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纳米封装叶绿酸通过激活线粒体信号级联和药物-DNA 相互作用,显著延缓体外和体内肺癌模型的进展。

Nano-encapsulated chlorophyllin significantly delays progression of lung cancer both in in vitro and in vivo models through activation of mitochondrial signaling cascades and drug-DNA interaction.

机构信息

Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, India.

School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India; Department of Zoology, Dum Dum Motijheel College, Kolkata-700074, India.

出版信息

Environ Toxicol Pharmacol. 2016 Sep;46:147-157. doi: 10.1016/j.etap.2016.07.006. Epub 2016 Jul 18.

DOI:10.1016/j.etap.2016.07.006
PMID:27458703
Abstract

Chlorophyllin (CHL), a sodium-copper-salt derived from chlorophyll, has been widely used as a food-dye, also reportedly having some anti-cancer effect. We tested if PLGA-loaded CHL (NCHL) could have additional protective abilities through its faster and targeted drug delivery in cancer cells. Physico-chemical characterization of NCHL was done through atomic-force microscopy and UV-spectroscopy. NCHL demonstrated greater ability of drug uptake and strong anti-cancer potentials in non-small cell lung cancer cells, A549, as revealed from data of% cell viability, generation of reactive-oxygen-species and expression of bax, bcl2, caspase3, p53 and cytochrome c proteins. Circular dichroic spectral data indicated strong binding of NCHL with calf-thymus-DNA, causing a conformational/structural change in DNA. Further, NCHL could cross the blood-brain-barrier in mice and showed greater efficacy in recovery process of tissue damage, reduction in chromosomal aberrations and% of micronuclei in co-mutagens (Sodiumarsenite+Benzo[a]Pyrene)-treated mice at a much reduced dose, indicating its use in therapeutic oncology.

摘要

叶绿酸铜钠(CHL)是叶绿素的钠盐,被广泛用作食用色素,据报道还具有一定的抗癌作用。我们测试了载有 PLGA 的 CHL(NCHL)是否可以通过更快、更靶向的癌细胞药物输送来提供额外的保护能力。通过原子力显微镜和紫外光谱对 NCHL 的理化性质进行了表征。NCHL 在非小细胞肺癌细胞 A549 中表现出更强的药物摄取能力和强大的抗癌潜力,这从细胞活力百分比、活性氧生成和 bax、bcl2、caspase3、p53 和细胞色素 c 蛋白表达的数据中可以看出。圆二色光谱数据表明 NCHL 与小牛胸腺 DNA 具有强烈的结合能力,导致 DNA 的构象/结构发生变化。此外,NCHL 可以穿过血脑屏障,在老鼠中显示出更大的疗效,在减少染色体畸变和共诱变剂(亚砷酸钠+苯并[a]芘)处理的老鼠中的微核百分比方面,在降低剂量的情况下,在组织损伤的恢复过程中表现出更大的疗效,表明其在肿瘤治疗学中的应用。

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