in vivo , and that the improved antitumor activity in vivo may be associated with enhanced induction of apoptosis and augmented inhibition of angiogenesis. The present study may provide a novel and effective method for the treatment of cancer. ( Cancer Sci 2009; 100: 1757–1766)