Abstract 3609: Interaction of interleukin-6/8/18 with prostate cancer cell secreted growth factors are crucial for osteoblast proliferation and differentiation

Abstract

Abstract There is currently no effective therapy for bone metastatic prostate cancer, which is the main cause of mortality in people with prostate cancer. Poor prognosis of bone metastasis has limitations in current therapeutics mainly due to the complexity of microenvironment. Our focus was on the interactions between prostate cancer cells and the bone microenvironment, including osteoclasts and osteoblasts in regard to growth factors and cytokines, as the bone microenvironment plays a significant role in this process. The present study shows the downstream effects of Stavudine (KB-S); a known antiviral compound along with 5-fluoro-1-((1R,4R)-4-((tetrahydro-2H-pyran-2-yl)oxy)cyclopent-2-en-1-yl)pyrimidine-2,4(1H,3H)-dione (KB-G) and 1-((1R,4R)-4-hydroxycyclopent-2-en-1-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (KB-H) on bone metastatic prostate cancer. Effects of KB-G/H and S on HEK-293 control cells were determined as moderate under tested conditions. A series of KB-G/H and S (10, 25, 50, 75 and 100 µM) was given for a 4-day period (with 24 h intervals) and the prostate cancer cell population was determined at the end of the 4-day treatment period. Preliminary results indicated that all 3 compounds significantly decreased DU-145 and PC-3 cell population compared to the effects on HEK-293 cells. Results suggested that all 3 compounds can decrease the prostate cancer cell progression by enhancing apoptosis. Our data also suggested that all 3 compounds downregulated interleukin (IL)-18, IL-8, IL-6 and C-X-C motif ligand-1(CXCL-1) in prostate cancer cells (PC-3 and DU-145). A human osteoblast cell line (hFOB 1.19) is being used to study the effect of cytokines in relation to transforming growth factor β (TGFβ), insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) that are secreted by prostate cancer cells. In-vitro migration/invasion assays, immunoprecipitation (IP), immunofluorescence microscope, cytokine profile array, real time qPCR and Western blot techniques are being used in this study to further analyze role of cytokines and growth factors on osteoblast differentiation. Our preliminary results suggest that all 3 compounds can be used to disrupt the main steps of prostate cancer bone metastasis. Results suggested that KB-G/H and S can be targeted to develop customized, tailored therapies for bone metastatic prostate cancer which merit further research. Citation Format: Aaron Jeshua Todman, Wishrawana S. Ratnayake, Luke Lajmi, Sloan Breedy, Kirpal Bisht, Mildred Acevedo-Duncan. Interaction of interleukin-6/8/18 with prostate cancer cell secreted growth factors are crucial for osteoblast proliferation and differentiation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3609.