Tumor Promoters - Microcystin-LR, Nodularin and TNF-α and Human Cancer Development

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


Download PDF Flyer




Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.722
5 - Year: 2.849

Tumor Promoters - Microcystin-LR, Nodularin and TNF-α and Human Cancer Development



Anti-Cancer Agents in Medicinal Chemistry, 11(1): 4-18.

Author(s): Hirota Fujiki and Masami Suganuma.

Affiliation: Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.

Abstract

Microcystin-LR and nodularin, along with okadaic acid, are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A). The mechanisms of action of microcystin-LR and nodularin in the liver and that of okadaic acid, a potent tumor promoter on mouse skin, have attracted the attention of the scientists. This paper reviews several topics: new inhibitors of PP1 and PP2A with new chemical structures, structure-function relationships for both receptor binding and inhibition of protein phosphatases, the crystal structure of PP1 or PP2A – toxin complex, induction of gene expression and apoptosis. These subjects were studied by using in vitro and in vivo experimental systems. Two-stage carcinogenesis experiments with microcystin-LR and nodularin for the first time demonstrated that microcystin- LR is a new tumor promoter in rat liver initiated with diethylnitrosamine (DEN), and that nodularin is a potent tumor promoter associated with weak initiating activity in rat liver initiated with DEN. A working group of WHO (IARC) concluded that microcystin-LR is “possibly carcinogenic to humans” and that nodularin is “not classifiable as to carcinogenicity”. Our studies revealed that chemical tumor promoters are inducers of TNF-α in the cells of target tissues and that TNF-α is an endogenous tumor promoter. This advance in carcinogenesis made it possible to look for the link between chemical tumor promoters and endogenous tumor promoters, such as TNF-α and IL-1. The carcinogenic features of TNF-α are described in this review, and the TNF-α inducing protein (Tipα) of elicobacter pylori genome is presented as an example of a tumor promoter of human stomach cancer development.

Keywords:

Apparent activation of protein kinases, microcystin-LR, nodularin, liver carcinogenesis, okadaic acid, protein phosphatases 1 and 2A, tumor necrosis factor, tumor promotion, IARC, TNF, DEN.



Download Free Order Reprints Order Eprints Rights and Permissions




Article Details

Volume: 11
Issue Number: 1
First Page: 4
Last Page: 18
Page Count: 15
DOI: 10.2174/187152011794941163
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2016 Bentham Science