School of Medicine, Ardabil University of Medical Science, Ardabil, 56197, Iran.
Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
Sci Rep. 2017 May 31;7(1):2559. doi: 10.1038/s41598-017-02666-4.
Curcumin and its chalcone derivatives inhibit the growth of human cancer cells. It is reported that replacement of two OH groups in curcumin with less polar groups like methoxy increases its anti-proliferative activity. In this study, we explored benzylidine cyclohexanone derivatives with non-polar groups, to see if they possess increased anti-cancer activity. Novel 2,6-bis benzylidine cyclohexanone analogues of curcumin were synthesized, and their inhibitory effects on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells were studied using an MTT assay. Cell apoptosis was detected by EB/AO staining, and cell cycle was analyzed by flow cytometry. Real-time PCR was performed for gene expression analysis. All synthesized analogues were cytotoxic toward gastric and esophageal cancer cells and showed lower IC values than curcumin. Treatment with 2,6-Bis-(3-methoxy-4-propoxy-benzylidene)-cyclohexanone (BM2) was 17 times more toxic than curcumin after 48 h incubation. All novel compounds were more effective than curcumin in apoptosis induction and cell cycle arrest at G1 phase. These results suggest that less polar analogues of curcumin have potent cytotoxicity in vitro. However, they need to be investigated further, especially with animal tumor models, to confirm their chemotherapeutic activity in vivo.
姜黄素及其查尔酮衍生物能抑制人类癌细胞的生长。有报道称，用极性较小的甲氧基取代姜黄素中的两个羟基，能提高其抗增殖活性。在这项研究中，我们探索了具有非极性基团的苄叉环己酮衍生物，以观察它们是否具有更强的抗癌活性。合成了姜黄素的新型 2,6-双苄叉环己酮类似物，并通过 MTT 法检测它们对胃腺癌（AGS）和食管鳞状细胞癌（KYSE30）癌细胞的抑制作用。通过 EB/AO 染色检测细胞凋亡，通过流式细胞术分析细胞周期。通过实时 PCR 进行基因表达分析。所有合成的类似物对胃和食管癌细胞均具有细胞毒性，且 IC 值均低于姜黄素。在 48 h 孵育后，2,6-双（3-甲氧基-4-正丙氧基-苄叉）环己酮（BM2）的毒性比姜黄素高 17 倍。与姜黄素相比，所有新化合物在诱导细胞凋亡和 G1 期细胞周期阻滞方面更有效。这些结果表明，姜黄素的极性较小类似物具有很强的体外细胞毒性。然而，还需要进一步研究，特别是在动物肿瘤模型中，以确认它们在体内的化疗活性。
