Rady Hanaa, Salem Sohair, Ez El-Arab Mohamed
Chemistry of Natural Compound Department, National Research Centre, Cairo, Egypt.
Molecular Genetics and Enzymology Department, National Research Centre, Cairo, Egypt.
J Pharm Anal. 2019 Aug;9(4):284-291. doi: 10.1016/j.jpha.2019.03.008. Epub 2019 Mar 22.
Cancer recurrence and severe side effects of currently being used chemotherapeutic agents reduce their clinical efficacy. Thus, there is a constant need to develop alternative anticancer drugs. Sustainable supply is an important challenge facing marine-based drug discovery. Primmorph, a 3D cell culture system, could provide a sustainable source to produce metabolites for anticancer drugs from marine sponges. In the present work, the anticancer activity of primmorph extracts and mesohyls of , , and sponges was evaluated. Antiproliferative activity was studied in terms of cytotoxicity, colony formation, cell cycle, and apoptosis. Migration was assessed by migration assay and matrix metalloproteinase activity. The expression of proliferation and migration-related genes was analyzed using real time PCR. Migration and proliferation activities of HepG2 cells were inhibited by treatment with primmorph extracts and mesohyls of , , and . The mesohyl of did not show any anticancer activity although the primmorph extract led to cell cycle arrest. Among the selected sponge species, the primmorph extract of was the most promising anticancer agent regarding antiproliferative and antimigratory activities. In addition, primmorph extracts have the advantage of working under well-defined and controlled conditions, which allows the easy application as a bioreactor.
癌症复发以及目前使用的化疗药物的严重副作用降低了它们的临床疗效。因此,持续需要开发替代的抗癌药物。可持续供应是基于海洋的药物发现所面临的一项重要挑战。Primmorph,一种三维细胞培养系统,可为从海洋海绵中生产抗癌药物的代谢物提供可持续来源。在本研究中,评估了Primmorph提取物以及[具体海绵种类1]、[具体海绵种类2]和[具体海绵种类3]海绵中胶层的抗癌活性。从细胞毒性、集落形成、细胞周期和凋亡方面研究了抗增殖活性。通过迁移试验和基质金属蛋白酶活性评估迁移情况。使用实时PCR分析增殖和迁移相关基因的表达。用[具体海绵种类1]、[具体海绵种类2]和[具体海绵种类3]的Primmorph提取物和中胶层处理可抑制HepG2细胞的迁移和增殖活性。尽管Primmorph提取物导致细胞周期停滞,但[具体海绵种类3]的中胶层未显示出任何抗癌活性。在所选择的海绵物种中,就抗增殖和抗迁移活性而言,[具体海绵种类2]的Primmorph提取物是最有前景的抗癌剂。此外,Primmorph提取物具有在明确且可控的条件下发挥作用的优势,这使得它作为生物反应器易于应用。