Antitumor Effects of Droloxifene, a New Antiestrogen Drug, against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats

Kawamura, Ikuo; Mizota, Tamotsu; Kondo, Naomi; Shimomura, Kyoichi; Kohsaka, Masanobu

doi:10.1254/jjp.57.215

Cited by 24 publications

(5 citation statements)

References 31 publications

(35 reference statements)

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“…Prior to its use, DMBA was dissolved in sesame oil at 120˚C (DMBA 1,000 mg/50 ml sesame oil). A single dose of 80 mg/kg body weight was administered orally (17). The same amount of sesame oil without DMBA was administered to the animals in the CTR group.…”

Section: Dietmentioning

confidence: 99%

Dietary effect of mead acid on DMBA‑induced breast cancer in female Sprague‑Dawley rats

et al. 2020

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In the present study, the dietary effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in female Sprague-Dawley rats were examined. The 2.4 and 4.8% MA diets were commenced when the rats were 6 weeks of age. DMBA was administered by a single oral ingestion when the rats were 7 weeks of age, and the rats were maintained on the respective diets until 19 weeks of age. Tumor weight, histopathology, cell kinetics, and the fatty acid composition in breast tissue and serum were examined. In the control (CTR) group, the DMBA-exposed rats were fed a basal diet (0% MA). The results revealed that there were no significant differences in tumor incidence, cell kinetics and in the N-6/N-3 ratio in breast tissue between the groups. Only the N-6/N-3 ratio of fatty acid composition in serum was significantly decreased in the 2.4% MA diet group. In previous studies, the 2.4% MA diet was shown to suppress N-methyl-N-nitrosourea-induced luminal A mammary cancer by decreasing cancer cell proliferation. The findings of the present study differ from those of previous studies with different breast cancer models. To further clarify the effects of MA against breast carcinogenesis, further investigations with different experimental breast cancer models are recommended.

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Section: Dietmentioning

confidence: 99%

Dietary effect of mead acid on DMBA‑induced breast cancer in female Sprague‑Dawley rats

et al. 2020

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“…Because antiestrogens (230,(275)(276)(277)(278) as well as DHEA (258) can independently inhibit the development of DMBAinduced mammary carcinoma, we have studied the potential benefits of combining the new antiestrogen EM-800 with DHEA on the development of mammary carcinoma induced by DMBA in the rat. As illustrated in Fig.…”

Section: Additive Inhibitory Effects Of Dhea and The Antiestrogen mentioning

confidence: 99%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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Serum androgens as well as their precursors and metabolites decrease from the age of 30-40 yr in women, thus suggesting that a more physiological hormone replacement therapy at menopause should contain an androgenic compound. It is important to consider, however, that most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) of adrenal origin. Much progress in this new area of endocrine physiology called intracrinology has followed the cloning and characterization of most of the enzymes responsible for the transformation of DHEA and DHEA-S into androgens and estrogens in peripheral target tissues, where the locally produced sex steroids are exerting their action in the same cells in which their synthesis takes place without significant diffusion into the circulation, thus seriously limiting the interpretation of serum levels of active sex steroids. The sex steroids made in peripheral tissues are then inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured. In a series of animal models, androgens and DHEA have been found to inhibit breast cancer development and growth and to stimulate bone formation. In clinical studies, DHEA has been found to increase bone mineral density and to stimulate vaginal maturation without affecting the endometrium, while improving well-being and libido with no significant side effects. The advantage of DHEA over other androgenic compounds is that DHEA, at physiological doses, is converted into androgens and/or estrogens only in the specific intracrine target tissues that possess the appropriate physiological enzymatic machinery, thus limiting the action of the sex steroids to those tissues possessing the tissue-specific profile of expression of the genes responsible for their formation, while leaving the other tissues unaffected and thus minimizing the potential side effects observed with androgens or estrogens administered systemically.

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“…α-Hydroxytamoxifen (α-OHTAM) and 4-hydroxytamoxifen (4-OHTAM) are metabolites capable of forming DNA adducts through a secondary metabolism involving the oxidation of 4-hydroxytamoxifen (4-OHT) to quinone methide (Scheme 1) [156][157][158][159]. N-desmethyl-tamoxifen, although less potent than 4-OHT, is the principal metabolite with a comparable binding affinity to that of tamoxifen [160]. 4-OHT has 20-30 fold more binding affinity for the ER than that of tamoxifen, thus with similar affinity as estradiol [161][162][163][164][165][166], accounting for the antiestrogen activity of tamoxifen [167].…”

Section: Tamoxifenmentioning

confidence: 99%

Medicinal Chemistry and Emerging Strategies Applied to the Development of Selective Estrogen Receptor Modulators (SERMs)

Musa¹,

Khan²,

Cooperwood³

2007

CMC

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Selective estrogen receptor modulators (SERMs), known previously as "antiestrogens", are a new category of therapeutic agents used for the prevention and treatment of diseases such as osteoporosis and breast cancer. SERMs act as ER-agonist in some tissues while acting as ER-antagonist in others based on conformational change of the receptors, particularly at the helix 12. Currently, there are two classes of clinically approved SERMs; triphenylethylene derivatives (e.g., tamoxifen) and benzothiophene derivatives (e.g., raloxifene). Tamoxifen, raloxifene and toremifene are the most widely used SERMs. Tamoxifen, an antagonist of the breast tissue, is the first clinically identified compound with noticeable SERM activity. Although tamoxifen has been very successful in breast cancer treatment, its agonistic effect on the uterus is said to be associated with increase risk of developing endometrial cancer. Ideally, it is presumed that SERMs should selectively act as an agonist in the bone and brain while simultaneously acting as an antagonist in the breast and uterus. Therefore, the therapeutic goal of SERMs is the prevention of estrogen deficiency diseases without promoting estrogen-associated tumor growth. Therefore, the objective of this review is to summarize various effects that have been applied in improving the tissue-selectivity of SERMs, highlighting the emerging understanding of their mechanism of actions in selected target tissues and the development of the SERMs. The significance in recent discovery of selective estrogen receptor alpha modulators, SERAMs will also be reviewed.

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Antitumor Effects of Droloxifene, a New Antiestrogen Drug, against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats

Cited by 24 publications

References 31 publications

Dietary effect of mead acid on DMBA‑induced breast cancer in female Sprague‑Dawley rats

Dietary effect of mead acid on DMBA‑induced breast cancer in female Sprague‑Dawley rats

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Medicinal Chemistry and Emerging Strategies Applied to the Development of Selective Estrogen Receptor Modulators (SERMs)

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