Actions of Estrogenic Endocrine Disrupting Chemicals on Human Prostate Stem/Progenitor Cells and Prostate Carcinogenesis

Abstract

Substantial evidences from epidemiological and animal-based studies indicate that early exposure to endocrine disrupting chemicals (EDCs) during the developmental stage results in a variety of disorders including cancer. Previous studies have demonstrated that early estrogen exposure results in life-long reprogramming of the prostate gland that leads to an increased incidence of prostatic lesions with aging. We have recently documented that bisphenol A (BPA), one of the most studied EDCs with estrogenic activity has similar effects in increasing prostate carcinogenic potential, supporting the connection between EDCs exposure and prostate cancer risk. It is well accepted that stem cells play a crucial role in development and cancer. Accumulating evidence suggest that stem cells are regulated by extrinsic factors and may be the potential target of hormonal carcinogenesis. Estrogenic EDCs which interfere with normal hormonal signaling may perturb prostate stem cell fate by directly reprogramming stem cells or breaking down the stem cell niche. Transformation of stem cells into cancer stem cells may underlie cancer initiation accounting for cancer recurrence, which becomes a critical therapeutic target of cancer management. We therefore propose that estrogenic EDCs may influence the development and progression of prostate cancer through reprogramming and transforming the prostate stem and early stage progenitor cells. In this review, we summarize our current studies and have updated recent advances highlighting estrogenic EDCs on prostate carcinogenesis by possible targeting prostate stem/progenitor cells. Using novel stem cell assays we have demonstrated that human prostate stem/progenitor cells express estrogen receptors (ER) and are directly modulated by estrogenic EDCs. Moreover, employing an in vivo humanized chimeric prostate model, we further demonstrated that estrogenic EDCs initiate and promote prostatic carcinogenesis in an androgen-supported environment. These findings support our hypothesis that prostate stem/progenitor cells may be the direct targets of estrogenic EDCs as a consequence of developmental exposure which carry permanent reprogrammed epigenetic and oncogenic events and subsequently deposit into cancer initiation and progression in adulthood.

Organochlorine pesticides application, xenobiotic metabolizing gene polymorphism and incidences of cancers in India: a review

“…1 According to various research, hormonemediated actions of both endogenous and exogenous hormonal drugs enhance the risk of prostate cancer. 2,3 According to Sonnenschein and Soto (1998), endocrine disruptors are exogenous chemicals that imitate hormones and interfere with physiological working of endogenous hormones. They may also operate as tumour promoters.…”

Emerging and eco-friendly approaches for waste management: a book review

“…Chapters 2, 6, and 7 provide an overview of emerging contaminants, like polycyclic aromatic hydrocarbons (PAHs), and endocrine-disrupting chemicals (EDCs); they may cause various adverse impacts such as alter the hormonal balance as well as breeding behavior of living beings, and ultimately liable to developmental deformities in human, animals as well [3]. These chapters also focus on the degradation and detoxification approaches of many other emerging contaminants.…”