Effects of Melatonin on Fine Structures and Extracellular Matrix Proteins of Cancer Cell Lines

Sung, Eon Ki; Jeong, Hyeon Gyoo; Song, In Hwan; Kim, Joo Young; Lee, Yungchang

Abstract

Melatonin could be used as an anticancer agent to suppress the proliferation of tumor cells and induce the differentiation of cancer cells. HeLa, HepG2, A549, L929, and NIH/3T3 cell lines were cultivated in alpha-MEM with 0.2 mM/2 mM melatonin. The influences of melatonin on quantitative changes of glycoprotein, fibronectin, laminin and actin related to the metastasis of tumor cells investigated with PAS or PAP at light microscopic level. To elucidate the possibility of antitumor actions of melatonin, the changes of cell organelles were observed under transmission electron microscope. Cell proliferation was suppressed after treatment with 2 mM melatonin for 2 or 3 days. Compared with control groups, the amounts of glycoprotein, fibronectin, laminin and actin in all cell lines at 1st, 2nd and 3rd day after treatment with 0.2 mM and 2 mM melatonin were generally increased. Heterochromatin in the nucleus formed clumps in all cell lines at 2nd and 3rd day after treatment with 0.2 mM and 2 mM melatonin. The numerical increase of rough endoplasmic reticulum and golgi complex observed in HeLa and L929 cells treated with 0.2 mM and 2 mM melatonin at 1st, 2nd and 3rd day. The number of lysosomes increased in HeLa, A549, and L929 cells treated with 0.2 mM and 2 mM melatonin at 3rd day. The number of vesicles increased in all cell lines treated with 0.2 mM and 2 mM melatonin at 1st, 2nd and 3rd day. Taken together, antimitotic effect of melatonin can be expected at least 2day after treatment with 2 mM melatonin. The production of fibronectin and laminin in all cell lines treated with 0.2 mM or 2 mM melatonin increased. Therefore, the increase of amounts of extracellular matrix proteins in the extracellular space can be expected. And the increase of amounts of actin connected to the extracellular matrix proteins through the integrin of plasma membrane seemed to strengthen cell attachment. In order to metastasize of cancer cells, it is important for them to secrete various enzymes to pass through the extracellular matrix proteins. Hence, it will be more difficult for the cells to metastasize into other regions due to the increase of the extracellular matrix proteins. It was postulated that the clumps of heterochromatin and the numerical increase of vesicles induced by treatment with 0.2 mM and 2 mM melatonin could be represented for the actions of melatonin as morpholgical criteria.