Apoptotic and anti-proliferative effects of all-trans retinoic acid. Adenine nucleotide translocase sensitizes HeLa cells to all-trans retinoic acid.
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.
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona Diagonal 645, E-08028-Barcelona, Spain.
Mónica
M
Zamora
Juan Alberto
JA
Ortega
Lide
L
Alaña
Octavi
O
Viñas
Teresa
T
Mampel
D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism*; D033781:Adenine Nucleotide Translocator 3 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D014212:Tretinoin / Q000494:pharmacology*
D033741:Adenine Nucleotide Translocator 1; D033781:Adenine Nucleotide Translocator 3; D000970:Antineoplastic Agents; D014212:Tretinoin