Zamora Mónica, Ortega Juan Alberto, Alaña Lide, Viñas Octavi, Mampel Teresa
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona Diagonal 645, E-08028-Barcelona, Spain.
Exp Cell Res. 2006 Jun 10;312(10):1813-9. doi: 10.1016/j.yexcr.2006.02.014. Epub 2006 Mar 23.
We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy.
我们研究了全反式维甲酸（atRA）对HeLa细胞的凋亡和抗增殖作用。我们的结果表明，HeLa细胞对atRA的抗增殖作用比对其凋亡作用更敏感。此外，我们证明半胱天冬酶抑制可减轻细胞死亡，但不会改变atRA依赖的细胞增殖减少，这表明atRA诱导的凋亡与细胞增殖停滞无关。为了检查ANT蛋白是否介导了这些atRA效应，我们用编码单个ANT（腺嘌呤核苷酸转位酶1 - 3）的表达载体瞬时转染细胞。我们的结果显示，过表达ANT1和ANT3的HeLa细胞增加了它们对atRA的敏感性。因此，我们的结果不仅证明了ANT同工型的不同功能活性，也有助于更好地理解atRA作为癌症治疗中使用的抗肿瘤药物的特性。
