Ranjbarnejad Tayebeh, Saidijam Massoud, Moradkhani Shirin, Najafi Rezvan
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Depatment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.
Prostaglandins Other Lipid Mediat. 2017 Jul;131:1-8. doi: 10.1016/j.prostaglandins.2017.05.003. Epub 2017 May 24.
Colorectal cancer (CRC) is the most common cancer. A proper method to reduce mortality of CRC is chemoprevention to prevent initiation and promotion of intestinal tumorgenesis. One of the promising and developing chemopreventive agents is natural compounds found in plants. Frankincense, the resin extract from the Boswellia specious, has been used in traditional and modern medicine for treating various diseases with very minimal side effects. In the current study, we investigated the anti-cancer activity of methanolic extract of Boswellia serrata (B. serrata) on HT-29 human colon cancer cells.
HT-29 cells were treated with different concentrations of B. serrata and cell viability was assessed by MTT assay. mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), MMP-9 and hypoxia-inducible factor-1 (HIF-1) were examined by quantitative real-time PCR. Apoptosis was evaluated by the proportion of sub-G1 cells. Prostaglandin E2 (PGE2) level and caspase 3 activity were determined by ELISA assay. Tube formation potential and HT-29 cells migration were assessed using three-dimensional vessel formation assay and scratch test.
B. serrata extract considerably decreased the expression of mPGES-1, VEGF, CXCR4, MMP-2, MMP-9 and HIF-1. The caspase 3 activity and percent of cells in sub-G1 phase were increased by B. serrata extract. Cell viability, PGE2 generation, in vitro tube formation and cell migration were decreased significantly in B. serrata-treated HT-29 compared to the control group.
Our findings suggest that B. serrata extract inhibits proliferation, angiogenesis and migration and induces apoptosis in HT-29 cells by inhibiting of mPGES-1 and decreasing the PGE2 level and its downstream targets.
结直肠癌（CRC）是最常见的癌症。降低CRC死亡率的一种合适方法是化学预防，以防止肠道肿瘤发生的起始和促进。有前景且正在发展的化学预防剂之一是植物中发现的天然化合物。乳香，即乳香树的树脂提取物，已被用于传统医学和现代医学来治疗各种疾病，且副作用极小。在本研究中，我们调查了锯叶乳香（B. serrata）甲醇提取物对HT-29人结肠癌细胞的抗癌活性。
用不同浓度的B. serrata处理HT-29细胞，并通过MTT法评估细胞活力。通过定量实时PCR检测微粒体前列腺素E合酶-1（mPGES-1）、血管内皮生长因子（VEGF）、C-X-C趋化因子受体4（CXCR4）、基质金属蛋白酶-2（MMP-2）、MMP-9和缺氧诱导因子-1（HIF-1）的mRNA表达。通过亚G1期细胞比例评估细胞凋亡。通过ELISA法测定前列腺素E2（PGE2）水平和半胱天冬酶3活性。使用三维血管形成试验和划痕试验评估血管生成潜力和HT-29细胞迁移。
B. serrata提取物显著降低了mPGES-1、VEGF、CXCR4、MMP-2、MMP-9和HIF-1的表达。B. serrata提取物增加了半胱天冬酶3活性和亚G1期细胞百分比。与对照组相比，B. serrata处理的HT-29细胞的细胞活力、PGE2生成、体外血管生成和细胞迁移显著降低。
我们的研究结果表明，B. serrata提取物通过抑制mPGES-1并降低PGE2水平及其下游靶点，抑制HT-29细胞的增殖、血管生成和迁移，并诱导细胞凋亡。
