Nassir Anmar M, Shahzad Naiyer, Ibrahim Ibrahim A A, Ahmad Iqbal, Md Shadab, Ain Mohammad R
Department of Surgery, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Saudi Pharm J. 2018 Sep;26(6):876-885. doi: 10.1016/j.jsps.2018.03.009. Epub 2018 Mar 15.
Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC and IC) of 15.6 ± 1.49 and 41.1 ± 2.19 μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.
白藜芦醇(RL)是一种天然多酚,以其对多种人类癌细胞系的多种生物学作用而闻名。但其低水溶性、低生物利用度和稳定性限制了其对前列腺癌的疗效。在本研究中,设计了包裹白藜芦醇的聚合物纳米颗粒(RLPLGA),并测定了其对前列腺癌细胞系(LNCaP)的细胞毒性和凋亡细胞死亡模式。通过溶剂置换法制备纳米颗粒,并对其粒径、透射电子显微镜(TEM)、包封率、差示扫描量热法(DSC)和药物释放进行研究。RLPLGA对LNCaP细胞的细胞活力显著降低,其50%和90%抑制浓度(IC50和IC90)分别为15.6±1.49和41.1±2.19μM。这种作用是由细胞凋亡介导的,LNCaP细胞在G1-S转换期的细胞周期停滞、磷脂酰丝氨酸外化、DNA断裂、线粒体膜电位丧失和活性氧生成均证实了这一点。此外,在所有测试浓度下,与游离RL相比,纳米颗粒对LNCaP细胞的细胞毒性显著更高。即使在200μM时,RLPLGA纳米颗粒对小鼠巨噬细胞也没有不良细胞毒性作用。我们的研究结果支持所开发的负载白藜芦醇的纳米颗粒在前列腺癌化学预防/化疗中的潜在应用,且对正常细胞无不良影响。