Melatonin potentiates chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor cells

:  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 evalu...

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Published in:Journal of pineal research 2012-08, Vol.53 (1), p.91-98
Main Authors: Uguz, Abdulhadi C., Cig, Bilal, Espino, Javier, Bejarano, Ignacio, Naziroglu, Mustafa, Rodríguez, Ana B., Pariente, José A.
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antioxidants - pharmacology
apoptosis
Apoptosis - drug effects
AR42J cells
Cell Line, Tumor
chemotherapy
Cisplatin - pharmacology
cytotoxicity
Doxorubicin - pharmacology
Fluorouracil - pharmacology
melatonin
Melatonin - pharmacology
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Rats
Time Factors
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Summary::  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.
ISSN:0742-3098
1600-079X
DOI:10.1111/j.1600-079X.2012.00974.x