Document Detail


Modulation of the cell cycle and induction of apoptosis in human cancer cells by synthetic bile acids.
MedLine Citation:
PMID:  17168673     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this paper, we will outline 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 their cellular and tissue concentrations are restricted. However, when pathophysiological processes impair their biliary secretion, hepatocytes are exposed to elevated concentrations of bile acids which trigger cell death. In this context, we developed several newly synthesized bile acid derivatives. These synthetic bile acids modulated the cell cycle and induced apoptosis in several human cancer cells similar to natural bile acids. In human breast and prostate cancer cells with different tumor suppressor p53 status, synthetic bile acid-induced growth inhibition and apoptosis were associated with up-regulation of Bax and p21(WAF1/CIP1) via a p53-independent pathway. In Jurkat human T cell leukemia cells, the synthetic bile acids induced apoptosis through caspase activation. In addition to this, the synthetic bile acids induced apoptosis in a JNK dependent manner in SiHa human cervical cancer cells, via induction of Bax and activation of caspases in PC3 prostate cancer cells and induction of G1 phase arrest in the cell cycle in HT29 colon cancer cells. Moreover, they induced apoptosis in four human glioblastoma multiform cell lines (i.e., U-118MG, U-87MG, T98G, and U-373MG) and one human TE671 medulloblastoma cells. In addition to this, a chenodeoxycholic acid derivative, called HS-1200, significantly decreased the growth of TE671 medulloblastoma tumor size and increased life span in non-obese diabetic and severe combined immunodeficient (NOD/SCID) mice. Therefore, these new synthetic bile acids, which are novel apoptosis mediators, might be applicable to the treatment of various human cancer cells.
Authors:
Nam Deuk Kim; Eunok Im; Young Hyun Yoo; Yung Hyun Choi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current cancer drug targets     Volume:  6     ISSN:  1873-5576     ISO Abbreviation:  Curr Cancer Drug Targets     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-15     Completed Date:  2007-01-08     Revised Date:  2008-09-09    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  681-9     Citation Subset:  IM    
Affiliation:
Division of Pharmacy (Brain Korea 21 Program), Pusan National University, Research Institute for Drug Development, Busan 609-735, South Korea. nadkim@pusan.ac.kr
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Bile Acids and Salts / pharmacology,  therapeutic use*
Cell Cycle / drug effects*
Humans
Mitochondria / drug effects,  physiology
Neoplasms / drug therapy*,  pathology
Chemical
Reg. No./Substance:
0/Bile Acids and Salts

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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