Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, PU, 61029, Italy.
Eur J Nutr. 2018 Jun;57(4):1381-1395. doi: 10.1007/s00394-017-1418-y. Epub 2017 Mar 10.
CaCo-2 colon cancer cells and HepG2 liver cancer cells represent two malignant cell lines, which show a high resistance to apoptosis induced by the conventional anticancer drugs. Vitexin-2-O-xyloside (XVX) and avenanthramides (AVNs) are naturally occurring dietary agents from Beta vulgaris var. cicla L. and Avena sativa L., respectively. The aim of this work was to evaluate the antiproliferative effects and the reduction of the pro-survival mechanisms exerted by XVX and AVNs, used individually and in combination, in CaCo-2 and HepG2 cancer cells.
XVX and AVNs were isolated by liquid chromatography and characterized by HPLC-PDA-MS. The XVX and AVN antiproliferative effects were evaluated through sulforhodamine B method, while their pro-apoptotic effects through caspase activity assays. RTqPCR was used to investigate the modulation of the pro-survival factors baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5), hypoxia inducible factor 1 A (HIF1A), and vascular endothelial growth factor A (VEGFA). Cellular antioxidant activity (CAA) was investigated by means of DCFH-DA assay, whereas chemical antioxidant capacity was evaluated by the ORAC method.
XVX and AVNs, both individually and in combination, inhibited the proliferation of CaCo-2 and HepG2 cancer cells, through activation of caspases 9, 8, and 3. XVX and AVNs downregulated the pro-survival genes BIRC5, HIF1A, and VEGFA. The CAA assay showed that AVNs exhibited strong antioxidant activity inside both CaCo-2 and HepG2 cells.
The antiproliferative activity of the XVX + AVNs mixture represents an innovative treatment, which is effective against two types of cancer cells characterized by high resistance to the conventional anticancer drugs.
CaCo-2 结肠癌细胞和 HepG2 肝癌细胞代表两种恶性细胞系，它们对常规抗癌药物诱导的细胞凋亡表现出高度抗性。牡荆素-2-O-木糖苷（XVX）和燕麦蒽酰胺（AVNs）分别是来自普通甜菜变种 cicla L. 和燕麦的天然存在的膳食剂。本工作的目的是评估 XVX 和 AVNs 的抗增殖作用以及降低它们单独和联合使用时对 CaCo-2 和 HepG2 癌细胞中促生存机制的影响。
通过液相色谱法分离 XVX 和 AVNs，并通过 HPLC-PDA-MS 进行表征。通过磺酰罗丹明 B 法评估 XVX 和 AVN 的抗增殖作用，通过半胱天冬酶活性测定评估其促凋亡作用。通过 RTqPCR 研究促生存因子杆状病毒凋亡抑制剂重复包含 5（BIRC5）、缺氧诱导因子 1A（HIF1A）和血管内皮生长因子 A（VEGFA）的调节。通过 DCFH-DA 测定法研究细胞抗氧化活性（CAA），通过 ORAC 法评估化学抗氧化能力。
XVX 和 AVNs 单独或联合使用均抑制 CaCo-2 和 HepG2 癌细胞的增殖，通过激活半胱天冬酶 9、8 和 3。XVX 和 AVNs 下调促生存基因 BIRC5、HIF1A 和 VEGFA。CAA 测定法表明，AVNs 在 CaCo-2 和 HepG2 细胞内均表现出很强的抗氧化活性。
XVX+AVNs 混合物的抗增殖活性代表了一种创新的治疗方法，对两种对常规抗癌药物具有高度抗性的癌症细胞有效。
