Abstract
Colorectal cancer is one of the most frequent types of malignancy in the world. The search for new approaches of increasing the efficacy of cancer therapy is relevant. This work was aimed to study individual, combined anticancer effects, and molecular mechanism of action of sulfated laminaran AaLs of the brown alga Alaria angusta and protolinckiosides A (PL1), B (PL2), and linckoside L1 (L1) of the starfish Protoreaster lincki using a 3D cell culture model. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), soft agar, 3D spheroids invasion, and Western blotting assays were performed to determine the effect and mechanism of the action of investigated compounds or their combinations on proliferation, colony formation, and the invasion of 3D HCT 116 spheroids. AaLs, PL1, PL2, and L1 individually inhibited viability, colony growth, and the invasion of 3D HCT 116 spheroids in a variable degree with greater activity of linckoside L1. AaLs in combination with L1 exerted synergism of a combined anticancer effect through the inactivation of protein kinase B (AKT) kinase and, consequently, the induction of apoptosis via the regulation of proapoptotic/antiapoptotic proteins balance. The obtained data about the efficacy of the combined anticancer effect of a laminaran derivative of brown algae and polyhydroxysteroid glycosides of starfish open up prospects for the development of new therapeutic approaches for colorectal cancer treatment.
Highlights
Oncological diseases are one of the main causes of human mortality in the modern world, and the economic and financial burden for cancer research is increasing [1]
Modification of Laminaran from A. angusta, and Structural Characteristics of Laminaran from the brown alga A. angusta was isolated according to a modified method described in recent work [22]
The extraction was performed with 0.1 N hydrochloric acid at 60 ◦ C for 2 h, dialyzed, concentrated, precipitated with four volumes of 96% ethanol, and air-dried in order to obtain crude fractions of watersoluble polysaccharides
Summary
Oncological diseases are one of the main causes of human mortality in the modern world, and the economic and financial burden for cancer research is increasing [1]. Colorectal cancer is the most frequently diagnosed malignant cancer around the world, and one of the most common causes of death among cancer patients [2]. Many radically operated on patients experience dissemination of the process at different periods after the operation, and the overall 5-year survival rate of patients with metastatic colon cancer does not exceed 7–8% [4]. Despite the noticeable progress in the treatment of colorectal cancer using cytotoxic and targeted drugs, the effectiveness of chemotherapy for this type of cancer cannot be considered satisfactory, which dictates the need to search for new approaches in the treatment of patients with advanced colorectal cancer [5]. The combination of two or more therapeutic treatments regulating
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