Studies on the inhibition of invasion and induction of apoptosis by methylselenol in B16F10 melanoma = 메틸셀레놀에 의한 암세포 침윤 억제와 세포 사멸 유도에 대한 기작 연구

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Melanoma cells, highly metastatic cancer cells, are resistant to the both procedures of chemotherapy and radiotherapy. Studies have shown that interactions between cancer cells and the extracellular matrix (ECM) are critical in the survival and invasion of metastatic cancer cells, facilitating resistance of the cancer cells to chemotherapy. Anti-cancer effect of selenium compounds and their biochemical pathways, leading to the induction of programmed cell death have been extensively studied. However, biochemical roles of selenium compound on the inhibition of metastasis and its detailed mechanisms have been remained obscure. In this study, the apoptotic and anti-metastatic effects of methylselenol were investigated. The effect of methylselenol generated from selenomethionine (SeMet) with methioninase (METase) on cell proliferation, adhesion, and integrin expression were examined in murine melanoma B16F10 cells, which are highly metastatic to the lungs of syngeneic C57BL/6J mice. Combined treatment with SeMet-METase decreased the expression of integrins $\alpha _4$, $\beta _1$, $\alpha _v$ and $\beta _3$ and inhibited melanoma-ECM adhesion. Caspase-mediated apoptosis was induced following loss of cell adherence. Phosphorylation of focal adhesion kinase (FAK) and Akt, related to integrin-mediated survival, were decreased upon treatment with SeMet-METase while phosphorylation of p38, $PKC-\delta$, and $I\kappaB\alpha$ increased. In the presence of specific inhibitors of p38, $PKC-\delta$, and $NF-\kappa B$, expression of integrins and cell adhesion to ECM were maintained and cell apoptosis was prevented in SeMet-METase-treated melanoma cells. Based on these results, it is proposed that combined treatment with SeMet-METase induces caspase-mediated apoptosis in melanoma cells by altering integrin expression and adhesion. Furthermore, activation of p38, $PKC-\delta$, and $NF-\kappa B$ is a prerequisite for the down-regulation of integrin expression, followed by detac...
Advisors
Yoo, Ook-Joonresearcher유욱준researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2007
Identifier
263435/325007  / 020025817
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2007. 2, [ xiv, 125 p. ]

Keywords

셀레늄; metastasis; 흑색종; 인테그린; 세포사멸; 전이; 메틸셀레놀; Selenium; methylselenol; melanoma; integrin; apoptosis

URI
http://hdl.handle.net/10203/27623
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=263435&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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