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Molecules
2019 Aug 29;2417:. doi: 10.3390/molecules24173154.
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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.
Malyarenko OS
,
Malyarenko TV
,
Kicha AA
,
Ivanchina NV
,
Ermakova SP
.
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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.
Figure 1. The structure of polar steroids isolated from starfish P. pectinifera.
Figure 2. The effect of polar steroids from P. pectinifera (1–3) and X-ray radiation on colony formation in human colorectal carcinoma cells. DLD-1 (A), HCT 116 (B), and HT-29 (C) cells (2.4 × 104) with or without polar steroid 1–3 (40 µM) or (D,E) X-ray radiation (2–10 Gy) treatment were subcultured onto 0.3% Basal Medium Eagle (BME) agar containing 10% FBS, 2 mM L-glutamine, and 25 µg/mL gentamicin. After 14 days of incubation, the number (A–D) and size (E) of the colonies were evaluated under a microscope with the aid of the ImageJ software program. All experiments were repeated at least three times in each group (n = 9 for control or compounds treated cells or X-ray exposed cells, n—quantity of photos). Results are expressed as the mean ± standard deviation (SD). The asterisk (*) indicates a significant decrease in the number or size of the colonies of cancer cells treated by polar steroids or X-ray compared to PBS-treated cells (*p < 0.05, **p < 0.01, ***p < 0.001).
Figure 3. The radiosensitizing effects of polar steroids from P. pectinifera (1–3) on colony formation in human colorectal carcinoma cells. DLD-1 (A,B), HCT 116 (C,D), and HT-29 (E,F) cells (2.4 × 104) were either treated or not treated with a combination of polar steroids 1–3 (1, 2, 4 µM) and X-ray radiation (2 Gy) and subcultured onto 0.3% Basal Medium Eagle (BME) agar containing 10% FBS, 2 mM L-glutamine, and 25 µg/mL gentamicin. After 14 days of incubation, the number (A,C,E) and size (B,D,F) of the colonies was evaluated under a microscope with the aid of the ImageJ software program. All experiments were repeated at least three times in each group (n = 9 for control or compounds treated cells or X-ray exposed cells, n—quantity of photos). The magnification of representative photos is 10×. Results are expressed as the mean ± standard deviation (SD). The asterisk (*) indicates a significant decrease in the number or size of colonies of cancer cells treated with X-ray compared to PBS-treated cells or polar steroids in combination with X-ray compared to irradiated cells (*p < 0.05, ***p < 0.001).
Figure 4. The effect of combinatorial treatment by asterosaponin P1 from P. pectinifera with radiation on apoptosis induction in HT-29 cells. (A) Regulation of the anti-apoptotic (Bcl-XL) and pro-apoptotic (Bax) proteins expression as well as the initiator (caspase 9) and effector (caspase 3, cleaved caspase 3) caspases, and b-actin by X-ray or with a combination of asterosaponin P1 and X-ray in HT-29 cells. (B) Relative bands density was measured using Image Lab™ Software 4.1. Quantitative results are presented as the mean values from three independent experiments. Significant differences were evaluated using the Student’s t-test. The asterisks (***p < 0.001) indicate a significant alteration of protein expression in cells treated by X-ray compared to PBS-treated cells, or asterosaponin P1 in combination with X-ray compared to irradiated cells. (C) HT-29 cells were either treated or not treated by X-ray (2 Gy) or with a combination of asterosaponin P1 (4 µM) and radiation (2 Gy). DNA comets were stained with ethidium bromide and visualized using a fluorescent microscope ZOE™ Fluorescent Cell Imager. Representative images (Scale bar = 100 µm).
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