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Melatonin potentiates chemotherapy induced cytotoxicity and apoptosis in ratpancreatic tumor cells     
Yazarlar
Abdülhadi Cihangir Uğuz
Süleyman Demirel Üniversitesi, Türkiye
Doç. Dr. Bilal ÇİĞ
Süleyman Demirel Üniversitesi, Türkiye
Javier Espıno
I Bejarano
Mustafa Nazıroğlu
Süleyman Demirel Üniversitesi, Türkiye
A B Rodriguez
J A Parıente
Özet
Melatonin has antitumor activity via several mechanisms including its antiproliferative and proapoptotic effects in addition to its potent antioxidant action. Thus, melatonin has proven useful in the treatment of tumors in association with chemotherapeutic drugs. This study was performed to evaluate the effect of melatonin on the cytotoxicity and apoptosis induced by three different chemotherapeutic agents, namely 5-fluorouracil (5-FU), cisplatin, and doxorubicin in the rat pancreatic tumor cell line AR42J. We found that both melatonin and the three chemotherapeutic drugs induce a time-dependent decrease in AR42J cell viability, reaching the highest cytotoxic effect after 48 hr of incubation. Furthermore, melatonin significantly augmented the cytotoxicity of the chemotherapeutic agents. Consistently, cotreatment of AR42J cells with each of the chemotherapeutic agents in the presence of melatonin increased the population of apoptotic cells, elevated mitochondrial membrane depolarization, and augmented intracellular reactive oxygen species (ROS) production compared to treatment with each chemotherapeutic agent alone. These results provide evidence that in vitro melatonin enhances chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor AR42J cells and, therefore, melatonin may be potentially applied to pancreatic tumor treatment as a powerful synergistic agent in combination with chemotherapeutic drugs.
Anahtar Kelimeler
melatonin, chemotherapy, cytotoxicity, apoptosis, AR42J cells
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı J Pineal Res.
Dergi ISSN 0742-3098
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 08-2012
BM Sürdürülebilir Kalkınma Amaçları
Atıf Sayıları
WoS 151
SCOPUS 151

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