Plastics substitute may increase breast cancer aggressiveness

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Bisphenol S (BPS), a substitute for the chemical bisphenol A (BPA) in the plastic industry, shows the potential for increasing the aggressiveness of breast cancer through its behaviour as an endocrine-disrupting chemical, an Oakland University study finds.

The results, which tested BPS in human breast cancer cells, were presented at ENDO 2017, The Endocrine Society’s 99th annual meeting in Orlando.

BPS is found in polycarbonate hard plastics, currency bills and thermal paper receipts as well as many products touted to be free of BPA, a known endocrine-disrupting chemical suspected of having multiple possible health risks.

“Despite hopes for a safer alternative to BPA, studies have shown BPS to exhibit similar estrogen-mimicking behavior to BPA,” said the study’s principal investigator, Dr Sumi Dinda, associate professor at Oakland University School of Health Sciences, Rochester, Michigan. Their study confirmed that BPS acts like oestrogen in breast cancer cells, Dinda said, adding, “So far, BPS seems to be a potent endocrine disruptor.”

He and his colleagues studied the effects of BPS on oestrogen receptor-alpha and the BRCA1 gene. Most breast cancers are oestrogen receptor positive, and, according to the National Cancer Institute, 55% to 65% of women who inherit a harmful mutation in the BRCA1 gene will develop breast cancer.

Using two commercially available breast cancer cell lines obtained from women with oestrogen-receptor-positive breast cancer, the research team exposed the cancer cells to varying strengths of BPS or to an inactive substance as a control. The investigators also treated the breast cancer cells with oestradiol (estrogen) and found that BPS acted like oestrogen in multiplying breast cancer cells, Dinda said. Compared with the control, BPS heightened the protein expression in estrogen receptor and BRCA1 after 24 hours, as did oestrogen. After a six-day treatment with BPS, the breast cancer cells in both cell lines reportedly increased in number by 12% at the lowest dose (4 micromolars) and by 60% at 8 micromolars.

The research team then blocked the BPS-induced proliferation of breast cancer cells by treating the cells with anti-oestrogen drugs, which are used to block oestrogen’s action onto oestrogen binding proteins (oestrogen receptors) in breast cancer cells.

Dinda said their findings suggest that BPS may cause breast cancer to become more aggressive. Although further study of BPS in breast cancer cells is needed for confirmation, he suggested that “if a woman has a mutated BRAC1 gene and uses products containing BPS, her risk for developing breast cancer may increase further.”

Abstract
Bisphenol-S (BPS), a substitute for bisphenol-A (BPA), has been suggested to be an endocrine disrupting compound interfering with normal hormonal activity. This bisphenol analogue is found in plastic substitutes, paper currency, and most products marked “BPA-free.” Despite hopes for a safer alternative, studies have shown BPS to exhibit similar estrogenic activity due to its structural commonalities with its analogue BPA. Generally, bisphenols have been shown to disrupt proper estrogen receptor alpha (ERα) functioning in breast cancer cells. Given that a mutated BRCA1 gene will likely develop into hereditary breast cancer in 55-65% of people, determining the estrogenic effects of BPS in both genes is essential. This study focused on the effects of BPS, alone and in combination with hormones and anti-hormones, to examine the expression of ERα and BRCA1 in T-47D and MCF-7 breast cancer cells via Western Blot analyses, cellular viability, and RT-qPCR analyses. Western blot analysis revealed alterations in the expression of ERα and BRCA1 protein levels after 24 hours of treatment with varying concentrations of BPS (4-20 µM). A concentration-dependent decrease of ERα protein levels was observed in both cell lines, with a 49% reduction occurring with 8 µM BPS as compared to control. BRCA1 levels portray continued expression through concentrations of 20 µM BPS, found similarly in both cell lines. To gain further insight into possible similarities between BPS and other known effectors of ERα, the optimal concentration of BPS (8 μM) was used in combination with hormones and anti-hormones. Down-regulation of ERα protein levels was observed after 24-hour co-treatment of T-47D and MCF-7 cells with 8µM BPS and 10 nM E2. BPS with ICI showed significant down-regulation as compared to BPS alone, and BPS with TAM portrayed no significant differences. A similar trend in the effects on BRCA1 expression was depicted in T-47D and MCF-7 cells. Image cytometric analysis with propidium iodide staining was utilized to quantify cell values and viability changes to further portray the effects of BPS on T-47D and MCF-7 cellular growth. Following a six-day treatment with 4 µM to 20 µM BPS, cellular proliferation showed a 12-60% increase in both cell lines. The proliferative effect of E2 and BPS in cells was reversed when treated in combination with anti-estrogens. Gene analysis showed a transcriptional expression of ESR1 mRNA levels that correlate with the translational data obtained via western blot analyses on BPS. This study may contribute to the understanding of the molecular effects in breast cancer cells exhibited by endocrine disrupting compounds, specifically BPS, on tumor suppressor proteins and steroid receptors.

Authors
Katie Marie Aleck, Kelly Marie Hallman, Brigitte Dwyer, Victoria Lloyd, Monica Szmyd, Tyler Bedgood, Ann Fuelle and Sumi Dinda

The Endocrine Society material
ENDO 2017 abstract


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