Cancer development and ageing are complex sciences. From the study on the process of rodent
carcinogenesis, we identified
tumor necrosis factor-alpha (
TNF-alpha) as an important mediator of
cancer development. This paper presents three clinical examples of
TNF-alpha up-regulation: by
cord factors of Mycobacterium tuberculosis, such as
trehalose 6-monomycolate, as an activator of
protein kinase C and by a
cord factor like fraction of Microsporum canis obtained in the air inside houses in Thailand, both of which are risk factors in human
lung cancer development, and by Helicobacter pylori gene product, H. pylori
membrane protein 1 (HP-MP1) in relation to human
stomach cancer. The second part of this paper deals with down-regulation of
TNF-alpha by a wide variety of
cancer preventive agents. Among the various agents, (-)-
epigallocatechin gallate (EGCG) and
green tea polyphenols inhibited
TNF-alpha gene expression in the cells induced by
tumor promoter, mediated through inhibition of
NF-kappaB activation. Studying growth inhibition of human
cancer cell lines by
morphine, we found that
morphine and the new
morphine derivatives KT-90 and KT-87 have anticancer activity mediated through induction of apoptosis, in addition to
analgesic action. We conclude that environmental and endogenous factors induce
NF-kappaB activation mediated through expression of inflammatory
cytokine genes, such as
TNF-alpha, and that the expression pattern of the genes operates similarly in the aging process.