Conflicting effects of caffeine on apoptosis and clonogenic survival of human K1 thyroid carcinoma cell lines with different p53 status after exposure to cisplatin or UVc irradiation.
Caffeine has been widely described as a chemo/radiosensitizing agent, presumably by inhibiting DNA repair, and affecting preferentially cells with an altered p53 status. We evaluated the effects of caffeine using isogenic and isophenotypic K1 cells derived from a papillary thyroid carcinoma and displaying either a wild type or a mutated p53 status. Apoptosis and clonogenic survival were examined after exposure of the cells to cisplatin or UVc irradiation. We find that at the most currently used concentration, 2mM, caffeine hinders cisplatin or UVc induced apoptosis in K1 cells. In addition, at this already barely achievable concentration in vivo, caffeine does not decrease their clonogenic survival. Hence in our cellular model, caffeine does not behave as a chemo- or a radiosensitizer. Although surprising, these results (1) are in agreement with the delayed G2/M block caused by caffeine that we previously observed in normal human fibroblasts and K1 cells and (2) allow us to elucidate some discrepancies concerning this molecule throughout the literature such as increase or decrease of apoptosis and clonogenic survival, activation or deactivation of molecules involved in DNA damage repair and proliferation inhibition but accelerated G2/M traverse.
Deplanque
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Altérations Génétiques des Cancers et Réponse Thérapeutique, UPRES-EA 3430, Laboratoire de Cancérologie Expérimentale et de Radiobiologie, Institut de Recherche contre les Cancers de l'Appareil Digestif, Hôpitaux Universitaires de Strasbourg, France.
Céraline
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J
Lapouge
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G
Dufour
P
P
Bergerat
J-P
JP
Klein-Soyer
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C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D013964:Thyroid Neoplasms / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002110:Caffeine; D002945:Cisplatin