Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Int J Cancer. 2012 May 1;130(9):2176-84. doi: 10.1002/ijc.26251. Epub 2011 Sep 12.
Numerous cancer therapeutics were originally identified from natural products used in traditional medicine. One such agent is acetyl-11-keto-beta-boswellic acid (AKBA), derived from the gum resin of the Boswellia serrata known as Salai guggal or Indian frankincense. Traditionally, it has been used in Ayurvedic medicine to treat proinflammatory conditions. In this report, we hypothesized that AKBA can affect the growth and metastasis of colorectal cancer (CRC) in orthotopically implanted tumors in nude mice. We found that the oral administration of AKBA (50-200 mg/kg) dose-dependently inhibited the growth of CRC tumors in mice, resulting in decrease in tumor volumes than those seen in vehicle-treated mice without significant decreases in body weight. In addition, we observed that AKBA was highly effective in suppressing ascites and distant metastasis to the liver, lungs and spleen in orthotopically implanted tumors in nude mice. When examined for the mechanism, we found that markers of tumor proliferation index Ki-67 and the microvessel density cluster of differentiation (CD31) were significantly downregulated by AKBA treatment. We also found that AKBA significantly suppressed nuclear factor-κB (NF-κB) activation in the tumor tissue and expression of proinflammatory (cyclooxygenase-2), tumor survival (bcl-2, bcl-xL, inhibitor of apoptosis (IAP-1) and survivin), proliferative (cyclin D1), invasive (intercellular adhesion molecule 1 and matrix metalloproteinase-9) and angiogenic C-X-C (CXC) receptor 4 and vascular endothelial growth factor) biomarkers. When examined for serum and tissue levels of AKBA, a dose-dependent increase in the levels of the drug was detected, indicating its bioavailability. Thus, our findings suggest that this boswellic acid analog can inhibit the growth and metastasis of human CRC in vivo through downregulation of cancer-associated biomarkers.
许多癌症治疗药物最初是从传统医学中使用的天然产物中发现的。一种这样的药物是乙酰-11-酮-β-乳香酸（AKBA），它来自 Boswellia serrata 的树胶树脂，称为 Salai guggal 或印度乳香。传统上，它被用于阿育吠陀医学中治疗炎症性疾病。在本报告中，我们假设 AKBA 可以影响荷瘤裸鼠中结直肠癌（CRC）的生长和转移。我们发现，AKBA 的口服给药（50-200mg/kg）剂量依赖性地抑制了小鼠 CRC 肿瘤的生长，导致肿瘤体积减小，而体重无明显减轻。此外，我们观察到 AKBA 非常有效地抑制了荷瘤裸鼠原位肿瘤中的腹水和远处转移到肝脏、肺和脾脏。在检查机制时，我们发现 AKBA 处理显著下调了肿瘤增殖指数 Ki-67 和微血管密度分化簇（CD31）的标志物。我们还发现 AKBA 显著抑制了肿瘤组织中核因子-κB（NF-κB）的激活和促炎（环氧化酶-2）、肿瘤存活（bcl-2、bcl-xL、凋亡抑制剂（IAP-1）和生存素）、增殖（cyclin D1）、侵袭（细胞间粘附分子 1 和基质金属蛋白酶-9）和血管生成 C-X-C（CXC）受体 4 和血管内皮生长因子）生物标志物的表达。在检查 AKBA 的血清和组织水平时，检测到药物水平呈剂量依赖性增加，表明其生物利用度。因此，我们的研究结果表明，这种乳香酸类似物可以通过下调与癌症相关的生物标志物来抑制人 CRC 的体内生长和转移。
