Departamento de Morfologia y Biologia Celular, Universidad de Oviedo, Oviedo, Spain Instituto Universitario Oncologico del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain Instituto de Ciencia y Tecnología de los Alimentos y Nutrición, ICTAN, CSIC, Madrid, Spain.
J Pineal Res. 2013 Jan;54(1):33-45. doi: 10.1111/j.1600-079X.2012.01017.x. Epub 2012 Jun 28.
Melatonin has antiproliferative properties in prostate cancer cells. Melatonin reduces proliferation without increasing apoptosis, and it promotes cell differentiation into a neuroendocrine phenotype. Because neuroendocrine cells displayed an androgen-independent growth and high resistance to radiotherapy and chemotherapy, the role of molecules that induce neuroendocrine differentiation was questioned in terms of their usefulness as oncostatic agents. By using human epithelial androgen-dependent and androgen-independent prostate cancer cells, the role of melatonin in drug-induced apoptosis was studied after acute treatments. In addition to cytokines such as hrTNF-alpha and TRAIL, chemotherapeutic compounds, including doxorubicin, docetaxel, or etoposide, were employed in combination with melatonin to promote cell death. Melatonin promotes cell toxicity caused by cytokines without influencing the actions of chemotherapeutic agents. In addition, antioxidant properties of melatonin were confirmed in prostate cancer cells. However, its ability to increase cell death caused by cytokines was independent of the redox changes. Finally, phenotypic changes caused by chronic treatment with the indole, that is, neuroendocrine differentiation, make cells significantly more sensitive to cytokines and slightly more sensitive to some chemotherapeutic compounds. Thus, melatonin is a good inhibitor of the proliferation of prostate cancer cells, promoting phenotypic changes that do not increase survival mechanisms and make cells more sensitive to cytokines such as TNF-alpha or TRAIL.
褪黑素对前列腺癌细胞具有抗增殖作用。褪黑素在不增加细胞凋亡的情况下抑制增殖，并促进细胞向神经内分泌表型分化。由于神经内分泌细胞表现出雄激素非依赖性生长和对放疗和化疗的高度耐药性，因此人们对诱导神经内分泌分化的分子在作为肿瘤抑制剂方面的作用提出了质疑。本研究使用人上皮雄激素依赖性和雄激素非依赖性前列腺癌细胞，研究了褪黑素在急性处理后对药物诱导的细胞凋亡中的作用。除了细胞因子如 hrTNF-α和 TRAIL 外，还将化疗药物，包括多柔比星、多西他赛或依托泊苷，与褪黑素联合使用以促进细胞死亡。褪黑素促进细胞因子引起的细胞毒性，而不影响化疗药物的作用。此外，抗氧化特性也在前列腺癌细胞中得到了证实。然而，其增加细胞因子引起的细胞死亡的能力与氧化还原变化无关。最后，慢性处理褪黑素引起的表型变化，即神经内分泌分化，使细胞对细胞因子（如 TNF-α或 TRAIL）更敏感，对某些化疗药物略敏感。因此，褪黑素是一种很好的前列腺癌细胞增殖抑制剂，可促进表型变化，而不会增加生存机制，并使细胞对 TNF-α或 TRAIL 等细胞因子更敏感。
