Sanguinarine targets BRD4 to suppress cell proliferation and migration in clear cell renal cell carcinoma

Abstract

Sanguinarine is an alkaloid with diverse biological activities, nevertheless, whether it can target epigenetic modifiers remains unknown. In this study, sanguinarine was characterized as a strong BRD4 inhibitor with IC50 = 361.3 nM against BRD4 (BD1) and IC50 = 302.7 nM against BRD4 (BD2) that can inactivate BRD4 reversibly. Additional cellular assays suggested that sanguinarine can bind BRD4 in human clear cell renal cell carcinoma (ccRCC) cell line 786‐O and inhibit cell growth with IC50 (24 h) = 0.6752 μM and IC50 (48 h) = 0.5959 μM in a BRD4 dependent manner partially. Meanwhile, sanguinarine can inhibit the migration of 786‐O cells in vitro and in vivo, and reverse epithelial−mesenchymal transition. Moreover, it can inhibit 786‐O cells proliferation in vivo in a BRD4 dependent manner partially. In sum, our study identified BRD4 as a new target of sanguinarine, and sanguinarine may serve as a potential therapeutic agent against ccRCC.

Insights on Antitumor Activity and Mechanism of Natural Benzophenanthridine Alkaloids

“…To be specific, the most potent activity is observed against drug-resistant HL-60/MX2 with IC 50 values of 0.10 ± 0.05 [ 25 ]. Sanguinarine ( 1 ) can inhibit the migration of 786-O cells in vitro and in vivo, and reverse the epithelial−mesenchymal transition with IC 50 values of 0.5959 μM [ 26 ].…”