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In vitro activity of an anti-prostate cancer polypeptide APP216
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Abstract:
Objective: To investigate the in vitro the anti-prostate cancer effect of a novel polypeptide, APP216, so as to provide a basis for development of new drug for treatment of prostate cancer. Methods: The polypeptide drug included the amino sequences of BH3, K237 and DG2 domain and the peptide that could be digested by PSA. The anti-prostate cancer effects of the polypeptide prodrug on prostate cancer cell line LNCaP, 22RV1 (secreting PSA) and PC3, DU145 (secreting no PSA) were determined by MTT test and Hoechst 33258 staining. Results: MTT test revealed that the surviving rates of LNCaP and 22PV1 cells were respectively 22% and 34% 48 h after APP216 (270 μg/ml) treatment, and 9.8% and 8.2% 72 h after APP216 (270 μg/ml) treatment. The surviving rates of PC3 and DU145 cells were respectively 90% and 95% 48 h after APP216 (270 μg/ml) treatment, and 87% and 92% 72 h after APP216 (270 μg/ml) treatment. Hoechst 33258 staining showed the typical features of cell apoptosis: cell shrinkage, chromatin condensation and hypodiploid genomic DNA content in LNCaP and PC3m cells. Flow cytometry showed an apotosis rate of 36.26% 48 h after APP216 (270 μg/ml) treatment in LNCaP cells, and of 1.63% after 48 h APP216 (270 μg/ml) treatment in PC3m cells.Conclusion: APP216 has a satisfactory in vitro cytotoxicity on human PSA-secreting prostate cancer cells and can induce tumor cell apoptosis, but not on non-PSA secreting prostate cancer cells, indicating APP216 polypeptide can be specifically digested by endonuclease enzyme. Meanwhile, BH3 domain can be transferred into cells and induce apoptosis through HIV-TAT.
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