The anti-tumor efficacy of c9, t11-CLA-PTX and t10, c12-CLA-PTX on MCF-7 breast cancer cells: in vitro and in vivo

doi:R965, R943

Abstract

Abstract:

Considering the results of our previous research that conjugated linoleic acid mixture-paclitaxel (CLA-mixture-PTX) possesses anti-tumor activity against melanoma and brain glioma, the purpose of this study was to investigate the potential anti-tumorefficacy of cis-9, trans-11-conjugated linoleic acidpaclitaxel (c9, t11-CLA-PTX) and trans-10, cis-12-conjugated linoleic acidpaclitaxel (t10, c12-CLA-PTX) on MCF-7 breast cancer cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis induction effect and cell cycle arresting effect of c9, t11-CLA-PTX and t10, c12-CLA-PTX were investigated. The in vitro cellularuptake of c9, t11-CLA-PTX and t10, c12-CLA-PTX in MCF-7 cells were also analyzed. Besides, the anti-tumor activity of c9, t11-CLA-PTX and t10, c12-CLA-PTX was evaluated in MCF-7 tumor bearing nude mice in vivo. The in vitro cytotoxicityresults showed that the value of IC₅₀ of the t10, c12-CLA-PTX is (0.17±0.02) µM, compared with that of (1.08±0.15) µM in CLA-mixture-PTX and (6.50±1.20) µM in c9, t11-CLAPTX treatment group (P<0.01). Both t10, c12-CLA-PTX and c9, t11-CLAPTX increased the percentage of total apoptotic cells compared with that of control (P<0.01). And the rank of apoptosis induction efficacy was t10, c12-CLA-PTX>CLA-mixture-PTX>c9, t11-CLAPTX (P<0.01). Compared with untreated cells, the t10, c12-CLA-PTX and c9, t11-CLAPTX arrested cell cycle progression at the S and G₂–M phase. The amount of cellular uptake of t10, c12-CLA-PTX was significantly higher than that of CLA-mixture-PTX (P<0.01), which was significantly higherthan that of c9, t11-CLAPTX (P<0.01). The rank of in vivo anti-tumor activity was t10, c12-CLA-PTX>CLA-mixture-PTX> c9, t11-CLAPTX (P<0.01). In conclusion, our study demonstrated that both t10, c12-CLA-PTX and c9, t11-CLAPTX has significant anti-tumor activity in MCF-7 cell line. And while c9, t11-CLAPTX showed weaker inhibitory effect than CLA-mixture-PTX, stronger inhibitory effect was presented by t10, c12-CLA-PTX, which could be a promising alternative for CLA-mixture-PTX.

Key words: c9,t11-CLAPTX, t10,c12-CLA-PTX, Apoptosis, Cell cycle, Cellular uptake, Anti-tumor efficacy

CLC Number:

10.5246/jcps.2014.11.095

Supporting:

Ke Yang, Xinghuo Li, Dan Li, Xiyu Ke, Xuan Zhang, Qiang Zhang. The anti-tumor efficacy of c9, t11-CLA-PTX and t10, c12-CLA-PTX on MCF-7 breast cancer cells: in vitro and in vivo[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(11): 751-759.

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