Sainz Rosa M, Reiter Russel J, Tan Dun-Xian, Roldan Francis, Natarajan Mohan, Quiros Isabel, Hevia David, Rodriguez Carmen, Mayo Juan C
Departamento de Morfología y Biología Celular, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Spain.
J Pineal Res. 2008 Oct;45(3):258-70. doi: 10.1111/j.1600-079X.2008.00585.x. Epub 2008 Apr 2.
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 hrTNFalpha induced cell death by decreasing NFkappaB activation. Bcl-2 and survivin down-regulation appears to be associated to apoptosis stimulation under NFkappaB inhibition. On the contrary, melatonin does not promote irradiation-induced cell death due to an increment in intracellular glutathione content. In conclusion, prevention of NFkappaB 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.
近年来，抗氧化剂在降低癌症发生和发展中的作用备受关注。抗氧化剂不仅能限制癌细胞的生长，而且在某些情况下，还能提高传统治疗方法的效果。褪黑素是一种内源性合成的抗氧化剂，在体内和体外均可降低多种肿瘤类型的细胞生长。此外，这种吲哚类物质还能限制许多化疗药物引起的附带损伤。通过使用人前列腺癌的细胞模型，我们研究了褪黑素增强肿瘤坏死因子或γ射线诱导的细胞凋亡的能力。据报道，褪黑素可降低前列腺癌细胞的生长，最近还发现它能促进细胞分化。在这项研究中，我们还表明褪黑素可提高p21蛋白水平，并增强前列腺癌细胞的抗氧化能力。此外，褪黑素通过降低NFκB的激活显著增强hrTNFα诱导的细胞死亡。Bcl-2和survivin的下调似乎与NFκB抑制下的凋亡刺激有关。相反，由于细胞内谷胱甘肽含量的增加，褪黑素不会促进辐射诱导的细胞死亡。总之，褪黑素对NFκB激活的抑制增强了细胞因子治疗前列腺癌细胞的效果，但不足以增强由其他产生自由基的疗法引发的细胞死亡。应仔细考虑谷胱甘肽在前列腺癌细胞存活机制中的关键作用。
