Inoue Kanako, Kulsum Umme, Chowdhury Shahead Ali, Fujisawa Sei-Ichiro, Ishihara Mariko, Yokoe Ichiro, Sakagami Hiroshi
Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan.
Anticancer Res. 2005 Nov-Dec;25(6B):4053-9.
Berberine iodide (IK-1) and acetoneberberine (IK-2) showed higher cytotoxicity against five human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4, NA, CA9-22) and one human promyelocytic leukemia (HL-60) cell lines, than against normal human oral tissue-derived cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), producing a tumor specificity index of 4.0 and 3.6, respectively. IK-1 was more potent than IK-2 in inducing the production of apoptotic cells, internucleosomal DNA fragmentation, the activation of caspases-3, -8 and -9, and the increased expression of proapoptotic BAD protein, with a corresponding decrease in the expression of anti-apoptotic Bcl-2 protein in HL-60 cells. These compounds did not induce internucleosomal DNA fragmentation (only producing larger DNA fragment), nor increased the Bad protein expression in HSC-2 cells. The present study demonstrated the tumor-specific cytotoxicity and apoptosis-inducing activity of berberines, suggesting their possible antitumor potentiaL
碘化小檗碱（IK-1）和丙酮小檗碱（IK-2）对五种人类口腔鳞状细胞癌（HSC-2、HSC-3、HSC-4、NA、CA9-22）和一种人类早幼粒细胞白血病（HL-60）细胞系的细胞毒性，高于对正常人类口腔组织来源细胞（牙龈成纤维细胞HGF、牙髓细胞HPC、牙周膜成纤维细胞HPLF）的细胞毒性，其肿瘤特异性指数分别为4.0和3.6。在诱导HL-60细胞凋亡细胞产生、核小体间DNA片段化、半胱天冬酶-3、-8和-9的激活以及促凋亡BAD蛋白表达增加方面，IK-1比IK-2更有效，同时抗凋亡Bcl-2蛋白的表达相应降低。这些化合物在HSC-2细胞中未诱导核小体间DNA片段化（仅产生较大的DNA片段），也未增加Bad蛋白表达。本研究证明了小檗碱的肿瘤特异性细胞毒性和诱导凋亡活性，表明它们可能具有抗肿瘤潜力。
