Recent developments in the literature have demonstrated that curcumin exhibit antioxidant properties supporting its anti-inflammatory, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Despite the valuable findings of curcumin against different cancer cells, the clinical use of curcumin in cancer treatment is limited due to its extremely low aqueous solubility and instability, which lead to poor in vivo bioavailability and limited therapeutic effects. We therefore focused in the present study to evaluate the anti-tumor potential of curcumin analogues on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC₅₀ values of curcumin analogue J1 in these cancer cell lines were determined to be 5 ng/ml and 10 ng/ml, in MDA-MB-231 and MCF-7 cells respectively. Interestingly, at these concentrations, the J1 did not affect the viability of non-tumorigenic normal breast epithelial cells MCF-10. Furthermore, we found that J1 strongly induced growth arrest of these cancer cells by modulating the mitochondrial membrane potentials without significant effect on normal MCF-10 cells using JC-1 staining and flow cytometry analysis. Using annexin-V/PI double staining assay followed by flow cytometry analysis, we found that J1 robustly enhanced the induction of apoptosis by increasing the activity of caspases in MDA-MB-231 and MCF-7 cancer cells. In addition, treatment of breast cancer cells with J1 revealed that, in contrast to the expression of cyclin B1, this curcumin analogue vigorously decreased the expression of cyclin A, CDK2 and cyclin E and subsequently sensitized tumor cells to cell cycle arrest. Most importantly, the phosphorylation of AKT, mTOR and PKC-theta in J1-treated cancer cells was markedly decreased and hence affecting the survival of these cancer cells. Most interestingly, J1-treated cancer cells exhibited a significant inhibition in the activation of RhoA followed by reduction in actin polymerization and cytoskeletal rearrangement in response to CXCL12. Our data reveal the therapeutic potential of the curcumin analogue J1 and the underlying mechanisms to fight breast cancer cells.

文献中的最新进展表明，姜黄素具有抗氧化特性，支持其针对侵袭性和复发性癌症的抗炎，化学预防和抗肿瘤活性。尽管姜黄素针对不同癌细胞具有有价值的发现，但由于姜黄素的极低水溶性和不稳定性，其在癌症治疗中的临床应用受到限制，这导致体内生物利用度差和有限的治疗效果。因此，我们将重点放在本研究上，以评估姜黄素类似物对人乳腺癌细胞MDA-MB-231和MCF-7的抗肿瘤潜力，以及它们对非致瘤性正常乳腺上皮细胞（MCF- 10）。IC ₅₀在这些癌细胞系中，姜黄素类似物J1的值在MDA-MB-231和MCF-7细胞中分别确定为5 ng / ml和10 ng / ml。有趣的是，在这些浓度下，J1不会影响非致瘤性正常乳腺上皮细胞MCF-10的活力。此外，我们发现J1通过调节线粒体膜电位而强烈诱导了这些癌细胞的生长停滞，而使用JC-1染色和流式细胞仪分析对正常的MCF-10细胞没有明显影响。使用膜联蛋白-V / PI双重染色测定法，然后进行流式细胞术分析，我们发现J1通过增加MDA-MB-231和MCF-7癌细胞中的半胱天冬酶活性来稳固地增强了细胞凋亡的诱导。此外，用J1处理乳腺癌细胞后发现，与细胞周期蛋白B1的表达相反，该姜黄素类似物可显着降低细胞周期蛋白A，CDK2和细胞周期蛋白E的表达，并随后使肿瘤细胞对细胞周期停滞敏感。最重要的是，经J1处理的癌细胞中AKT，mTOR和PKC-θ的磷酸化明显降低，因此影响了这些癌细胞的存活。最有趣的是，经J1处理的癌细胞对RhoA的激活表现出显着的抑制作用，随后响应CXCL12的肌动蛋白聚合反应和细胞骨架重排减少。我们的数据揭示了姜黄素类似物J1的治疗潜力以及对抗乳腺癌细胞的潜在机制。经J1处理的癌细胞中的mTOR和PKC-theta明显降低，因此影响了这些癌细胞的存活。最有趣的是，经J1处理的癌细胞对RhoA的激活表现出显着的抑制作用，随后响应CXCL12的肌动蛋白聚合反应和细胞骨架重排减少。我们的数据揭示了姜黄素类似物J1的治疗潜力以及对抗乳腺癌细胞的潜在机制。经J1处理的癌细胞中的mTOR和PKC-theta明显降低，因此影响了这些癌细胞的存活。最有趣的是，经J1处理的癌细胞对RhoA的激活表现出显着的抑制作用，随后响应CXCL12的肌动蛋白聚合反应和细胞骨架重排减少。我们的数据揭示了姜黄素类似物J1的治疗潜力以及对抗乳腺癌细胞的潜在机制。