Anti-proliferative activity of constituent identified in cicada slough on human prostate cancer

Abstract

Prostate cancer (PC) is the most common malignancy and the second leading cause of male death in the United States and many European countries. In the Republic of Korea, the prevalence of prostate cancer has increased rapidly and the incidence rate is highest in total forms of malignancy. Reasons for the increases in prostate cancer incidence and mortality are unclear but may be explained in part by the gradual westernization of lifestyle. Hormonal therapy, chemotherapy, and radiotherapy have been used for prostate cancer treatment. Sometimes, serious side effects of these treatments occur, such as bleeding, hair loss, vomiting, and difficulty getting and maintaining an erection and a lowered sex drive. There is, therefore, a critical need for the development of new improved anticancer agents with novel target sites and low toxicity. In this study, an assessment is made of the anti-proliferative activity of cicada slough-derived materials against 10 human cancer cell lines, including PC-3 and DU145 prostate cancer cell lines, using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results were compared with those of the commercially available anticancer agent with broad spectrum cisplatin. The air-dried leaves (33 kg) of the cicada slough yielded 116.7 g of a dark greenish ethanol extract. The ethanol extract of Cryptotympana spp. slough was proved to have anti-proliferative activity against A549 lung, AGS stomach, PC-3 and DU145 prostate, Hela cervix, HT-29 colon, MCF-7 breast, and SK-Hep-1 liver cancer cell lines except for Hep-2 larynx and SK-OV-3 ovary cancer cell lines. The biologically active constituent was characterized as the nonprotein α-amino acid theanine [2-amino-4-(ethylcarbamoyl)butyric acid] by spectroscopic analysis, including EI-MS and NMR. Theanine was isolated from the cicada slough as a new cytotoxic principle. Fifty percent inhibition concentration (IC50) values of the constituent against PC-3 was 6.52 μg/mL, respectively. The activity of theanine (IC50, 6.52 μg/mL) did not differ significantly from that of the anticancer agent cisplatin (IC50, 7.39 μg/mL) toward PC-3. In conclusion, global efforts to reduce the level of antitcancer agents justify further studies on the cicada slough-derived materials containing theanine as potential anticancer products or a lead molecule for the prevention or eradication from human prostate cancer.