Re: MOLBIO: insignts into cancer

From: Robert J. Bradbury (
Date: Sun Oct 08 2000 - 15:08:58 MDT

cymm wrote:
> While you're into oncology... please try to find other definitive
> leads demonstrating why topoisomerase inhibitors (eg, beta-lapachone;
> cucurmin..) seem to drastically reduce carcinogenesis.

I bet they don't reduce initiation, but the probably slow down the
rapid division of cancerous cells. If I recall correctly, topisomerases
are essential for DNA replication and perhaps RNA transcription. They
are required to fix the degree of DNA supercoiling that occurs during
those processes. If they are toxic to the production of RBC and/or
your gut in high doses, then that is definately how they are acting.
There may be some suggestion that some of the compounds in soy act
instead by encouraging cell differentiation.

topisoomerase: one of a group of enzymes that control the topological
state of DNA and catalyze the interconversion of the topological
isomers of DNA. These reactions include changes in superhelicity and
the formation of knotted and catenated structures. All topological
interconversions of DNA require transient breakage and rejoining of
DNA strands. Accordingly, topisomerases are divided into two
groups: Type I enzymes produce a transient break in a single strand
of the duplex, while Type II enzymes produce a transient double-strand
break in the duplex. (hmmmmm, better not let go!!) Some of the Type I
enzymes (oringally named DNA relaxing enzymes, swivelases, untwisting
enzymes, untwistases, or nicking closing enzymes) carry out the relaxation
of superhelical DNA. The Type II enzymes include the DNA gyrases, enzymes
that convert relaxed closed circular DNA to a superhelical form.

Looking at genbank currently, it looks like humans may have, 3 topoisomerases,
the one targeted by the drugs seems to be Topoisomerase II.


Here are some references:

Capranico G, Giaccone G, D'Incalci M.
DNA topoisomerase II poisons and inhibitors.
Cancer Chemother Biol Response Modif. 1999;18:125-43. Review.
No abstract available.
PMID: 10800480; UI: 20260274

Takimoto CH, Kieffer LV, Kieffer ME, Arbuck SG, Wright J.
DNA topoisomerase I poisons.
Cancer Chemother Biol Response Modif. 1999;18:81-124. Review.
No abstract available.
PMID: 10800479; UI: 20260273

Sharma S, Saltz LB.
Oral chemotherapeutic agents for colorectal cancer.
Oncologist. 2000;5(2):99-107. Review.
PMID: 10794800; UI: 20257152

Stevens CW, Lee JS, Cox J, Komaki R.
Novel approaches to locally advanced unresectable non-small cell lung cancer.
Radiother Oncol. 2000 Apr;55(1):11-8. Review.
PMID: 10788683; UI: 20251208

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