Beta-Sitosterol Alters Collagen Distribution in Prostate Fibroblasts

Abstract

Herbal supplements containing several types of plant sterols, vitamins, and minerals, are marketed for prostate health. In the majority of these supplements, the most abundant plant sterol is saw palmetto extract or its’ principal component, beta-sitosterol. In terms of prostate health, previous work almost exclusively focused on the effects of beta-sitosterol on prostatic epithelium, with little attention paid to the effects on prostatic stroma. This omission is a concern, as the abnormal accumulation of collagen, or fibrosis, of the prostatic stroma has been identified as a factor contributing to lower urinary tract symptoms and dysfunction in aging men. To address whether beta-sitosterol may be promoting prostatic fibrosis, immortalized and primary prostate stromal fibroblasts were subjected to immunoblotting, immunofluorescence, qRT-PCR, ELISA, and image quantitation and analysis techniques to elucidate the effects of beta-sitosterol on cell viability and collagen expression and cellular localization. The results of these studies show that beta-sitosterol is nontoxic to prostatic fibroblasts and does not stimulate collagen production by these cells. However, beta-sitosterol alters collagen distribution and sequesters collagen within prostatic fibroblasts, likely in an age-dependent manner. This is a significant finding as prostate health supplements are used predominantly by middle aged and older men who may, then, be affected disproportionately by these effects.

Keywords:

• Beta-sitosterol
• collagen
• fibroblast
• prostate
• stroma
• supplement

Acknowledgements

The authors would like to acknowledge the Alton J. Brann Foundation Endowment (J.A.M.) for supporting this work and for services provided by the CPCT Genomics Core supported by NIH/NCI U54 CA156734 (J.Am).

Disclosure statement

The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Quentin D’Arcy

Quentin D’Arcy, B.S., is a Biology pre-doctoral student at the University of Massachusetts Boston. He earned a B.S. in Biology with Honors from the University of Massachusetts Amherst and spent several years at the Massachusetts Department of Health prior to joining the Macoska laboratory in 2020. His dissertation research focuses on mechanisms promoting fibrosis in the lower urinary tract including those involving pro-fibrotic cytokines, health supplements, and regulatory RNAs. He plans to pursue a position in academia or industry in the Boston/Cambridge area upon completion of his graduate studies.

Marissa Sarna-McCarthy

Marissa Sarna-McCarthy, B.S., is a Biology pre-doctoral student at the University of Massachusetts Boston. She earned a B.S. in Biology from Bay Path University while working part time as a chemistry lab preparatory technician at the Baystate Medical Center prior to joining the Macoska laboratory in 2020. Her dissertation research focuses on cytokine-induced anti-apoptotic mechanisms that increase the survival of activated fibroblasts and myofibroblasts, hence, promote collagen production and fibrosis in the lower urinary tract. She plans to remain in Massachusetts and pursue a position in academia or industry upon completion of his graduate studies.

Delaney Bowen

Delaney Bowen, B.S., is a Biology Master’s student and the President of the Graduate Student Association at the University of Massachusetts Boston. She earned a B.S. in Biology from the University of Massachusetts Boston in 2021 and joined the Macoska Laboratory the following year. Her thesis research focuses on the role(s) of regulatory RNAs, particularly miRNAs, in promoting fibrosis in the lower urinary tract. Upon graduation, she plans to attend medical school to become a physician scientist.

Fidias O. Soto

Fidias Soto, B.S., graduated from the University of Massachusetts Boston with a B.S. in Biology with Honors and Distinction in 2023. As an undergraduate student, he received the College of Science and Mathematics Undergraduate Research Fellowship, the McCone Award, and Biology Department Research Award. He is now pursuing a patient-centered position in the Harvard health and hospital system and plans to attend medical school to become a physician scientist.

Kourosh Zarringhalam

Kourosh Zarringhalam, Ph.D., is an Associate Professor in the Department of Mathematics at the University of Massachusetts Boston. His research utilizes approaches from applied mathematics, data sciences, and computational molecular biology to develop mathematical models and algorithms for parasitology and cancer applications.

Jill A. Macoska

Jill Macoska, Ph.D., is the Distinguished University Professor of Science and Mathematics, Alton J. Brann Endowed Chair, and Director of the Center for Personalized Cancer Therapy and Genomics Core at the University of Massachusetts Boston. She has led peer-reviewed and NIH-funded research for the past 30 years focused on elucidating the molecular genetic alterations and dysfunctional inter- and intra- cellular signaling mechanisms that promote urinary tract (kidney, bladder, prostate) pathobiology. This work has resulted in >100 peer-reviewed publications, many of which were co-authored by the >50 post-doctoral, pre-doctoral, or undergraduate trainees she has mentored in her laboratory. Notably, the Macoska laboratory established the concept of peri-urethral fibrosis as a pathobiology promoting male lower urinary dysfunction (LUTD), a finding that has since become a major driving force towards understanding and treating LUTD.