John Murphy, MDLinx | April 09, 2017
More than a decade ago, researchers suggested a link between the compound bisphenol-A (BPA) and adverse health effects, including cancer. BPA was, and still is, widely used to manufacture clear and shatterproof polycarbonate plastic products, such as water bottles, CDs, DVDs, and the lining of food and soda cans.
By 2009, after researchers and consumers increased their concerns about BPA’s safety, most commercial manufacturers in the United States voluntarily stopped using the compound to make baby bottles and sippy cups.
Soon afterward, many companies promoted their products as “BPA-free.” Some plastics manufacturers had turned to a common cousin of BPA, bisphenol-S (BPS), which has a similar structure and is used in many of the same everyday products, including paper money and cash register receipts.
But now investigators suspect that BPS also may be related to adverse health effects, and that products touted as “BPA-free” may not be any safer. A study presented at ENDO 2017, the Endocrine Society’s annual meeting, investigated the effect that BPS may have on breast cancer.
In this interview, lead author Sumit Dinda, PhD, of Oakland University in Rochester, MI, discusses the results and implications of the study.
MDLinx: What did your study investigate, and what did you conclude?
Dr. Dinda: Our study focused on the estrogen-like effects of BPS, alone and in combination with hormones and anti-hormones, on breast cancer cells.
BPS has been suggested to be an endocrine-disrupting compound that interferes with the normal hormonal activity in the body. This could have far-reaching implications because the use of this bisphenol analogue is widespread. BPS is found in plastic substitutes, paper currency, and most products marked “BPA-free.” The potency of the endocrine-disrupting abilities of BPS, compared with BPA, could show whether BPS is, or is not, a suitable alternative to BPA in many everyday products.
Bisphenols specifically affect the proper functioning of estrogen receptors, such as estrogen receptor alpha (ERα), which disrupts the normal activity of the hormone estrogen. Studies suggest BPS affects ERα pathways via its estrogen-mimicking properties in the body, causing increased cell proliferation and resulting in increased breast cancer risk. Despite the hope of a safer substitute, studies have shown that BPS exhibits similar estrogenic activity compared with its analogue BPA, due to their structural commonalities.
We also wanted to know the effect of BPS on BRCA1. Given that a mutated BRCA1 gene will likely develop into hereditary breast cancer in 55% to 65% of people, it is also important to study the effects of BPS on the expression of this protein.
For our study, we exposed two cancer cell lines to various concentrations of BPS, from 4 µM to 20 µM. After 24 hours of BPS exposure to the cancer cells, Western blot analysis revealed alterations in the expression of ERα and BRCA1 protein levels. In both cell lines, we observed a concentration-dependent decrease of ERα protein levels. Also in both cell lines, expression of BRCA1 protein levels continued up to the highest concentrations of BPS.
After a six-day treatment with the same range of BPS concentrations, both cell lines showed a 12% to 60% increase in cellular proliferation. But when we treated the cancer cells in combination with anti-estrogens, the proliferative effect of estradiol and BPS in cells was reversed.
Our results show that BPS displays estrogen-like behavior in breast cancer cells, suggesting it may not be a safer BPA alternative.
MDLinx: Your investigation used concentrations of BPS between 4 µM and 20 µM on breast cancer cells. How do those concentrations compare with a woman’s “regular exposure” to BPS?
Dr. Dinda: Current research lacks the data regarding the actual exposure concentration of BPS in women. Investigators in obesity research have used concentrations of 25 µM and higher in their cell lines. Studies have also found that people in New York are exposed to an estimated 31 µg per day of BPS.
We selected our concentration range based on the current in vitro studies in different cell systems, and we found that BPS shows optimal effects at a concentration of 8 µM.
MDLinx: What implications does your study have for women (especially those susceptible to breast cancer) and their exposure to BPS?
Dr. Dinda: In our study, BPS treatment was comparable to estrogen treatment in ERα and BRCA1 expression in cancer cells. BPS treatment increased breast cancer cell growth, while anti-estrogens blocked the estrogenic-like effects of BPS. So, the results of this study may contribute to the understanding of the relationship between ERα, BRCA1 expression, and bisphenol-S in breast cancer treatment and prevention.
MDLinx: In regard to BPS and BPA exposure, what might you advise oncologists to consider in their patients who have estrogen-receptor-positive breast cancer?
Dr. Dinda: Clinicians, especially those who are dealing with breast cancer patients, should be knowledgeable about the potential health risk of BPS. Due to the interaction of BPS with estrogen receptor and BRCA1 genes, this may cause the cancer to become aggressive.
MDLinx: What research will you conduct to follow up on this investigation?
Dr. Dinda: Further studies of the effects of BPS on breast cancer cells are currently underway in our laboratory.
About Dr. Dinda: Sumit Dinda, PhD, is Associate Professor of Biomedical Diagnostic and Therapeutic Sciences at Oakland University’s School of Health Sciences in Rochester, MI.