From: CYMM (cymm@trinidad.net)
Date: Fri Dec 01 2000 - 09:58:42 MST
Hi Extropians,
I'm still interested in the exact reasons why lapachone & taxol combos would
wake up defective checkpoints....
(Such a regime might have cancer prophylaxis worth for life
extensionists...)
This paper (abstract below) seems to offer an explanation of sorts.
cymm
**************************************
Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol:
combining drugs imposes different artificial checkpoints.
Li CJ, Li YZ, Pinto AV, Pardee AB
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute,
Department of Biological Chemistry, Harvard Medical School, 44 Binney
Street, Boston, MA 02115, USA. cjli@mbcrr.harvard.edu
Ablation of tumor colonies was seen in a wide spectrum of human carcinoma
cells in culture after treatment with the combination of beta-lapachone and
taxol, two low molecular mass compounds. They synergistically induced death
of cultured ovarian, breast, prostate, melanoma, lung, colon, and pancreatic
cancer cells. This synergism is schedule dependent; namely, taxol must be
added either simultaneously or after beta-lapachone. This combination
therapy has unusually potent antitumor activity against human ovarian and
prostate tumor prexenografted in mice. There is little host toxicity. Cells
can commit to apoptosis at cell-cycle checkpoints, a mechanism that
eliminates defective cells to ensure the integrity of the genome. We
hypothesize that when cells are treated simultaneously with drugs activating
more than one different cell-cycle checkpoint, the production of conflicting
regulatory signaling molecules induces apoptosis in cancer cells.
beta-Lapachone causes cell-cycle delays in late G(1) and S phase, and taxol
arrests cells at G(2)/M. Cells treated with both drugs were delayed at
multiple checkpoints before committing to apoptosis. Our findings suggest an
avenue for developing anticancer therapy by exploiting apoptosis-prone
"collisions" at cell-cycle checkpoints.
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