Purkayastha Sudarshana, Berliner Alexandra, Fernando Suraj Shawn, Ranasinghe Buddima, Ray Indrani, Tariq Hussnain, Banerjee Probal
Department of Chemistry, The College of Staten Island (CUNY), Staten Island, NY 10314, USA.
Brain Res. 2009 Apr 17;1266:130-8. doi: 10.1016/j.brainres.2009.01.066. Epub 2009 Feb 11.
Turmeric, an essential ingredient of culinary preparations of Southeast Asia, contains a major polyphenolic compound, named curcumin or diferuloylmethane, which eliminates cancer cells derived from a variety of peripheral tissues. Although in vitro experiments have addressed its anti-tumor property, no in vivo studies have explored its anti-cancer activity in the brain. Oral delivery of this food component has been less effective because of its low solubility in water.We show that a soluble formulation of curcumin crosses the blood–brain barrier but does not suppress normal brain cell viability. Furthermore, tail vein injection, or more effectively, intracerebral injection through a cannula, blocks brain tumor formation in mice that had already received an intracerebral bolus of mouse melanoma cells (B16F10).While exploring the mechanism of its action in vitro we observed that the solubilized curcumin causes activation of proapoptotic enzymes caspase 3/7 in human oligodendroglioma (HOG) and lung carcinoma (A549) cells, and mouse tumor cells N18(neuroblastoma), GL261 (glioma), and B16F10. A simultaneous decrease in cell viability is also revealed by MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide]assays. Further examination of the B16F10 cells showed that curcumin effectively suppresses Cyclin D1, P-NF-kB, BclXL, P-Akt, and VEGF, which explains its efficacy in blocking proliferation, survival, and invasion of the B16F10 cells in the brain. Taken together,solubilized curcumin effectively blocks brain tumor formation and also eliminates brain tumor cells. Therefore, judicious application of such injectable formulations of curcumin could be developed into a safe therapeutic strategy for treating brain tumors.
姜黄是东南亚烹饪调料中的重要成分，含有一种主要的多酚化合物，名为姜黄素或二阿魏酰甲烷，它能消除源自多种外周组织的癌细胞。尽管体外实验已经研究了其抗肿瘤特性，但尚无体内研究探索其在脑内的抗癌活性。由于这种食物成分在水中的溶解度低，口服给药效果较差。我们发现，姜黄素的一种可溶性制剂能够穿过血脑屏障，但不会抑制正常脑细胞的活力。此外，尾静脉注射，或者更有效的是通过套管进行脑内注射，能够阻止已经接受脑内注射小鼠黑色素瘤细胞（B16F10）的小鼠形成脑肿瘤。在体外探索其作用机制时，我们观察到，溶解的姜黄素会导致人少突胶质细胞瘤（HOG）、肺癌（A549）细胞以及小鼠肿瘤细胞N18（神经母细胞瘤）、GL261（胶质瘤）和B16F10中的促凋亡酶半胱天冬酶3/7激活。MTT [3-(4, 5-二甲基噻唑-2)-2, 5-二苯基四氮唑溴盐] 检测也显示细胞活力同时下降。对B16F10细胞的进一步检测表明，姜黄素能有效抑制细胞周期蛋白D1、磷酸化核因子-κB、BclXL、磷酸化蛋白激酶B和血管内皮生长因子，这解释了其在阻止B16F10细胞在脑内增殖、存活和侵袭方面的功效。综上所述，溶解的姜黄素能有效阻止脑肿瘤形成，还能消除脑肿瘤细胞。因此，明智地应用这种可注射的姜黄素制剂有望发展成为一种治疗脑肿瘤的安全治疗策略。
