白藜芦醇的白蛋白纳米包封通过下调核p65和HIF-1α增强其在结肠癌中的抗癌潜力。

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α.

作者信息

Aljabali Alaa A A, Bakshi Hamid A, Hakkim Faruk L, Haggag Yusuf A, Al-Batanyeh Khalid M, Al Zoubi Mazhar S, Al-Trad Bahaa, Nasef Mohamed M, Satija Saurabh, Mehta Meenu, Pabreja Kavita, Mishra Vijay, Khan Mohammed, Abobaker Salem, Azzouz Ibrahim M, Dureja Harish, Pabari Ritesh M, Dardouri Ashref Ali K, Kesharwani Prashant, Gupta Gaurav, Dhar Shukla Shakti, Prasher Parteek, Charbe Nitin B, Negi Poonam, Kapoor Deepak N, Chellappan Dinesh Kumar, Webba da Silva Mateus, Thompson Paul, Dua Kamal, McCarron Paul, Tambuwala Murtaza M

机构信息

Department of Pharmaceutical Sciences, Yarmouk University-Faculty of Pharmacy, Irbid 566, Jordan.

School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK.

出版信息

Cancers (Basel). 2020 Jan 1;12(1):113. doi: 10.3390/cancers12010113.

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-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α 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 therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.

已知白皮杉醇（PIC）具有抗癌活性，这归因于其通过抑制核因子-κB（NF-κB）信号通路来阻断癌细胞增殖的能力。然而，其在癌症中对缺氧诱导因子（HIF）的影响尚不清楚。在本研究中，通过去溶剂化方法将PIC负载到牛血清白蛋白（BSA）中制成PIC-BSA纳米颗粒（NPs）。对这些PIC-BSA纳米颗粒进行了体外细胞毒性、迁移、侵袭和集落形成研究以及p65和HIF-1α水平的检测。我们的结果表明，与游离PIC相比，PIC-BSA NPs在下调结肠癌细胞中核p65和HIF-1α的表达方面更有效。我们还观察到PIC-BSA NPs可显著减轻小鼠化学性结肠炎诱导的炎症。此外，在结肠炎相关结直肠癌的小鼠模型中，与游离PIC相比，用PIC-BSA NPs治疗时肿瘤大小和结肠肿瘤数量也显著减少。总体结果表明，PIC制成PIC-BSA NPs后可增强其治疗潜力。我们的工作可能会促使进一步研究将天然抗癌剂制成纳米颗粒并进行可能的人体临床试验。这可能会为癌症患者开发出一系列新的安全有效的治疗方法。