Abstract 1035: MS13 (1, 5-bis (4-hydroxy-3-methanoxyphenyl)-1, 4-pentadiene-3-one) exhibits anti-cancer properties in androgen-independent prostate cancer cells

Abstract

Prostate cancer (PCa) is the most frequent malignancy among men. Most PCa patients initially respond to androgen deprivation therapy (ADT) but eventually gain androgen-independent properties (AIPC), which are currently incurable and develop resistance to treatment. Thus, novel therapeutic agents with fewer side effects to treat AIPC is urgently needed. Diarylpentanoid [1, 5-bis (4-hydroxy-3-methanoxyphenyl)-1, 4-pentadiene-3-one] (MS13), a curcumin analogue, demonstrated dose- and time-dependent growth inhibitory effects on AIPC cells. However, the anti-cancer effects of MS13 on AIPC cells have not been extensively studied. This study aims to investigate the expression of genes associated with Notch, Hedgehog, and chromatin condensation pathways in MS13-treated DU 145 cells. In our previous study, MS13 exhibited greater cytotoxicity effects than curcumin in DU 145 cells with lower EC50 values (approximately 8 µM and 35 µM, respectively). The gene expression analysis of MS13-treated DU 145 cells was further explored using nCounter PanCancer Pathway Panel (Nanostring Technologies, USA). Briefly, DU 145 cells were treated with two times of EC50 value (16 µM) of MS13 for 24 hours. The RNA was extracted from treated and controls cells using the RNeasy Mini Kit (Qiagen, USA). Genes with a filter of two-fold-cut-off, p. adjusted ≤ 0.05, and FDR≤ 0.05 were defined as significant differentially expressed genes (DEGs). The finding demonstrated that several genes were significantly altered in MS13-treated DU 145 cells at 16 µM for 24 hours, in comparison with the controls. A total of 7 significantly DEGs associated with Notch, Hedgehog, and chromatin condensation pathways were selected for further analysis. The DEGs associated with Notch pathway including Jagged Canonical Notch Ligand 1 (JAG1), Delta Like Canonical Notch Ligand 4 (DLL4) and Notch Receptor 1 (NOTCH1) were upregulated, and shown to mediate anti-proliferative, apoptosis as well as inhibit metastasis and angiogenic properties in cancer cells. Meanwhile, the DEGs associated with Hedgehog pathway; Protein Kinase CAMP-Activated Catalytic Subunit Beta (PRKACB), Wnt Family Member 7B (WNT7B), Wnt Family Member 5B (WNT5B) and Chromatin condensation; Histone Deacetylase 6 (HDAC6) were downregulated and implicated in cancer progression, tumorigenesis, metastasis, and cell migration. Moreover, genes such as NOTCH1, PRKACB, WNT7B, and WNT5B were involved in multiple signaling pathways, displaying greater growth inhibition. In conclusion, the findings suggest that MS13 may demonstrate anti-cancer effects through modulating key canonical pathways that enhances tumor-suppressive and inhibits oncogenic genes, indicating a potential therapeutic agent for AIPC. Citation Format: Nurul Azwa Abd. Wahab, Iekhsan Othman, Faridah Abas, Rakesh Naidu. MS13 (1, 5-bis (4-hydroxy-3-methanoxyphenyl)-1, 4-pentadiene-3-one) exhibits anti-cancer properties in androgen-independent prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1035.