Abstract
Estrogen receptor antagonists are effective in breast cancer treatment. However, the side effects of these treatments have led to a rise in searching for alternative therapies. The present study evaluated the estrogenic, antiestrogenic, and antiproliferative activities of Euphorbia bicolor (Euphorbiaceae), a plant native to south-central USA. Estrogenic and antiestrogenic activities of latex extract and its phytochemicals were evaluated with a steroid-regulated yeast system expressing the human estrogen receptor α and antiproliferative properties were assessed in the ER-positive MCF-7 and T47-D and triple-negative MDA-MB-231 and MDA-MB-469 breast carcinomas. Genistein and coumestrol identified in the latex extract induced higher estrogenic and antiestrogenic activities compared to diterpenes and flavonoids. The latex extract, resiniferatoxin (RTX) and rutin induced antiproliferative activities in all cell lines in a dose-dependent manner, but not in human normal primary dermal fibroblast cultures. A biphasic effect was observed with MDA-MB-468 breast carcinoma in which the latex extract at low concentrations increased and at high concentrations decreased cell proliferation. Treatments with latex extract in combination with RTX or rutin reduced even more the proliferation of MCF-7 breast carcinoma compared to the individual latex, RTX, and rutin treatments. E. bicolor latex phytochemicals could contribute to developing commercial therapeutic agents for breast cancer treatment.
Highlights
Breast cancer is one of the most frequently diagnosed cancers in women
Estrogen receptor alpha especially is an important target for drug development for the prevention and treatment of breast cancer [4] and estrogen receptor positive (ER+) tumors show relatively better prognoses for treating breast cancer as compared to ER-negative breast cancer, especially the triple negative breast cancer, which does not express the hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR) [5]
We report that the E. bicolor latex extract and its phytochemicals induced estrogenic and antiestrogenic properties in a steroid-regulated yeast system and possessed antiproliferative properties in ER-positive MCF-7 and T47-D and triple negative MDA-MB-231 and MDA-MB-469 breast carcinomas without affecting the growth of the human normal primary dermal fibroblast cell line
Summary
Breast cancer is one of the most frequently diagnosed cancers in women. In 2018, 25.4% of the total number of new cases diagnosed were breast cancer [1]. 268,600 (15.2%) new cases of breast cancer have been estimated so far in 2019 [2]. Present in approximately 75% of breast cancers, are known to play important roles in the initiation and progression of breast cancer ([3]; and references within). Estrogen receptor alpha especially is an important target for drug development for the prevention and treatment of breast cancer [4] and estrogen receptor positive (ER+) tumors show relatively better prognoses for treating breast cancer as compared to ER-negative breast cancer, especially the triple negative breast cancer, which does not express the hormone epidermal growth factor receptor 2 (HER-2), estrogen receptors (ER), and progesterone receptors (PR) [5].
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