Rahman Heshu Sulaiman, Rasedee Abdullah, How Chee Wun, Zeenathul Nazariah Allaudin, Chartrand Max Stanley, Yeap Swee Keong, Abdul Ahmad Bustamam, Tan Sheau Wei, Othman Hemn Hassan, Ajdari Zahra, Namvar Farideh, Arulselvan Palanisamy, Fakurazi Sharida, Mehrbod Parvaneh, Daneshvar Nasibeh, Begum Hasina
Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia ; Faculty of Veterinary Medicine, University of Sulaimany, Sulaimany City, Northern Iraq.
Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia ; Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.
Int J Nanomedicine. 2015 Mar 2;10:1649-66. doi: 10.2147/IJN.S67113. eCollection 2015.
Cancer nanotherapy is progressing rapidly with the introduction of many innovative drug delivery systems to replace conventional therapy. Although the antitumor activity of zerumbone (ZER) has been reported, there has been no information available on the effect of ZER-loaded nanostructured lipid carrier (NLC) (ZER-NLC) on murine leukemia cells. In this study, the in vitro and in vivo effects of ZER-NLC on murine leukemia induced with WEHI-3B cells were investigated. The results from 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, Hoechst 33342, Annexin V, cell cycle, and caspase activity assays showed that the growth of leukemia cells in vitro was inhibited by ZER-NLC. In addition, outcomes of histopathology, transmission electron microscopy, and Tdt-mediated dUTP nick-end labeling analyses revealed that the number of leukemia cells in the spleen of BALB/c leukemia mice significantly decreased after 4 weeks of oral treatment with various doses of ZER-NLC. Western blotting and reverse-transcription quantitative polymerase chain reaction assays confirmed the antileukemia effects of ZER-NLC. In conclusion, ZER-NLC was shown to induce a mitochondrial-dependent apoptotic pathway in murine leukemia. Loading of ZER in NLC did not compromise the anticancer effect of the compound, suggesting ZER-NLC as a promising and effective delivery system for treatment of cancers.
随着许多创新药物递送系统的引入以取代传统疗法，癌症纳米疗法正在迅速发展。尽管已报道了零陵香酮（ZER）的抗肿瘤活性，但关于负载ZER的纳米结构脂质载体（NLC）（ZER-NLC）对小鼠白血病细胞的作用尚无可用信息。在本研究中，研究了ZER-NLC对由WEHI-3B细胞诱导的小鼠白血病的体外和体内作用。3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐、Hoechst 33342、膜联蛋白V、细胞周期和半胱天冬酶活性测定的结果表明，ZER-NLC可抑制白血病细胞的体外生长。此外，组织病理学、透射电子显微镜和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记分析的结果显示，用不同剂量的ZER-NLC口服治疗4周后，BALB/c白血病小鼠脾脏中的白血病细胞数量显著减少。蛋白质免疫印迹和逆转录定量聚合酶链反应测定证实了ZER-NLC的抗白血病作用。总之，ZER-NLC被证明可在小鼠白血病中诱导线粒体依赖性凋亡途径。将ZER负载于NLC中并未损害该化合物的抗癌效果，这表明ZER-NLC是一种有前景且有效的癌症治疗递送系统。
