Abstract
Objectives: To determine the effect of cis-9, trans-11-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and its possible mechanism of inhibition cancer growth.
Methods: Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B1, D1, p16ink4a and p21cip/waf1 of MCF-7 cells which were treated with various c9, t11-CLA concentrations (25 μM, 50 μM, 100 μM and 200 μM) of c9, t11-CLA for 24 and 48 h, with negative controls (0.1% ethanol).
Results: The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9, t11-CLA. MCF-7 cells, after treatment with various c9, t11-CLA doses mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively and the inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 μM, 24 h) incorporated significantly less 3H-TdR than did the negative control (P<0.05 and P<0.01). To further investigate the influence on the cell cycle progression, we found that c9, t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that MCF-7 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA, and Cyclin A, B1, D1 compared with the negative controls (P<0.01), whereas the expressions of p16ink4a and p21cip/waf1, cyclin-dependent kinases inhibitors (CDKI), were increased.
Conclusions: The cell growth and proliferation of MCF-7 cells is inhibited by c9, t11-CLA by blocking the cell cycle, which reduces expressions of cyclin A, B1, D1 and enhances expressions of CDKI (p16ink4a and p21cip/waf1).
