Minelli Alba, Bellezza Ilaria, Siciliano Emanuela, Liguori Lavinia, Tabarrini Oriana, Cecchetti Violetta, Fravolini Arnaldo
Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, Sezione Biochimica Cellulare, Università di Perugia, Via del Giochetto, 06123 Perugia, Italy.
Oncol Rep. 2005 Jun;13(6):1113-20.
Fluoroquinolones affect the proliferation and apoptotic cell death of several human malignancies. Therefore, we investigated whether new 6-aminoquinolone derivatives, initially synthesized as anti-HIV agents, could affect the proliferation and apoptotic cell death of human prostate cancer cell lines. PC3 and LNCaP cell lines were used as models of androgen-resistant and androgen-responsive prostate cancer, and proliferation of PC3 and LNCaP cells was strongly inhibited by 6-aminoquinolone WM13. Cytotoxicity, which was more pronounced in LNCaP, was accompanied by morphological changes, DNA damage, arrest at the S/G(2)/M phase of the cell cycle, and an increase of the sub-G(1) population. Molecular mechanism underlying WM13-induced cell death involved caspase-8 and -3 and modulation of the expression of apoptotic genes, as well as cleavage of poly-ADP ribose polymerase. Cell death following the treatment of human prostate cancer cell lines with WM13 can be attributed to apoptosis which, depending on the cell line, proceeds through different pathways.
氟喹诺酮类药物影响多种人类恶性肿瘤的增殖和凋亡性细胞死亡。因此，我们研究了最初作为抗HIV药物合成的新型6-氨基喹诺酮衍生物是否会影响人前列腺癌细胞系的增殖和凋亡性细胞死亡。PC3和LNCaP细胞系被用作雄激素抵抗性和雄激素反应性前列腺癌的模型，6-氨基喹诺酮WM13强烈抑制PC3和LNCaP细胞的增殖。细胞毒性在LNCaP中更为明显，伴有形态学改变、DNA损伤、细胞周期停滞于S/G(2)/M期以及亚G(1)期细胞群增加。WM13诱导细胞死亡的分子机制涉及半胱天冬酶-8和-3以及凋亡基因表达的调节，以及多聚ADP核糖聚合酶的裂解。用WM13处理人前列腺癌细胞系后的细胞死亡可归因于凋亡，根据细胞系的不同，凋亡通过不同途径进行。
