Elbehairi Serag Eldin I, Ismail Lamia A, Alfaifi Mohammad Y, Elshaarawy Reda F M, Hafez Hani S
Biology Department, Faculty of Science, King Khalid University, 9004 Abha, Saudi Arabia; Cell Culture Lab, Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company), Giza 12311, Egypt; Faculty of Science, Zoology Department, Suez University, 43533 Suez, Egypt.
Department of Chemistry, Faculty of Science, Port Said University, Port Said, Egypt.
Int J Biol Macromol. 2020 Dec 15;165(Pt B):2750-2764. doi: 10.1016/j.ijbiomac.2020.10.153. Epub 2020 Oct 24.
A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs) were used to encapsulate this macromolecular complex, targeting enhancing its therapeutic effect and minimizing its side impacts. The encapsulated Ag(I) complex was significantly triggered apoptosis (P < 0.05) with much more rapidly release of Ag(I)FLLL49-GbA from the CNPs at pH 5.3 than at pH 7.4, which is beneficial for cancer-targeted drug delivery. Free complex showed promising ability in preventing glucose uptake and lactate production coupled with cellular ATP depletion in cancer cells. Additionally, there was significant decrease in the inflammatory cytokines in breast cancer (MCF-7) and lung cancer (A549) cells with values of P < 0.01 and P < 0.001 after 24 h incubation. Furthermore, the death-inducing proteins have been significantly up-regulated (P < 0.01 to P < 0.001) after 36 h incubation of cancer cells. Consequently, the novel curcuminoid macromolecule showed significant feasibility in triggering the high expression of apoptotic caspases caspase 3, caspase 8, P53, and Bax (P < 0.01 to P < 0.001) after 48 h of chemotherapy. Noteworthy, the cytotoxicity of Ag(I)FLLL49-GbA was significantly increased toward cancer cells (MCF-7 > A549), while, reduced toward normal cells (HeLa) after loading on chitosan Nano-vehicles.
一种基于姜黄素类化合物 - Gboxin类似物（FLLL49 - GbA）及其大分子银（I）配合物（Ag（I）FLLL49 - GbA）的新型抗癌和抗炎剂已成功合成。此外，壳聚糖纳米颗粒（CNPs）被用于包裹这种大分子配合物，旨在增强其治疗效果并最小化其副作用。包裹的Ag（I）配合物在pH 5.3时比在pH 7.4时能显著触发细胞凋亡（P < 0.05），且Ag（I）FLLL49 - GbA从CNPs中的释放速度更快，这有利于癌症靶向给药。游离配合物在抑制癌细胞摄取葡萄糖和产生乳酸以及导致细胞ATP消耗方面显示出良好的能力。此外，在乳腺癌（MCF - 7）和肺癌（A549）细胞中，孵育24小时后炎症细胞因子显著减少，P值分别为P < 0.01和P < 0.001。此外，癌细胞孵育36小时后，诱导死亡的蛋白显著上调（P < 0.01至P < 0.001）。因此，新型姜黄素类大分子在化疗48小时后显示出显著的可行性，可触发凋亡半胱天冬酶caspase 3、caspase 8、P53和Bax的高表达（P < 0.01至P < 0.001）。值得注意的是，负载在壳聚糖纳米载体上后，Ag（I）FLLL49 - GbA对癌细胞（MCF - 7 > A549）的细胞毒性显著增加，而对正常细胞（HeLa）的细胞毒性降低。
