Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α
Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α
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DOI：
10.3390/cancers12010113
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Tambuwala, Murtaza M.
中科院分区：
文献类型：
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作者：
Aljabali, Alaa A. A.;Bakshi, Hamid A.;Tambuwala, Murtaza M.
已知Piceatannol（PIC）具有抗癌活性，这归因于其通过抑制NF-κ B信号传导途径阻断癌细胞增殖的能力。然而，它对缺氧诱导因子（HIF）的作用在癌症中并不为人所知。采用去溶剂化法将PIC负载于牛血清白蛋白（BSA）表面，制备了PIC-BSA纳米粒。评估这些PIC-BSA纳米颗粒的体外细胞毒性、迁移、侵袭和集落形成研究以及p65和HIF-1 α的水平。我们的研究结果表明，PIC-BSA纳米颗粒在下调结肠癌细胞中的核p65和HIF-1 α的表达方面比游离PIC更有效。我们还观察到通过PIC-BSA NP在小鼠中由化学性结肠炎诱导的炎症显著减少。此外，与游离PIC相比，当用PIC-BSA NP处理时，在结肠炎相关结肠直肠癌的鼠模型中也观察到肿瘤大小和结肠肿瘤数量的显著减少。总体结果表明，PIC，当配制成PIC-BSA NP时，增强了其治疗潜力。我们的工作可以促进进一步的研究，使用天然抗癌药物作为纳米粒子与可能的人类临床试验。这可能导致为癌症患者开发一种新的安全有效的治疗方法。
Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1 alpha. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1 alpha in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.