CKD712, a synthetic isoquinoline alkaloid, enhances the anti-cancer effects of paclitaxel in MDA-MB-231 cells through regulation of PTEN

被引:10
作者
Kim, Young Min [1 ]
Tsoyi, Konstantin [1 ]
Jang, Hwa Jin [1 ]
Park, Eun Jung [1 ]
Park, Sang Won [1 ]
Kim, Hye Jung [1 ]
Hwa, Jeong Seok [2 ]
Chang, Ki Churl [1 ]
机构
[1] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Pharmacol, Jinju 660751, South Korea
[2] Gyeongsang Natl Univ, Sch Med, Dept Urol, jinju 660751, South Korea
关键词
PTEN; NF-kappa B; Apoptosis; Invasion; Breast cancer; Paclitaxel; BREAST-CANCER CELLS; NF-KAPPA-B; SUPPRESSOR GENE; PHOSPHORYLATION; EXPRESSION; APOPTOSIS; (S)-1-(ALPHA-NAPHTHYLMETHYL)-6,7-DIHYDROXY-1,2,3,4-TETRAHYDROISOQUINOLINE; MATRIX-METALLOPROTEINASE-9; SENSITIVITY; INHIBITION;
D O I
10.1016/j.lfs.2014.07.015
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: It has been reported that in human glioblastoma cells, phosphotase and tensin homolog (PTEN) positive cells are more prone to paclitaxel-induced apoptosis than PTEN-negative cells. We investigated whether (S)-1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD712) enhances the therapeutic effects of paclitaxel (including effects on cellular proliferation, invasion and apoptosis) in MDA-MB-231 cells through PTEN and NF-kappa B activity. Main methods: Cellular proliferation, invasion and apoptosis were assessed by MIT, Western blot analysis, and TUNEL assay. Key findings: The combination of paclitaxel and CKD712 significantly decreased cell growth, invasion and MMP-9 expression/activity compared with paclitaxel alone. CKD712 enhanced the inhibition of cell growth and invasion in response to paclitaxel in scramble siRNA-transfected, but not siPTEN-transfected cells. CKD712 significantly increased the levels of apoptosis induced by paclitaxel and this apoptosis was accompanied by reduced expression of BcI-xI. but increased activation of caspase-3. TUNEL assay further confirms that CKD712 enhanced the apoptotic effect of paclitaxel. Interestingly, over-expression of PTEN decreased phosphorylation of I kappa B alpha and NF-kappa B expression in the nucleus, indicating that PTEN modifies NF-kappa B activity in MDA-MB-231 cells. CKD712 treatment also significantly reduced expression of p-I kappa B and NF-kappa B activity in TNF-alpha activated cells. Significance: CKD712 strongly enhances the anti-cancer effects (proliferation, invasion, and apoptosis) of paclitaxel on MDA-MB-231 cells by regulating PTEN and NF-kappa B activity. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:49 / 58
页数:10
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