title: Arecoline augments cellular proliferation in the prostate gland of male Wistar rats.
abstract: Areca nut chewing is the fourth most popular habit in the world due to its effects as a mild stimulant, causing a feeling of euphoria and slightly heightened alertness. Areca nuts contain several alkaloids and tannins, of which arecoline is the most abundant and known to have several adverse effects in humans, specially an increased risk of oral cancer. On evaluating the effects of arecoline on the male endocrine physiology in Wistar rats, it was found that arecoline treatment led to an overall enlargement and increase in the wet weight of the prostate gland, and a two-fold increase in serum gonadotropin and testosterone levels. Since the prostate is a major target for testosterone, the consequences of arecoline consumption were studied specifically in the prostate gland. Arecoline treatment led to an increase in the number of rough endoplasmic reticulum and reduction of secretory vesicles, signifying a hyperactive state of the prostate. Increased expression of androgen receptors in response to arecoline allowed for enhanced effect of testosterone in the prostate of treated animals, which augmented cell proliferation, subsequently confirmed by an increase in the expression of Ki-67 protein. Cellular proliferation was also the outcome of concomitant over expression of the G(1)-to-S cell cycle regulatory proteins, cyclin D1 and CDK4, both at the transcriptional and translational levels. Taken together, the findings provide the first evidence that regular use of arecoline may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders associated with prostate enlargement.
authors: Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata-700019, India.
authors: Indraneel
authors: I
authors: Saha
authors: Aniruddha
authors: A
authors: Chatterjee
authors: Anushree
authors: A
authors: Mondal
authors: Bishwa Ranjan
authors: BR
authors: Maiti
authors: Urmi
authors: U
authors: Chatterji
mesh_terms: D000818:Animals; D001115:Arecoline / Q000494:pharmacology*; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005640:Follicle Stimulating Hormone / Q000097:blood; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D046529:Microscopy, Electron, Transmission; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood
chemical_list: D019394:Ki-67 Antigen; D019938:Cyclin D1; D013739:Testosterone; D001115:Arecoline; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D051358:Cyclin-Dependent Kinase 4