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Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation‐induced apoptosis in prostate cancer cells in vitro
Author(s) -
Sainz Rosa M,
Reiter Russel J.,
Tan DunXian,
Roldan Francis,
Natarajan Mohan,
Quiros Isabel,
Hevia David,
Rodriguez Carmen,
Mayo Juan C
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2008.00585.x
Subject(s) - melatonin , prostate cancer , cancer research , cancer cell , programmed cell death , apoptosis , tumor necrosis factor alpha , glutathione , cancer , biology , medicine , endocrinology , biochemistry , enzyme
The role of antioxidants in reducing cancer initiation and progression has been highlighted in recent years. Not only antioxidants limit cancer cell growth but also, in some situations, they promote the effectiveness of conventional treatments. Melatonin, an endogenously synthesized antioxidant, reduces cell growth of several tumor types both in vivo and in vitro. Additionally, the indole limits the collateral damage induced by many chemotherapeutic agents. By using a cellular model of human prostate cancer, we studied the ability of melatonin to enhance apoptosis induced by tumor necrosis factor or gamma radiation. It has been reported that melatonin reduces prostate cancer cell growth and, more recently, it promotes cell differentiation. In this work, we also show that melatonin elevates p21 protein levels and increases antioxidant capacity of prostate cancer cells. In addition, melatonin significantly enhances hrTNFα induced cell death by decreasing NFκB activation. Bcl‐2 and survivin down‐regulation appears to be associated to apoptosis stimulation under NFκB inhibition. On the contrary, melatonin does not promote irradiation‐induced cell death due to an increment in intracellular glutathione content. In conclusion, prevention of NFκB activation by melatonin enhances the effectiveness of cytokine treatment in prostate cancer cells but it is not sufficient to enhance cell death triggered by other therapies which generate free radicals. A crucial role of glutathione in survival mechanisms of prostate cancer cells should be carefully considered.