Mechanism of antiproliferative action of a new d-secoestrone-triazole derivative in cervical cancer cells and its effect on cancer cell motility.

作者: Noémi Bózsity , Renáta Minorics , Johanna Szabó , Erzsébet Mernyák , Gyula Schneider

DOI: 10.1016/J.JSBMB.2016.06.013

关键词: HeLaApoptosisBiologyCell cycle checkpointCancer cellFlow cytometryMTT assayMolecular biologyCellCell culture

摘要: Abstract Cervical cancer is the fourth most frequently diagnosed tumor and leading cause of death in females worldwide. predominantly related with human papilloma virus (HPV) infection, oncogenic types being HPV-18 -16. Our previous studies demonstrated that some d -secoestrone derivatives exert pronounced antiproliferative activity. The aim current investigation was to characterize mechanism action -secoestrone-triazole (D-SET) on three cervical cell lines different pathological backgrounds. growth-inhibitory effects D-SET were determined by a standard MTT assay. We have found exerts effect HPV 18-positive HeLa HPV-negative C-33 A cells, but it has no substantial inhibitory activity 16-positive SiHa or intact fibroblast MRC-5 lines. After 24 h incubation, cells showed morphological biochemical signs apoptosis fluorescent double staining, flow cytometry caspase-3 Besides elevation ratio subG1 phase, cytometric analysis revealed cycle arrest at G2/M both To distinguish population immunocytochemical performed cells. results show significantly increases phosphorylated histone H3, indicating accumulation M phase. Additionally, increased maximum rate microtube formation measured an vitro tubulin polymerization its direct activity, antimigratory property been investigated. demonstrate inhibits migration invasion after incubation. These suggests potent agent against 16+ lines, efficacious motility-inhibiting Accordingly can be regarded as potential drug candidate promising new among steroids, potentially allowing for design novel anticancer agents.

参考文章(68)
R. Schlegel, P. M. Howley, Indira Krishnan-Hewlett, C. Yee, C. C. Baker, Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. American Journal of Pathology. ,vol. 119, pp. 361- 366 ,(1985)
Hatem A. M. Hejaz, Graham Packham, Atul Purohit, Paul A. Townsend, Barry V. L. Potter, Michael J. Reed, Lucy MacCarthy-Morrogh, Differential effects of estrone and estrone-3-O-sulfamate derivatives on mitotic. Arrest, apoptosis, and microtubule assembly in human breast cancer cells. Cancer Research. ,vol. 60, pp. 5441- 5450 ,(2000)
Wendell K, Jordan Ma, Wilson L, Copp H, Gardiner S, Derry Wb, Mitotic Block Induced in HeLa Cells by Low Concentrations of Paclitaxel (Taxol) Results in Abnormal Mitotic Exit and Apoptotic Cell Death Cancer Research. ,vol. 56, pp. 816- 825 ,(1996)
Renáta Minorics, Noémi Bózsity, Judit Molnár, János Wölfling, Erzsébet Mernyák, Gyula Schneider, Imre Ocsovszki, István Zupkó, None, A molecular understanding of D-homoestrone-induced G2/M cell cycle arrest in HeLa human cervical carcinoma cells. Journal of Cellular and Molecular Medicine. ,vol. 19, pp. 2365- 2374 ,(2015) , 10.1111/JCMM.12587
Torbjörn Bäckström, Shizhong Bu, Maréne Landström, Xin Fu, Li Li, Ulf Ulmsten, Induction of Apoptosis and G2/M Arrest by 2-Methoxyestradiol in Human Cervical Cancer HeLaS3 Cells Anticancer Research. ,vol. 24, pp. 873- 880 ,(2004)
A.O. Mueck, H. Seeger, 2-Methoxyestradiol—Biology and mechanism of action Steroids. ,vol. 75, pp. 625- 631 ,(2010) , 10.1016/J.STEROIDS.2010.02.016
Éva Frank, Judit Molnár, István Zupkó, Zalán Kádár, János Wölfling, None, Synthesis of novel steroidal 17α-triazolyl derivatives via Cu(I)-catalyzed azide-alkyne cycloaddition, and an evaluation of their cytotoxic activity in vitro. Steroids. ,vol. 76, pp. 1141- 1148 ,(2011) , 10.1016/J.STEROIDS.2011.05.002
Martin Sattler, Laura R. Quinnan, Yuri B. Pride, Jessica L. Gramlich, Stephanie C. Chu, Gaelle C. Even, Stine-Katherin Kraeft, Lan Bo Chen, Ravi Salgia, 2-Methoxyestradiol alters cell motility, migration, and adhesion Blood. ,vol. 102, pp. 289- 296 ,(2003) , 10.1182/BLOOD-2002-03-0729
Raffaella Ghittoni, The role of human papillomaviruses in carcinogenesis ecancermedicalscience. ,vol. 9, pp. 526- 526 ,(2015) , 10.3332/ECANCER.2015.526