합성 담즙산 유도체에 의한 세포사멸 및세포주기조절 (Modulation of Apoptosis and Cell Cycle by Synthetic Bile Acid Derivatives)

서지정보

· 발행기관 : 대한해부학회
· 수록지 정보 : Anatomy and Cell Biology / 41권 / 1호 / 1 ~ 11페이지
· 저자명 : 박상은, 임은옥, 최영현, 김남득, 유영현

초록

This paper outlines the current understanding of cell cycle modulation and induction of apoptosis in
cancer cells by natural and synthetic bile acid. Bile acid homeostasis is tightly regulated in health, and the cellular and
tissue concentrations of bile are restricted. However, when pathophysiological processes impair biliary secretion, hepatocytes
are exposed to an elevated concentration of bile acids, which triggers cell death. In this context, we have synthesized
several new bile acid derivatives. These synthetic bile acids modulate the cell cycle and induce apoptosis in
several human cancer cells similar to the effects of natural bile acids. In human breast and prostate cancer cells with
different tumor suppressor p53 status, synthetic bile acid induced growth inhibition and apoptosis, and these changes
were associated with upregulation of Bax and p21WAF1/CIP1 through a p53-independent pathway. In Jurkat human T
cell leukemia cells, the synthetic bile acids induced apoptosis through caspase activation. The synthetic bile acids induced
apoptosis in a JNK-dependent manner in SiHa human cervical cancer cells through the induction of Bax and
activation of caspases in PC3 prostate cancer cells and induction of G1 phase arrest of the cell cycle in HT29 colon
cancer cells. The synthetic bile acids also induced apoptosis in four human glioblastoma multiform cell lines (e.g., U-
118MG, U-87MG, T98G, and U-373MG) and one human TE671 medulloblastoma cell line. A chenodeoxycholic acid
derivative, called HS-1200, significantly decreased the growth of TE671 medulloblastoma tumor size and increased
lifespan in nonobese diabetic and severe combined immunodeficient (NOD/SCID) mice. These findings suggest that
these new synthetic bile acids, which are novel apoptosis mediators, might be applicable to the treatment of various
human cancer cells.

영어초록

This paper outlines the current understanding of cell cycle modulation and induction of apoptosis in
cancer cells by natural and synthetic bile acid. Bile acid homeostasis is tightly regulated in health, and the cellular and
tissue concentrations of bile are restricted. However, when pathophysiological processes impair biliary secretion, hepatocytes
are exposed to an elevated concentration of bile acids, which triggers cell death. In this context, we have synthesized
several new bile acid derivatives. These synthetic bile acids modulate the cell cycle and induce apoptosis in
several human cancer cells similar to the effects of natural bile acids. In human breast and prostate cancer cells with
different tumor suppressor p53 status, synthetic bile acid induced growth inhibition and apoptosis, and these changes
were associated with upregulation of Bax and p21WAF1/CIP1 through a p53-independent pathway. In Jurkat human T
cell leukemia cells, the synthetic bile acids induced apoptosis through caspase activation. The synthetic bile acids induced
apoptosis in a JNK-dependent manner in SiHa human cervical cancer cells through the induction of Bax and
activation of caspases in PC3 prostate cancer cells and induction of G1 phase arrest of the cell cycle in HT29 colon
cancer cells. The synthetic bile acids also induced apoptosis in four human glioblastoma multiform cell lines (e.g., U-
118MG, U-87MG, T98G, and U-373MG) and one human TE671 medulloblastoma cell line. A chenodeoxycholic acid
derivative, called HS-1200, significantly decreased the growth of TE671 medulloblastoma tumor size and increased
lifespan in nonobese diabetic and severe combined immunodeficient (NOD/SCID) mice. These findings suggest that
these new synthetic bile acids, which are novel apoptosis mediators, might be applicable to the treatment of various
human cancer cells.

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