Curcumin as an Antidote to Atrazine on Estrogen Homeostasis and Beyond: Mechanistic Insights from a Targeted Literature Review

Patrick J. WrightJade IlaliPengli Bu^*

• St. John's University, Queens, United States

As the most common cancer in women globally, breast cancer poses a significant public health concern. More concerning is its rising incidence rates in certain areas of the world, including Australia, New Zealand, Western Europe, and North America.Exposure to environmental endocrine-disrupting chemicals may play a role. One such chemical is atrazine (ATZ), a man-made herbicide highly prevalent in the environment and detectable in drinking water, with reported levels ranging from 0.026 to 1.29 micrograms per liter (µg/L) in surface waters in the United States. During the development of breast cancer, many factors are involved, in particular the female sex hormone estrogen. Estrogen signaling fuels the proliferation and migration of estrogen receptor (ER)-positive breast cancer. The current review presents multiple lines of qualitative evidence from in vitro, in vivo, and epidemiological studies connecting ATZ exposure to processes important for breast cancer development. Specifically, ATZ's stimulatory effect on breast cancer is mediated, at least partially, through enhanced CYP19A1 activity, the key enzyme converting testosterone to estradiol. ATZ stimulates CYP19A1 activity via parallel pathways, as evidenced by in vitro studies, potentially leading to elevated estradiol levels and estrogen signaling, which would then drive the development of ER-positive breast cancers. Beyond estrogen signaling, ATZ taps into the epidermal growth factor (EGF) signaling pathway to stimulate uncontrolled proliferation in human cell lines. We then show how curcumin, a phytochemical in turmeric, may counteract ATZ's effect on the aforementioned processes. Once curcumin passes through the ADME process and becomes available in the human body, curcumin