Series Of Resveratrol Derivatives Effects On Cancer Cell Proliferation

Objective: To explore the inhibitory effects of a series of resveratrol derivatives in which fluorine atoms are induced on the growth of human cancer cells cultured in vitro, and further explore their anti-cancer mechanisms.Method: The MTT method was adopted to study and examine the inhibitory effects of this series of derivatives on proliferation of human colorectal cancer cells SW-480,gastric cancer cells SGC-7901 and breast cancer cells MDA-MB-231 that were cultured in vitro,thus to assess the selectivity regarding their effects on human colorectal cancer,gastric cancer and breast cancer cells. Meanwhile,the trypan blue counting method was used to observe the amounts of living and dead cells, thus to calculate the survival rate of cells, draw the cell growth curve and assess the inhibitory effect of the best derivative among this series of derivatives on the growth of human cancer cells; with the AO/EB staining method,morphological changes of apoptotic cancer cells induced by the best derivative among this series of derivatives were observed under fluorescent microscope;the degrees to which this kind of derivative induced the apoptosis of human cancer cells were analyzed and examined by PI staining and flow cytometry.Results: Using the MTT colorimetric method and taking the colorectal cancer cells SW-480,gastric cancer cells SGC-7901 and breast cancer cells MDA-MB-231 as its research objects,this experiment investigated the anti-cancer effects of 14 resveratrol derivatives;its results indicated that,after acting on the colorectal cancer cells,gastric cancer cells and breast cancer cells for 24 hours,all the 14 derivatives showed their inhibitory effects on the growth of breast cancer cells(MDA-MB-231),and the inhibitory effects of the drug y3-6 group were obviously stronger than other resveratrol derivative groups;among the 14 derivatives,most of them showed their inhibitory effects on the growth of gastric cancer,but drug y2-36,drug y3-1,drug y3-28 and drug y2-77 showed their promoting effects on the growth of gastric cancer cells(SGC-7901);apart from that drug y3-20 showed its inhibitory effect on the growth of colorectal cancer cells(SW-480),all the rest of this series of drugs showed promoting effects on its growth. It indicated that these 14 drugs had strong inhibitory effects on human breast cancer but didn’t work well with human gastric cancer and colorectal cancer,with selectivity for different cancer cells.Among the 14 resveratrol derivatives,the activity of derivative y3-6 was significantly stronger than that of resveratrol(Res);for human breast cancer cells,IC50 values of y3-6 and resveratrol were 34.39μM and 153.74μM,respectively. By 24 hours’ treatment of breast cancer cells with y3-6 at the concentration of 120μM,y3-6 had a relative inhibitory rate of78.5%,while relative inhibitory rates of Res and 5-Fu at the same concentration were 49.36% and 79.42%,proving that inhibitory effect of y3-6 on the growth of human breast cancer cells MDA-MB-231 was obviously stronger than that of Res and similar to that of 5-Fu. Under the same concentration,it showed promoting effect on the growth of colorectal cancer cells SW-480 and had a relative inhibitory rate of26.48% for gastric cancer cells SGC-7901,indicating that y3-6 had different effects on different cancer cells.Trypan blue counting showed that: By respectively culturing human breast cancer cells MDA-MB-231 with y3-6,Res and 5-Fu at a concentration of 20μM for 4 days and drawing the growth curve,it can be observed that inhibitory effect of y3-6 on the growth of breast cancer cells MDA-MB-231 was stronger than that of Res(with time independence) and similar to that of 5-Fu.AO/EB staining showed that: By culturing human breast cancer cells MDA-MB-231 with y3-6,Res and 5-Fu at all the concentrations of10μM、20μM、40μM for 24 hours respectively,it could be observed under fluorescent microscope that there were different levels of early and late apoptotic cells,with concentration-dependent apoptosis rate. Apoptosis rates of y3-6 were 7.06%,8.93% and 21.68%,respectively,higher than those of Res.PI staining and flow cytometry analysis showed that: Effect of y3-6on apoptosis of breast cancer cells MDA-MB-231 was concentration dependent;by culturing breast cancer cells MDA-MB-231 with y3-6 at concentrations of 10μM,20μM,40μM for 24 hours respectively,its apoptosis rates were 14.81±0.86%,15.93±0.09% and 33.67±1.15%,respectively,while under the same concentrations,apoptosis rates of Res were 7.65±0.33%,9.77±0.21% and 18.99±0.07%,indicating that apoptosis rate of y3-6 was higher than that of Res when at the same concentration.Conclusions:1.14 resveratrol derivatives have inhibition on human breast cancer MDA- MB- 231 cells proliferation activity,and y3-6 is the strongest inhibiting effect,its mechanism may be associated with y3-6 inducing tumor cell apoptosis.2.14 resveratrol derivatives,including 10 kinds of drugs that have inhibiting effect on the human gastric cancer SGC- 7901 cells,and the other four on human gastric cancer SGC- 7901 cells is to promote growth function.3.14 resveratrol derivatives,only y3-20 has inhibition impact on colon cancer SW-480 cells proliferation,and the other 13 kinds drug have promote effect.