Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model

Abstract

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 Thalassia testudinum 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 in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo 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 (p < 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 T. testudinum metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a T. testudinum polar extract in a xenograft mice model. These results suggest the potential use of T. testudinum marine plant metabolites as adjuvant treatment in cancer therapy.

Marine Seagrass Extract of Thalassia testudinum Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways

“…In the present study, we applied transcriptome profiling and systems biology approaches to further characterize in vitro/in vivo antitumor activities of a standardized hydroethanolic extract from leaves of the marine angiosperm Thalassia testudinum growing on the coasts of Cuba [ 9 , 10 ]. In line with our previous results, time- and dose-dependent loss of cell viability was observed in the colon cancer cell lines (RKO, SW480, and CT26), whereas non-tumor cells remained unaffected [ 15 , 16 ]. Among all tested colon cancer cell types, SW480 was identified as the most sensitive to TTE treatment with IC 50 values of 60 µg/mL.…”

“…To date, various anticancer flavonoids have been identified in TTE, such as apigenin, luteolin, chrysoeriol-7- O -β-D-glucopyranoside, and thalassiolin B [ 9 , 12 , 13 , 16 , 32 , 33 , 34 ]. Similar to TTE, apigenin treatment of SW480 cells shows comparable cell cytotoxicity (IC 50 value 40 µM) [ 35 , 36 ].…”

“…In addition, chrysoeriol-7- O -β-D-glucopyranoside and luteolin were found to be effective antitumor bioactive molecules against colon cancer cells [ 37 ]. Recently, we showed that thalassiolin B and the polyphenolic fraction isolated from TTE both mimicked induced ROS production and tumor regression in a xenograft colorectal cancer model [ 16 ]. Accordingly, antitumor efficacy of TTE could be attributed to the presence of thalassiolin B, apigenin, chrysoeriol-7- O -β-D-glucopyranoside, and luteolin in this mixture [ 16 , 35 , 36 , 37 , 38 ].…”

“…For apigenin, luteolin, and chrysoeriol, immunogenic and autophagy-promoting properties have already been reported ( Supplementary Table S6 ) [ 32 , 33 , 38 , 39 , 59 ]. In addition, we previously found that treatment with another purified TTE constituent (Thalassiolin B) fully mimicked ROS production and tumor regression by polyphenolic fraction treatment in a xenograft colorectal cancer model [ 16 ]. Thus, the antitumor efficacy of TTE could be attributed to the presence of multiple bioactive compounds, which exhibit a broad spectrum of therapeutic properties in vitro/in vivo.…”

“…Taken together, our results show the cytotoxic activity of the polyphenolic fraction of TTE and the thalassiolin B, which it is associated with reactive oxygen species (ROS) generation and pro-apoptotic effects in HCT15, a human colorectal cancer cell line. Furthermore, the antitumor activity of the polyphenolic fraction was demonstrated in a xenograft mice model [ 16 ], suggesting that this marine plant holds promise as a rich natural resource of antitumor phytochemicals.…”