Curcumin exhibits a broad spectrum of beneficial health properties that include anti-tumor and anti-cancer activities. The down-regulation of c-myc transcription via stabilizing the G-quadruplex structure formed at the promoter region of the human c-myc gene allows the repression in cancer growth. Small molecules can bind and stabilize this structure to provide an exciting and promising strategy for anti-cancer therapeutics. Herein, we investigated the interaction of Curcumin and its synthetic analogs with G-quadruplex DNA formed at the c-myc promoter by using various biophysical and biochemical assays. Further, its cytotoxic effect and mechanistic insights were explored in various cancer cell lines as well as in multicellular tumor spheroid (MCTS) model. The MCTS possesses almost similar microenvironment as avascular tumors, and micro-metastases can be used as a suitable model for the small molecule-based therapeutics development. Our study provides an expanded overview of the anti-cancer effect of a new Curcumin analog via targeting G-quadruplex structures formed at the promoter region of the human c-myc gene.

姜黄素具有广泛的有益健康特性，包括抗肿瘤和抗癌活性。通过稳定在人c-myc基因启动子区域形成的G-四链体结构，c-myc转录的下调可抑制癌症的生长。小分子可以结合并稳定该结构，从而为抗癌治疗提供令人兴奋且有希望的策略。在这里，我们调查了姜黄素及其合成类似物与c-myc上形成的G-四链体DNA的相互作用通过使用各种生物物理和生化测定来启动子。此外，在各种癌细胞系以及多细胞肿瘤球体（MCTS）模型中探索了其细胞毒性作用和机理见解。MCTS具有与无血管肿瘤几乎相似的微环境，微转移可用作基于小分子的治疗药物开发的合适模型。我们的研究通过靶向在人c-myc基因启动子区域形成的G-四链体结构，提供了新姜黄素类似物的抗癌作用的扩展概述。