Abstract B12: Effect of Ganoderma lucidum on DNA damage and DNA repair in colorectal cancer cell lines

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Abstract Colorectal carcinoma (CRC) is the third most common type of cancer in the world and second most common cause of cancer related deaths in Europe. Countries of Central Europe (Czech Republic, Slovakia and Hungary) have one of the highest rates both for incidence and mortality of CRC and this disease therefore possesses a serious health, social and economic problem. CRC is a complex disease that develops as consequence of environmental and health risk factors with particular involvement of suboptimal DNA repair, resulting in accumulation of DNA damage. Reactive oxygen species (ROS) represent a group of highly reactive molecules tightly controlled by cellular antioxidant system. Disturbance of the prooxidation–antioxidation homeostasis can lead to ROS accumulation and consequently to DNA damage and apoptosis. Many natural compounds possess anti-cancer activities with the generation of ROS. Cancer cells are more sensitive to oxidative DNA damage than non-malignant cells. Modulation of oxidative DNA damage and DNA repair pathways by natural compounds may lead to selective cancer cell-death and to sensitization of cancer cells to treatment. Ganoderma Lucidum (GLC) (Reishi, Ling-Zhi) is a mushroom used in Chinese medicine for thousands of years for prevention or therapy of many different disorders including cancer. The aim of our study is to define the effect of Ganoderma lucidum (GLC) extract on DNA damage and DNA repair machinery in colorectal cancer cell lines (HTC116, HCT116p53-/-, HT29, SW480). Our results showed that 6hrs GLC treatment in colorectal cancer cells (0.5µg/µl) inhibits activity of superoxid dismutase 1 (25%, p<0.01) and enzymatic activity of glutathione peroxidase (20%, p<0.01), followed by abnormal ROS accumulation (1,5-fold, p<0.05). Furthermore the specific oxidative DNA damage increased (10-fold, p<0.01) after GLC treatment, whereas the base excision DNA repair process was supressed (40%, p<0.001). Finally, above events resulted in cell cycle arrest (HCT116) or apoptosis (HCTp53-/-) and subsequent decrease of colorectal cancer cell survival (25%, p<0.05). Our results suggest that GLC extract decreases activity of the cellular antioxidant system, which leads to oxidative DNA damage and subsequently to genotoxic effects of GLC extract in colorectal cancer cell lines. These data indicate that specific oxidative DNA damage caused by natural compounds may become a potential tool for improvement of anti-cancer treatment. Acknowledgement: AMVIS LH13061 and GACR 15-14789S, AZV 15-27580A Citation Format: Alena Opattova, Andrea Cumova, Sona Vodenkova, Peter Macinga, Jozef Horak, Daniel Sliva, Pavel Vodicka. Effect of Ganoderma lucidum on DNA damage and DNA repair in colorectal cancer cell lines [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B12.