Delgado-Roche Livan, González Kethia, Mesta Fernando, Couder Beatriz, Tavarez Zaira, Zavala Ruby, Hernandez Ivones, Garrido Gabino, Rodeiro Idania, Vanden Berghe Wim
Dirección Médica, Laboratorios Liomont S.A. de C.V., Ciudad de México, México.
Instituto de Ciencias del Mar (ICIMAR), La Habana, Cuba.
Front Pharmacol. 2020 Nov 30;11:592985. doi: 10.3389/fphar.2020.592985. eCollection 2020.
Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase ( < 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity of metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a polar extract in a xenograft mice model. These results suggest the potential use of marine plant metabolites as adjuvant treatment in cancer therapy.
海洋植物是具有药理活性代谢物的重要来源。本研究的目的是评估从海洋植物中获得的多酚组分和海石竹素B对人结肠癌细胞的细胞毒性和抗肿瘤活性。通过结晶紫测定法，用受试产品处理包括HCT15、HCT116、SW260和HT29在内的人癌细胞系，以评估细胞毒性。在HCT15细胞中于48小时使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶通过流式细胞术评估这些天然产物的潜在促凋亡作用。此外，使用2',7'-二氯二氢荧光素二乙酸酯染色通过荧光测量活性氧(ROS)的生成，并通过分光光度法测量巯基浓度。在无胸腺裸鼠异种移植模型中评估多酚组分(25mg/kg)的抗肿瘤活性。还使用抗半胱天冬酶3和抗Bcl-2抗体通过免疫组织化学评估促凋亡作用。结果表明，受试产品具有结肠癌细胞细胞毒性。此外，受试产品导致HCT15细胞内ROS生成显著增加(P<0.05)，以及巯基浓度降低。多酚组分在异种移植小鼠模型中抑制肿瘤生长并诱导凋亡。这些结果证明了相关代谢物的细胞毒性活性，至少与ROS过量产生和促凋亡作用有关。在此，我们首次证明了极性提取物在异种移植小鼠模型中的抗肿瘤活性。这些结果表明海洋植物代谢物在癌症治疗中作为辅助治疗的潜在用途。
