科研之友
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摘要
Topoisomerase II is a nuclear enzyme that alters DNA topology. It is a well-known anticancer target and related to cell differentiation status. All-trans retinoic acid (ATRA), an important active metabolite of vitamin A, is a promising anticancer agent in numerous malignancies. However, there are little data on the effect of retinoids on topoisomerase II regulation. In the present study, we investigated the relationship between ATRA and topoisomerase II, and the potential mechanisms of ATRA on topoisomerase II regulation. In several human carcinoma cell lines, ATRA was shown to suppress topoisomerase II protein, but not mRNA expression. ATRA induced the degradation of topoisomerase II through the proteasome pathway, but not the lysosome pathway. Ubiquitination was involved in this degradation. Western blot and immunocytochemistry proved that ATRA-induced topoisomerase II repression occurred only in the cell nuclei. ATRA not only influenced the cycle procession but also reduced the expression of cyclin D1. Cyclin D1, which is involved in cell differentiation, was regulated by topoisomerase II. Similar to cyclin D1, knockdown of topoisomerase II resulted in the increased differentiation of the cells, which was in contrast to the overexpression of topoisomerase II in the cells. Taken together, these data suggested that ATRA could target topoisomerase II and exert potential beneficial effects on cell differentiation.
- 出版日期2015-8
- 单位南京医科大学
