Abstract 4975: Anti-cancer effect of a probiotic bacteria-derived compound, 1,4-Dihydroxy-2-naphthoic acid in prostate cancer

Abstract

Abstract Cancer incidence has been increasing globally and the major cause for mortality associated with this disease is due to metastasis development. Followed by skin and lung cancer, prostate cancer (PCa) is one of the most common cancers prevailing among older men in the United States. Although androgen deprivation therapy (ADT) is the mainstay treatment for PCa, most patients undergoing ADT eventually develop metastatic PCa. Moreover, other treatment options, such as chemotherapy and radiotherapy, have toxic side effects and are ineffective in controlling advanced PCa. Hence, there arises a need for identifying alternative agents with possibly fewer side effects. The gut biome plays a significant role in regulating many bodily functions like digestion, immunity, and including cancer prevention. Probiotics, commonly known as 'good bacteria,' are living microorganisms that provide health promoting benefits. A probiotic metabolite, 1,4-Dihydroxy-2-naphthoic acid (DHNA), is an anti-inflammatory aryl hydrocarbon receptor (Ahr) agonist which is yet to be explored for its anticancer activity. Inhibiting the inflammatory signaling axis and activating Ahr by DHNA could be a promising strategy to counteract metastatic PCa. Cell viability assays revealed that 1,4-DHNA is highly toxic in metastatic prostate cancer cell lines such as DU145 and PC3 compared to normal prostate epithelial cells like RWPE-1 and human prostate stromal myofibroblast cell line, WPMY-1, with an approximate IC50 value of 5 µM in DU145 and PC3 and about 20 µM and 75 µM in WPMY-1 and RWPE-1 respectively. DHNA reduced the colony forming abilities of BPH-Cd, PC3, and DU145 in clonogenic assay and suppressed the BPH-Cd spheroid growth in spheroid formation assay, revealing its anti-tumorigenic potential. Trans-well migration assay using BPH-Cd, PC3, and DU145 showed a decrease in cell migration, hinting at the drug's anti-metastatic ability. G2/M phase arrest in cell cycle analysis and dose-dependent increase in apoptosis of DHNA-treated DU145, PC3, and LNCaP cell lines reiterated its anti-cancer potential. Western blot results in PC3 and DU145 showed significant dose-dependent inhibition of protooncogene β-catenin expression. Downregulation of cell cycle proteins like cyclin D1 and increased expression of effector caspase, cleaved caspase 7 support cell death promoting effects of DHNA via an intrinsic apoptotic pathway. Our pre-clinical data suggest that DHNA can be a potential drug for inhibiting both prostate tumor growth and metastasis. Further research is warranted to ascertain the anti-metastatic and underlying anti-cancer mechanisms to help translate the findings to clinical use. Citation Format: Shreeja Srinivas Bitla, Gnanasekar Munirathinam. Anti-cancer effect of a probiotic bacteria-derived compound, 1,4-Dihydroxy-2-naphthoic acid in prostate cancer. [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 4975.