Exposure to Bisphenol A Correlates with Early-Onset Prostate Cancer and Promotes Centrosome Amplification and Anchorage-Independent Growth In Vitro

Pheruza Tarapore,Shuk-Mei Ho,Jun Ying,Bruce Bracken,Barbara Burke,Bin Ouyang,Natasha Kyprianou

doi:10.1371/journal.pone.0090332

Pheruza Tarapore, Shuk-Mei Ho + Show 5 more

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https://doi.org/10.1371/journal.pone.0090332

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Journal: PloS one	Publication Date: Mar 3, 2014
Citations: 99	License type: CC BY 4.0

Affiliation: University of Cincinnati Medical Center

Abstract

Human exposure to bisphenol A (BPA) is ubiquitous. Animal studies found that BPA contributes to development of prostate cancer, but human data are scarce. Our study examined the association between urinary BPA levels and Prostate cancer and assessed the effects of BPA on induction of centrosome abnormalities as an underlying mechanism promoting prostate carcinogenesis. The study, involving 60 urology patients, found higher levels of urinary BPA (creatinine-adjusted) in Prostate cancer patients (5.74 µg/g [95% CI; 2.63, 12.51]) than in non-Prostate cancer patients (1.43 µg/g [95% CI; 0.70, 2.88]) (p = 0.012). The difference was even more significant in patients <65 years old. A trend toward a negative association between urinary BPA and serum PSA was observed in Prostate cancer patients but not in non-Prostate cancer patients. In vitro studies examined centrosomal abnormalities, microtubule nucleation, and anchorage-independent growth in four Prostate cancer cell lines (LNCaP, C4-2, 22Rv1, PC-3) and two immortalized normal prostate epithelial cell lines (NPrEC and RWPE-1). Exposure to low doses (0.01–100 nM) of BPA increased the percentage of cells with centrosome amplification two- to eight-fold. Dose responses either peaked or reached the plateaus with 0.1 nM BPA exposure. This low dose also promoted microtubule nucleation and regrowth at centrosomes in RWPE-1 and enhanced anchorage-independent growth in C4-2. These findings suggest that urinary BPA level is an independent prognostic marker in Prostate cancer and that BPA exposure may lower serum PSA levels in Prostate cancer patients. Moreover, disruption of the centrosome duplication cycle by low-dose BPA may contribute to neoplastic transformation of the prostate.

Highlights

Prostate cancer (PCa) is the second most common malignancy among men in North America
Urinary bisphenol A (BPA) level is associated with PCa and may have prognostic value We studied 60 urology patients, 27 with PCa and 33 without PCa
In the younger patients (,65 yr), the geometric mean of urinary BPA levels among PCa patients was 8.08 [95% CI; 2.40, 27.15] mg/g vs. a geometric mean of 0.90 [95% CI; 0.36, 2.25] mg/g among non-PCa patients (p = 0.006; Fig. 1B & 1D)

Summary

Introduction

Prostate cancer (PCa) is the second most common malignancy among men in North America. Aging is a well-established risk factor for PCa [1]. One in six men will develop PCa over their lifetime; the cancer is rarely diagnosed in men ,40 years old, with almost two-thirds cases reported [2], [3] in men at age 65. Major contributing factors other than age are race and family history [1], whereas little is known about the impact of endocrine disruptors on PCa. Bisphenol A (BPA) is an organic compound with the chemical formula (CH3)2C(C6H4OH). In vitro and animal studies have shown that BPA exposure can increase the risk of mammary gland, brain, and prostate cancers [9]. Human studies linking BPA exposure to heightened cancer risk are scarce. One such study in China showed that the incidence of meningioma was 1.6 times higher in adults with higher concentrations of BPA in urine than in those with lower

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