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The effect of estramustine on microtubuli is different from the direct action via oxygen radicals on DNA and cell membrane

Henriksson, R; Bjermer, Leif LU ; Von Schoultz, E and Grankvist, K (1990) In Anticancer Research 10(2A). p.303-309
Abstract
Estramustine (EM), a complex between estradiol-17 beta and nornitrogen mustard, is commonly used in the treatment of prostatic cancer. The exact mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically with the mitotic spindle, and to be related to the intact EM complex. In the present study, using different cell-systems (monocyte phagocytosis transformed fibroblasts, colon cancer cells), the EM cytotoxicity was also found to involve direct interaxtion with DNA and cell membranes. The interaction with DNA was shown by a DNA precipitation assay using 3H- and 14C- thymidine, and the cell membrane damage by using 86Rb- accumulation as a sensitive marker for active potassium uptake.... (More)
Estramustine (EM), a complex between estradiol-17 beta and nornitrogen mustard, is commonly used in the treatment of prostatic cancer. The exact mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically with the mitotic spindle, and to be related to the intact EM complex. In the present study, using different cell-systems (monocyte phagocytosis transformed fibroblasts, colon cancer cells), the EM cytotoxicity was also found to involve direct interaxtion with DNA and cell membranes. The interaction with DNA was shown by a DNA precipitation assay using 3H- and 14C- thymidine, and the cell membrane damage by using 86Rb- accumulation as a sensitive marker for active potassium uptake. EM effects in the fibroblasts were inhibited by various metal chelators and radical scavengers. Involvement of free oxygen radicals was further indicated in a cell-free system with an oxygen electrode. The EM inhibition of monocyte phagocytosis was related to the engulfment, and was not at all influenced by radical scavengers. In contrast to EM, neither of its components alone, or together, affected monocyte engulfment. Finally, it was shown that the colon cancer cell-line HT-29 was resistant to both of the two suggested and separate mechanisms for EM toxicity: an interaction with the microtubuli system by the intact EM complex and a more unspecific action mediated by free-oxygen radicals. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Anticancer Research
volume
10
issue
2A
pages
303 - 309
publisher
International Institute of Cancer Research
external identifiers
  • pmid:2346305
  • scopus:0025279714
ISSN
1791-7530
language
English
LU publication?
no
id
0e7c661a-3fa1-4afa-8471-cf36c961800b (old id 1105050)
date added to LUP
2008-08-04 15:54:27
date last changed
2017-07-30 03:31:33
@article{0e7c661a-3fa1-4afa-8471-cf36c961800b,
  abstract     = {Estramustine (EM), a complex between estradiol-17 beta and nornitrogen mustard, is commonly used in the treatment of prostatic cancer. The exact mechanism of action is unknown but has previously been considered to be mediated through non-DNA targets, specifically with the mitotic spindle, and to be related to the intact EM complex. In the present study, using different cell-systems (monocyte phagocytosis transformed fibroblasts, colon cancer cells), the EM cytotoxicity was also found to involve direct interaxtion with DNA and cell membranes. The interaction with DNA was shown by a DNA precipitation assay using 3H- and 14C- thymidine, and the cell membrane damage by using 86Rb- accumulation as a sensitive marker for active potassium uptake. EM effects in the fibroblasts were inhibited by various metal chelators and radical scavengers. Involvement of free oxygen radicals was further indicated in a cell-free system with an oxygen electrode. The EM inhibition of monocyte phagocytosis was related to the engulfment, and was not at all influenced by radical scavengers. In contrast to EM, neither of its components alone, or together, affected monocyte engulfment. Finally, it was shown that the colon cancer cell-line HT-29 was resistant to both of the two suggested and separate mechanisms for EM toxicity: an interaction with the microtubuli system by the intact EM complex and a more unspecific action mediated by free-oxygen radicals.},
  author       = {Henriksson, R and Bjermer, Leif and Von Schoultz, E and Grankvist, K},
  issn         = {1791-7530},
  language     = {eng},
  number       = {2A},
  pages        = {303--309},
  publisher    = {International Institute of Cancer Research},
  series       = {Anticancer Research},
  title        = {The effect of estramustine on microtubuli is different from the direct action via oxygen radicals on DNA and cell membrane},
  volume       = {10},
  year         = {1990},
}