Effects of Polar Steroids from the Starfish Patiria (=Asterina) pectinifera in Combination with X-Ray Radiation on Colony Formation and Apoptosis Induction of Human Colorectal Carcinoma Cells.

Olesya S Malyarenko,Alla A Kicha,Timofey V Malyarenko,Svetlana P Ermakova,Natalia V Ivanchina

doi:10.3390/molecules24173154

Abstract

Despite significant advances in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Chemoradiation therapy is a rational approach that has already proven beneficial for several malignancies. However, the existence of toxicity to normal tissue is a serious limitation of this treatment modality. The aim of the present study is to investigate the ability of polar steroids from starfish Patiria (=Asterina) pectinifera to enhance the efficacy of radiation therapy in colorectal carcinoma cells. The cytotoxic activity of polar steroids and X-ray radiation against DLD-1, HCT 116, and HT-29 cells was determined by an MTS assay. The effect of compounds, X-ray, and their combination on colony formation was studied using the soft agar method. The molecular mechanism of the radiosensitizing activity of asterosaponin P1 was elucidated by western blotting and the DNA comet assay. Polar steroids inhibited colony formation in the tested cells, and to a greater extent in HT-29 cells. Asterosaponin P1 enhanced the efficacy of radiation and, as a result, reduced the number and size of the colonies of colorectal cancer cells. The radiosensitizing activity of asterosaponin P1 was realized by apoptosis induction through the regulation of anti- and pro-apoptotic protein expression followed by caspase activation and DNA degradation.

Highlights

Colorectal carcinoma is the third most common cancer in men and the second in women
The aim of the present study is to investigate the ability of polar steroids from starfish Patiria (=Asterina) pectinifera to enhance the efficacy of radiation therapy in colorectal carcinoma cells
It was reported that polyhydroxysteroids and steroidal glycosides from starfishes possess moderate cytotoxic activity against human cancer cell lines [17,18,19]

Summary

Introduction

Colorectal carcinoma is the third most common cancer in men and the second in women. Radiation therapy using high-energy rays (such as X-ray) is the method most often used to destroy rectal cancer cells. Surgery, chemotherapy, immunotherapy, and the combinatorial treatment by chemo- and radiation therapy, called chemoradiation therapy, are the most effective curative modalities for people with colorectal cancer [2]. The short- and long-term side effects of high doses of radiation exposure, as well as widely used chemotherapeutic drugs (5-Fluorouracil, Capecitabine, Oxaliplatin, and Trifluridine), are encouraging scientists to develop more effective schemes for cancer therapy [3]. The selective sensitization of cancer cells by natural, non-toxic compounds to low doses of ionizing radiation is a novel approach for improving cancer treatment

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