Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro

Rosa M. Sainz, Russel J Reiter, Dun Xian Tan, Francis Roldan, Mohan Natarajan, Isabel Quiros, David Hevia, Carmen Rodriguez, Juan C. Mayo

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)258-270
Number of pages13
JournalJournal of Pineal Research
Volume45
Issue number3
DOIs
StatePublished - Oct 2008

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Melatonin
Ionizing Radiation
Glutathione
Prostatic Neoplasms
Tumor Necrosis Factor-alpha
Apoptosis
Antioxidants
Cell Death
Growth
Neoplasms
Gamma Rays
In Vitro Techniques
Free Radicals
Cell Differentiation
Down-Regulation
Cytokines
Survival
Proteins

Keywords

  • Apoptosis
  • Glutathione
  • Melatonin
  • NFκB
  • Prostate cancer

ASJC Scopus subject areas

  • Endocrinology

Cite this

Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro. / Sainz, Rosa M.; Reiter, Russel J; Tan, Dun Xian; Roldan, Francis; Natarajan, Mohan; Quiros, Isabel; Hevia, David; Rodriguez, Carmen; Mayo, Juan C.

In: Journal of Pineal Research, Vol. 45, No. 3, 10.2008, p. 258-270.

Research output: Contribution to journalArticle

Sainz, Rosa M. ; Reiter, Russel J ; Tan, Dun Xian ; Roldan, Francis ; Natarajan, Mohan ; Quiros, Isabel ; Hevia, David ; Rodriguez, Carmen ; Mayo, Juan C. / Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro. In: Journal of Pineal Research. 2008 ; Vol. 45, No. 3. pp. 258-270.
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