Abstract
Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm Thalassia testudinum (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model. MTT assays revealed a dose-dependent decrease of cell viability of RKO, CT26, and SW480 cells upon TTE treatment with IC50 values of, respectively, 175, 115, and 60 μg/mL. Furthermore, TTE significantly prevented basal and bFGF-induced angiogenesis in the chicken chorioallantoic membrane angiogenesis assay. In addition, TTE suppressed bFGF-induced migration of endothelial cells in a wound closure assay. Finally, TTE treatment abrogated CT26 colorectal cancer growth and increased overall organism survival in a syngeneic murine allograft model. Corresponding transcriptome profiling and pathway analysis allowed for the identification of the mechanism of action for the antitumor effects of TTE. In line with our in vitro/in vivo results, TTE treatment triggers ATF4-P53-NFκB specific gene expression and autophagy stress pathways. This results in suppression of colon cancer cell growth, cell motility, and angiogenesis pathways in vitro and in addition promotes antitumor immunogenic cell death in vivo.
Highlights
Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignancies and a leading cause of cancer death worldwide [1]
Our results show the cytotoxic activity of the polyphenolic fraction of Thalassia testudinum (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
Tumor cell cytotoxic effects of TTE were assessed by MTT viability assays in human RKO, SW480, and mouse CT26 colon cancer cells, in a concentration range of 1 to
Summary
Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignancies and a leading cause of cancer death worldwide [1]. The last Cuban Health Report indicated that CRC is the third cause of mortality and its incidence ranked fifth, among all cancers [2]. The treatments fail due to drug resistance, tumor relapse, and/or high adverse toxicity. It is an urgent need for the development of new anticancer drugs. There is a renewed interest in plant phytochemicals for cancer treatment [3]. The public World Health Organization (WHO) global report on traditional and complementary medicine indicates that in developing countries, 80% of people rely on plant-derived medicines for health care [4]. Besides traditional medicinal plants, marine floras have become a source of bioactive phytochemicals with antioxidant, immunomodulatory, and antitumor activities [5,6]
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