Positional isomers of acetaminophen differentially induce proliferation of cultured breast cancer cells

Harnagea-Theophilus, Eugenia; Miller, Michael R.; Rao, N.A.

doi:10.1016/s0378-4274(98)00227-6

Cited by 8 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies demonstrate that APAP has estrogen-like activity in breast cancer cell proliferation studies (Harnagea-Theophilus et al, 1998) and inhibits estrogen-induced vitellogenin production in isolated trout liver cells (Miller et al, 1999). No appreciable interactions between APAP and the estrogen receptor have been found (Harnagea-Theophilus b et al, 1999, Isenhower et al, 1986 and the mechanism by which APAP alters these estrogenic-responses is unclear. In addition, case studies indicate an association between APAP and lowered risk of ovarian cancer and altered basal hormone levels, including estrogen, in women who take the drug (Cramer a , b et al, 1998).…”

Section: Hypothesismentioning

confidence: 99%

“…In vitro studies have shown that acetaminophen has the ability to induce estrogen-mediated DNA synthesis and cell proliferation in estrogen receptor positive (ER+) breast cancers cells (Harnagea-Theophilus et al, 1998) and inhibits estradiol-induced vitellogenin production in trout liver cells . Although no estrogenic activity was observed in uterotropic bioassays (Harnagea-Theophilus b et al, 1999, Isenhower et al, 1986, animal studies have shown that APAP reduced the number of litters per breeding pair, increased abnormal sperm counts and increased testicular atrophy in mice (Boyd et al, 1970, Reel et al, 1992. Even more significant are case studies indicating that APAP has endocrine altering effects in the human population such as lowering basal hormone levels in women (Cramer b et al, 1998) and reducing the risk of ovarian cancer .…”

Section: Introduction Endocrine Disrupters and Acetaminophenmentioning

confidence: 99%

See 1 more Smart Citation

Effects of acetaminophen on estrogen-responsive alkaline phosphatase in Ishikawa endometrial cancer cells

Dowdy¹

View full text Add to dashboard Cite

This study examines the effect of acetaminophen (APAP) on the estrogen-responsive gene alkaline phosphatase in Ishikawa endometrial cancer cells. Basal levels of alkaline phosphatase activity were significantly inhibited in cells treated with 0.03, 0.1, 0.3 and 1mM APAP compared to control. Alkaline phosphatase activity induced with 1nM estradiol was significantly inhibited in a concentration dependent manner by 0.0.1, 0.3 and 1mM APAP. APAP did not directly inhibit the activity of alkaline phosphatase at any of the concentrations tested. Increasing estradiol concentrations (0.01, 0.1 and 1nM) did not alter the level of inhibition of alkaline phosphatase activity by 0.1, 0.3 or 1mM APAP. This is in agreement with other studies, which have concluded that APAP does not compete with estradiol for binding at the estrogen receptor (Harnagea-Theophilus a et al., 1999; Isenhower et al., 1986; Miller et al., 1999). Protein concentrations were significantly decreased in Ishikawa cells with 0.3 and 1mM APAP alone or in the presence of 0.01, 0.1 to 1nM estradiol. Inhibition of alkaline phosphatase activity by high levels (0.3 and 1mM) of APAP may be in part due to toxic effects of APAP as determined by LDH release. Fluorescent microscopy using calcein staining techniques show that Ishikawa cells treated with 1nM E2+0.3mM APAP are visibility misshapen; cells treated with 1nM E2+1mM APAP are no longer attached to the plate indicating toxicity. The final part of this study looked at the interaction between antiestrogen-4-hydroxy tamoxifen (OHT) and APAP on alkaline phosphatase activity in Ishikawa cells. While OHT inhibited alkaline phosphatase activity ~50 percent in estradiol-induced cells, addition of 0.03-1mM APAP increased inhibition significantly in a concentration dependent manner. Results of this study indicate that APAP decreases estrogen-responsive alkaline phosphatase activity in Ishikawa cells in vitro, and that this inhibition is not attributed to direct inhibition of enzyme activity.

show abstract

Section: Hypothesismentioning

confidence: 99%