2'-HYDROXY-2,4,4',5,6'-PENTAMETHOXYCHALCONE

Rubone, a chalcone analog, is a modulator of miR-34a. Rubone upregulates miR-34a expression in a p53 dependent manner, downregulates the downstream target Bcl-2 and Cyclin D1 expression, and suppresses hepatocellular carcinoma (HCC) growth in vivo. Rubone enhances the anticancer effect of Paclitaxel (PTX; HY-B0015) in PTX-resistant prostate cancer cell lines by reversing the expression of miR-34a downstream targets[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> MicroRNA

Rubone (0-60 μM) 在 DU145-TXR 和 PC3-TXR 细胞中表现出显着的细胞毒性，表明 Rubone 在晚期前列腺癌细胞中具有更强的抗癌作用，这些细胞具有较低的 miR-34a 表达[3]。 Rubone (5, 10 uM; 48 小时) 显着逆转 DU145-TXR 和 PC3-TXR 细胞系的 miR-34a 下游基因靶标的表达。Rubone 以剂量依赖性方式上调 PTX 抗性 DU145-TXR 和 PC3-TXR 细胞系中的 miR-34a[3]。 Rubone (5 μM; 持续 2 周) 和 PTX (持续 2 周) 联合疗法抑制 3D 模型中的 PC3-TXR 细胞生长和球体形成，包括顶部 3D 和悬滴模型。Rubone 和 PTX 联合疗法抑制 p53 独立途径中的细胞侵袭、迁移和癌症干细胞样细胞 (CSC) 种群。Rubone 单一疗法或 Rubone 与 PTX 组合可显着增强 TAp73 和 Elk-1 的表达[3]。 Cell Cytotoxicity Assay[3] Cell Line: DU145, PC3, PTX resistant DU145-TXR, PC3-TXR, LNCaP, LNCaP developed C4-2 cells Concentration: 0-60 μM Incubation Time: Result: Exhibited significantly higher cytotoxicity in DU145-TXR and PC3-TXR cells. Western Blot Analysis[3] Cell Line: DU145-TXR and PC3-TXR cell lines Concentration: 5, 10 uM Incubation Time: 48 h Result: Significantly reversed the expression of miR-34a downstream gene targets of DU145-TXR and PC3-TXR cell lines, including E-cadherin, SIRT1, and Cyclin D1, whereas E-cadherin expression was not reversed in DU145-TXR cell line. Real Time qPCR[3] Cell Line: DU145-TXR and PC3-TXR cell lines Concentration: 5, 10 uM Incubation Time: 48 h Result: Upregulated miR-34a in PTX-resistant DU145-TXR and PC3-TXR cell lines in a dose dependent manner.

Rubone 单一疗法 (装载 20 mg/kg 的 PEG-PCD 胶束; 每隔一天静脉注射; 共五剂) 或与 PTX 联合治疗 (PEG-PCD 胶束装载每种药物 10 mg/kg) 显着上调肿瘤中的 miR-34a 表达。联合疗法抑制肿瘤生长。Rubone 单一疗法未能抑制肿瘤细胞增殖[3]。 Animal Model: 8 weeks old male nude mice transfected prostate cancer cells[3] Dosage: 20 mg/kg or 10 mg/kg for each drug (PTX and Rubone) loaded PEG-PCD micelles Administration: Intravenously for five doses every other day Result: Had little effect on body weight loss and inhibited tumor growth. Monotherapy or combination therapy with PTX significantly upregulated miR-34a expression in tumor. Alone or with PTX significantly reversed E-cadherin, Cyclin D1, and SIRT1 expression.

[1]. Zhangang Xiao, et al. Small molecule targeting miR-34a for cancer therapy. Mol Cell Oncol. 2015 Feb 24;2(1):e977160.  

[2]. Lu Zhang, et al. MicroRNA-34 family: a potential tumor suppressor and therapeutic candidate in cancer. J Exp Clin Cancer Res. 2019 Feb 4;38(1):53.  

[3]. Di Wen, et al. Micellar Delivery of miR-34a Modulator Rubone and Paclitaxel in Resistant Prostate Cancer. Cancer Res. 2017 Jun 15;77(12):3244-3254.