Department of Biological Sciences, Faculty of Science, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Pharm Biol. 2013 Sep;51(9):1110-24. doi: 10.3109/13880209.2013.781194. Epub 2013 Jun 7.
For its variety of biological activities, Tamarix aucheriana (Decne.) Baum. (Tamaricaceae) has an extensive history as a traditional Arab medicine.
Antimitogenic and chemo-sensitizing activities of syringic acid (SA) were studied against human colorectal cancer.
Chromatographic and spectral data were used for the isolation and identification of SA. MTT, flow cytometry, in vitro invasion and angiogenesis assays, fluoremetry, ELISA and Real Time qPCR were used to test antimitogenic and chemo-sensitizing activities of SA, cell cycle, apoptosis, proteasome and NFκB-DNA-binding activities, cancer cell invasion and angiogenesis, and expression of cell cycle/apoptosis-related genes.
SA showed a time- and dose-dependent (IC₅₀ = 0.95-1.2 mg mL⁻¹) antimitogenic effect against cancer cells with little cytotoxicity on normal fibroblasts (≤20%). SA-altered cell cycle (S/G2-M or G1/G2-M phases) in a time-dependent manner, induced apoptosis, inhibited DNA-binding activity of NFκB (p ≤ 0.0001), chymotrypsin-like/PGPH (peptidyl-glutamyl peptide-hydrolyzing) (p ≤ 0.0001) and the trypsin-like (p ≤ 0.002) activities of 26S proteasome and angiogenesis. SA also differentially sensitized cancer cells to standard chemotherapies with a marked increase in their sensitivity to camptothecin (500-fold), 5FU (20,000-fold), doxorubicin (210-fold), taxol (3134-fold), vinblastine (1000-fold), vincristine (130-fold) and amsacrine (107-fold) compared to standard drugs alone.
SA exerted its chemotherapeutic and chemo-sensitizing effects through an array of mechanisms including cell-cycle arrest, apoptosis induction, inhibition of cell proliferation, cell migration, angiogenesis, NFκB DNA-binding and proteasome activities.
These results demonstrate the potential of SA as an antimitogenic and chemo-sensitizing agent for human colorectal cancer.
柽柳（柽柳科）因其多种生物活性，在阿拉伯传统医学中被广泛用作药物。
研究丁香酸（SA）对人结直肠癌细胞的抗有丝分裂和化疗增敏活性。
采用色谱和光谱数据对 SA 进行分离和鉴定。采用 MTT、流式细胞术、体外侵袭和血管生成试验、荧光计、ELISA 和实时 qPCR 检测 SA 的抗有丝分裂和化疗增敏活性、细胞周期、细胞凋亡、蛋白酶体和 NFκB-DNA 结合活性、癌细胞侵袭和血管生成以及细胞周期/凋亡相关基因的表达。
SA 对癌细胞表现出时间和剂量依赖性的抗有丝分裂作用（IC₅₀=0.95-1.2mg/ml），对正常成纤维细胞的细胞毒性较小（≤20%）。SA 以时间依赖性方式改变细胞周期（S/G2-M 或 G1/G2-M 期），诱导细胞凋亡，抑制 NFκB 的 DNA 结合活性（p≤0.0001），以及糜蛋白酶样/PGPH（肽基谷氨酰肽水解）（p≤0.0001）和 26S 蛋白酶体的胰蛋白酶样活性（p≤0.002）。SA 还使癌细胞对标准化疗药物的敏感性不同程度地增加，使它们对喜树碱（500 倍）、5FU（20000 倍）、阿霉素（210 倍）、紫杉醇（3134 倍）、长春碱（1000 倍）、长春新碱（130 倍）和安吖啶（107 倍）的敏感性显著增加。
SA 通过一系列机制发挥其化疗和化疗增敏作用，包括细胞周期停滞、细胞凋亡诱导、抑制细胞增殖、细胞迁移、血管生成、NFκB DNA 结合和蛋白酶体活性。
这些结果表明，SA 具有作为人结直肠癌细胞抗有丝分裂和化疗增敏剂的潜力。
