Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania.
MEDFUTURE - Research Center for Advanced Medicine, "Iuliu-Hatieganu" University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania.
Int J Mol Sci. 2019 Mar 9;20(5):1199. doi: 10.3390/ijms20051199.
Phytochemicals are natural compounds synthesized as secondary metabolites in plants and represent an important source of molecules with therapeutic applications. Attention is accorded to their potential in anti-cancer therapies as single agents or adjuvant treatment. Herby, we evaluated the in vitro effects of a panel of natural compounds with focus on caffeic acid phenethyl ester (CAPE) and Kaempferol for the treatment of human colon cancer.
We exposed two human colon cancer cell lines, RKO and HCT-116, followed by functional examination of cell viability, cell proliferation and invasion, cell cycle, apoptosis, and autophagy. Modifications in gene expression were investigated through microarray and detection of existing mutations and finding of new ones was done with the help of Next Generation Sequencing (NGS).
Both CAPE and Kaempferol inhibit cell proliferation, motility and invasion, and stimulate apoptosis and autophagy, concomitant with modifications in coding and noncoding genes' expression. Moreover, there are pathogenic mutations that are no longer found upon treatment with CAPE and Kaempferol.
Our findings indicate that CAPE and Kaempferol have the ability to negatively influence the development and advancement of colon cancer in vitro by specifically altering the cells at the molecular level; this activity can be exploited in possible adjuvant therapies once the optimal dose concentration with minimal side effects but with cancer inhibitory activity is set in vivo.
植物化学物质是植物作为次生代谢物合成的天然化合物,是具有治疗应用潜力的分子的重要来源。人们关注它们作为单一药物或辅助治疗在癌症治疗中的潜在作用。在本研究中,我们评估了一组天然化合物的体外效应,重点是咖啡酸苯乙酯(CAPE)和山柰酚对人类结肠癌的治疗作用。
我们暴露于两种人结肠癌细胞系,RKO 和 HCT-116,然后进行细胞活力、细胞增殖和侵袭、细胞周期、细胞凋亡和自噬的功能检测。通过微阵列研究基因表达的变化,并通过下一代测序(NGS)检测现有突变和寻找新突变。
CAPE 和山柰酚均可抑制细胞增殖、迁移和侵袭,并刺激细胞凋亡和自噬,同时伴有编码和非编码基因表达的改变。此外,在 CAPE 和山柰酚治疗后,不再发现致病性突变。
我们的研究结果表明,CAPE 和山柰酚通过特异性地在分子水平上改变细胞,具有在体外抑制结肠癌发展和进展的能力;一旦确定了体内具有最小副作用但具有抗癌活性的最佳剂量浓度,这种活性就可以在可能的辅助治疗中得到利用。