Exposure of androgen mimicking environmental chemicals enhances proliferation of prostate cancer (LNCaP) cells by inducing AR expression and epigenetic modifications
| Autor: | Gauri Misra, Pradeep Kumar Sharma, Rajesh Pal, Vipendra Kumar Singh, Yogeshwer Shukla, Priyansh Srivastava |
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| Rok vydání: | 2020 |
| Předmět: |
Male
010504 meteorology & atmospheric sciences medicine.drug_class Health Toxicology and Mutagenesis Genistein 010501 environmental sciences urologic and male genital diseases Toxicology 01 natural sciences Epigenesis Genetic chemistry.chemical_compound Prostate cancer Cell Line Tumor LNCaP medicine Humans Epigenetics 0105 earth and related environmental sciences Cell Proliferation Prostatic Neoplasms Androgen Antagonists General Medicine Androgen medicine.disease Pollution HDAC1 Androgen receptor chemistry Receptors Androgen DNMT1 Cancer research Androgens |
| Zdroj: | Environmental pollution (Barking, Essex : 1987). 272 |
| ISSN: | 1873-6424 |
| Popis: | Exposure to environmental endocrine disrupting chemicals (EDCs) is highly suspected in prostate carcinogenesis. Though, estrogenicity is the most studied behavior of EDCs, the androgenic potential of most of the EDCs remains elusive. This study investigates the androgen mimicking potential of some common EDCs and their effect in androgen-dependent prostate cancer (LNCaP) cells. Based on the In silico interaction study, all the 8 EDCs tested were found to interact with androgen receptor with different binding energies. Further, the luciferase reporter activity confirmed the androgen mimicking potential of 4 EDCs namely benzo[a]pyrene, dichlorvos, genistein and β-endosulfan. Whereas, aldrin, malathion, tebuconazole and DDT were reported as antiandrogenic in luciferase reporter activity assay. Next, the nanomolar concentration of androgen mimicking EDCs (benzo[a]pyrene, dichlorvos, genistein and β-endosulfan) significantly enhanced the expression of AR protein and subsequent nuclear translocation in LNCaP cells. Our In silico studies further demonstrated that androgenic EDCs also bind with epigenetic regulatory enzymes namely DNMT1 and HDAC1. Moreover, exposure to these EDCs enhanced the protein expression of DNMT1 and HDAC1 in LNCaP cells. These observations suggest that EDCs may regulate proliferation in androgen sensitive LNCaP cells by acting as androgen mimicking ligands for AR signaling as well as by regulating epigenetic machinery. Both androgenic potential and epigenetic modulatory effects of EDCs may underlie the development and growth of prostate cancer. |
| Databáze: | OpenAIRE |
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