Anti-breast cancer potential of SS5020, a novel benzopyran antiestrogen.

Abstract

Treatment with tamoxifen (TAM) increases the risk of developing endometrial cancer in women. The carcinogenic effect is thought to involve initiation and/or promotion resulting from DNA damage induced by TAM as well as its estrogenic action. To minimize this serious side-effect while increasing the anti-breast cancer potential, a new benzopyran antiestrogen, 2E-3-{4-[(7-hydroxy-2-oxo-3-phenyl-2H-chromen-4-yl)-methyl]-phenyl}-acrylic acid (SS5020), was synthesized. Unlike TAM, SS5020 exhibits no genotoxic activity to damage DNA. Furthermore, SS5020 does not present significant uterotrophic potential in rats; in contrast, the structurally related compounds, TAM, toremifene, raloxifene (RAL) and SP500263 all have uterotrophic activity. At the human equivalent molar dose of TAM (0.33 or 1.0 mg/kg), SS5020 had much stronger antitumor potential than those same antiestrogens against 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats. The growth of human MCF-7 breast cancer xenograft implanted into athymic nude mice was also effectively suppressed by SS5020. SS5020, lacking genotoxic and estrogenic actions, could be a safer and stronger antiestrogen alternative to TAM and RAL for breast cancer therapy and prevention.

• Authors: Naomi Suzuki, Xiaoping Liu, Y R Santosh Laxmi, Kanako Okamoto, Hyo Jeong Kim, Guangxiang Zhang, John J Chen, Yoshinori Okamoto, Shinya Shibutani
• Journal: International journal of cancer (Int J Cancer) Vol. 128 Issue 4 Pg. 974-82 (Feb 15 2011) ISSN: 1097-0215 [Electronic] United States
• PMID: 20824696 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 UICC.

Chemical References

• 3-(4-((7-hydroxy-2-oxo-3-phenyl-2H-chromen-4-yl)-methyl)phenyl)acrylic acid
• Carcinogens
• Cinnamates
• DNA Adducts
• Estrogen Receptor Modulators
• Umbelliferones
• Tamoxifen
• 9,10-Dimethyl-1,2-benzanthracene

Topics

• 9,10-Dimethyl-1,2-benzanthracene (toxicity)
• Animals
• Carcinogens (toxicity)
• Cinnamates (chemical synthesis, chemistry, therapeutic use)
• DNA Adducts
• Estrogen Receptor Modulators (chemical synthesis, chemistry, therapeutic use)
• Female
• Humans
• Mammary Neoplasms, Experimental (chemically induced, prevention & control)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplastic Cells, Circulating
• Rats
• Rats, Sprague-Dawley
• Tamoxifen (therapeutic use)
• Umbelliferones (chemical synthesis, chemistry, therapeutic use)