Akhilesh Prajapati

Prostate cancer (PCa), especially androgen-resistant PCa (ARPC), poses a major global health burden shaped by both genetics and environmental exposures. This chapter examines how toxicants like endocrine disruptors, POPs, and xenobiotics contribute to PCa progression through exposomics, toxicogenomics, and multi-omics approaches. It highlights mechanisms such as AR signaling disruption, mitochondrial dysfunction, metabolic shifts, and epigenetic changes driving therapy resistance. Using cell models and spatial transcriptomics, it explores how exposures promote metastasis. The chapter also discusses tools like eDNA, epigenetic biomarkers, and predictive models for early detection and prevention, underscoring the importance of integrating environmental risk into precision oncology.

A series of isonicotinoyl hydrazones have been synthesized via template method and were complexed to Cu(II). The ligands are coordinated to Cu(II) ion through the enolic oxygen and azomethine nitrogen resulting in a square planar geometry. The CT-DNA and bovine serum albumin binding propensities of the compounds were determined spectrophotometrically, the results of which indicate good binding propensity of complexes to DNA and BSA with high binding constant values. Furthermore, the compounds have been investigated for their cytotoxicities on A549 human lung cancer cell. Also the mode of cell death was examined employing various staining techniques and was found to be apoptotic.

Abnormal prostate growth is the most prevalent pathological sign in aged human males, as reflected by high incidence of benign prostate hyperplasia (BPH) and prostate cancer. In spite of the high prevalence, the etiology and pathophysiology of BPH is unclear due to the lack of any established rodent model for study. It has been demonstrated that the cadmium (Cd) mimics the activity of androgen or estrogen by interacting with the steroid hormone receptors in the prostate and elicits BPH, but the specific receptor which binds to Cd is still unknown. Our lab studies with BPH patients highlighted a strong co-relation between smokings with increased Cd content. Changes in the maximum urinary flow rate (Qmax) and prostatic acid phosphatase (PAP) level further supports that Cd can induce BPH like condition. Therefore, the present study was aimed to induce BPH like condition in rats by Cd administration. The dose of cadmium was standardized in an age- and time-dependent manner, which was further examined by prostate weight, histology, and PAP levels that elucidated the pathogenesis of BPH. Further to understand the molecular basis, steroid hormone receptor antagonist experiment was performed. Gene expression and immunohistochemistry data suggest that Cd induces hyperplasia like condition by activating the androgen receptor and estrogen receptor-α and suppresses the action of estrogen receptor-β. The experimental model used here is a cost effective, less time consuming and potentially valuable tool for investigating the respective functions of epithelial and stromal hormone receptors. The applicability of this model would be helpful in understanding the pathogenesis of BPH and its progression.

Benign Prostate hyperplasia (BPH) and prostate cancer (PCa) are the most common prostatic disorders affecting elderly men. Multiple factors including hormonal imbalance, disruption of cell proliferation, apoptosis, chronic inflammation, and aging are thought to be responsible for the pathophysiology of these diseases. Both BPH and PCa are considered to be arisen from aberrant proliferation of prostate stem cells. Recent studies on BPH and PCa have provided significant evidence for the origin of these diseases from stem cells that share characteristics with normal prostate stem cells. Aberrant changes in prostate stem cell regulatory factors may contribute to the development of BPH or PCa. Understanding these regulatory factors may provide insight into the mechanisms that convert quiescent adult prostate cells into proliferating compartments and lead to BPH or carcinoma. Ultimately, the knowledge of the unique prostate stem or stem-like cells in the pathogenesis and development of hyperplasia will facilitate the development of new therapeutic targets for BPH and PCa. In this review, we address recent progress towards understanding the putative role and complexities of stem cells in the development of BPH and PCa.

The association of cadmium (Cd) and lead (Pb) in the pathophysiology and progression of benign prostate hyperplasia (BPH) has been evaluated in an epidemiological study with 116 BPH patients of the western part of India. The prostatic acid phosphatase activity, prostate-specific antigen, maximum urinary flow rate (Q _max), and redox status of BPH patients were correlated with Cd and Pb contents. Additionally, patients were also separated on the basis of their age, genetic lineage, and additive habits and correlated with the Cd, Pb, and Q _max levels. Our results suggest that the accumulation of toxic metals in prostate tissue has a significant positive correlation with the pathogenesis of BPH. Cd and Pb exert their effects through altered antioxidant defense mechanisms, ultimately leading to increased BPH severity. Progression of the pathogenesis also depends on other factors such as additive habits, genetic lineage, and age of the patients.