Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore 721 102, West Bengal, India.
Bioorg Chem. 2015 Dec;63:85-100. doi: 10.1016/j.bioorg.2015.09.006. Epub 2015 Sep 30.
The main complication in betulinic acid (BA) based drug delivery has been observed due to its bulk structure. The present study demonstrates the potential effects of self assembled nano size betulinic acid (SA-BA) by treating human leukemic cell lines (KG-1A and K562) and its normal counterpart. Self assembly property of BA was investigated using SEM and DLS study which showed that the BA forms fibrous structure having few nanometers in diameter. Selective anti-leukemic efficacy study of SA-BA was investigated by cell viability assay. Mode of leukemic cell death and probable pathway of apoptosis was monitored by measuring ROS level, pro and anti-inflammatory cytokine status and expression of caspase-8 and caspage-3 by immunocytochemistry. Higher efficacy of SA-BA over non-assemble BA was monitored toward cancer cells, with no relevant toxicity to normal blood cells. SA-BA facilitated reactive oxygen species (ROS) mediated leukemic cell death, confirmed by pre-treatment of N-acetyl-L-cysteine. Induction of apoptosis by SA-BA treatment increased pro-inflammatory cytokines, specifically potentiated TNF-α mediated cell death, confirmed by expression of caspase-8 and caspage-3 by immunocytochemistry. This study explored the better anti-leukemic efficacy of SA-BA over BA and this modification will enrich the use of BA in cancer therapy.
桦木酸（BA）的主要给药并发症是由于其体积庞大。本研究通过治疗人白血病细胞系（KG-1A 和 K562）及其正常对照，展示了自组装纳米桦木酸（SA-BA）的潜在作用。通过 SEM 和 DLS 研究研究了 BA 的自组装特性，结果表明 BA 形成具有几纳米直径的纤维状结构。通过细胞活力测定法研究了 SA-BA 的选择性抗白血病功效。通过测量 ROS 水平、促炎和抗炎细胞因子状态以及通过免疫细胞化学测定 caspase-8 和 caspase-3 的表达，监测白血病细胞死亡的模式和可能的凋亡途径。与非组装 BA 相比，SA-BA 对癌细胞的疗效更高，而对正常血细胞没有相关毒性。SA-BA 通过诱导活性氧（ROS）介导的白血病细胞死亡，通过 N-乙酰-L-半胱氨酸预处理得到证实。SA-BA 处理诱导的细胞凋亡增加了促炎细胞因子，特别是增强了 TNF-α 介导的细胞死亡，通过免疫细胞化学测定 caspase-8 和 caspase-3 的表达得到证实。本研究探索了 SA-BA 比 BA 更好的抗白血病功效，这种修饰将丰富 BA 在癌症治疗中的应用。
