A molecular understanding of D-homoestrone-induced G2/M cell cycle arrest in HeLa human cervical carcinoma cells.

摘要: 2-Methoxyestradiol (ME), one of the most widely investigated A-ring-modified metabolites estrone, exerts significant anticancer activity on numerous cancer cell lines. Its pharmacological actions, including cycle arrest, microtubule disruption and pro-apoptotic activity, have already been described in detail. The currently tested d-ring-modified analogue d-homoestrone, selectively inhibits cervical proliferation induces a G2/M phase blockade, resulting development apoptosis. question arose whether difference chemical structures these analogues can influence mechanism action. aim present study was therefore to elucidate molecular contributors intracellular processes induced by d-homoestrone HeLa cells. Apoptosis triggered develops through activation intrinsic pathway, as demonstrated determination activities caspase-8 -9. It revealed that d-homoestrone-treated cells are not able enter mitosis because cyclin-dependent kinase 1-cyclin B complex loses its decreased inactivation stathmin concomitant disturbance formation. However, unlike 2-ME, does exert direct effect tubulin polymerization. These results led conclusion d-homoestrone-triggered arrest apoptosis differ from those case 2-ME. This may be regarded an alternative action among steroidal compounds.