Effects of melatonin on breast cancer cells

Autor: Ya -Yun Syu, 許雅雲
Rok vydání: 2010
Druh dokumentu: 學位論文 ; thesis
Popis: 98
Cancer is a leading cause of death worldwide. In America, one every nine women may develops breast cancer in her life time and it is the major form of cancer death among women around the world. Melatonin (MT) is a hormone secreted by the pineal gland. It regulates many physiological functions including sleep and wakefulness, body temperature, blood pressure, hormone productions, digestive secretion, and immune activity. It also inhibits cell proliferation and metastasis of breast cancer cells by suppressing estrogen receptor action. In this research, we investigate the effects of MT on non-estrogen dependent breast cancer cell lines, MDA-MB-231 and MDA-MB-231-IV4 and estrogen-dependent breast cancer cell line, MCF-7 with respect to cell number, cell viability, cell morphology changes and the cause leading to this effect. Our results indicated that cell number and cell viability of all three cancer cell lines were reduced by more than 50% and 80% after 72 hours of 1 mM and 3 mM MT treatment respectively. MT at 1 mM induced significant changes in cell morphology among MDA-MB-231 and MDA-MB-231-IV4 breast cancer cells. Treatment with MT receptors antagonist Luzindole or MT2 receptor antagonist 4P-PDOT, does not prevent melatonin-induced cell death suggesting that the is not depend on MT1/MT2 receptor activation. Detection of apoptotic cells by annexin V labeling in flow cytometry analysis revealed that there was an increase in 4% and 7% apoptotic cancer cells after 72 hours and 120 hours of 1 mM MT treatment respectively. As caspase-3 is a key effector in apoptotic pathway, we analyzed the expression of caspase-3 before and after MT treatment. Western blots analysis with specific caspase-3 antibodies indicated that indeed MT treatment induced significant changes in caspase-3 protein, supporting the previous finding in MCF-7 cancer cells where MT induced breast cancer cell death via apoptotic pathway. As MT is a naturally found substance in the nature and produced very little side effect, potentially it may provide the best anticancer drug. Further investigation is needed to support this hypothesis.
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