Ganoderma lucidum and oxidative DNA damage: the role cellular antioxidant system

0475624 - ÚEM 2017 RIV HR eng C - Konferenční příspěvek (zahraniční konf.)
Opattová, Alena - Kozics, K. - Čumová, Andrea - Slíva, D. - Vodenková, S. - Vodička, Pavel
Ganoderma lucidum and oxidative DNA damage: the role cellular antioxidant system.
Cellular signalling and cancer therapy. Cavtat: EMBO Conference, 2016, s. 172-172.
[Cellular signalling and cancer therapy. Cavtat (HR), 27.05.2016-31.05.2016]
Grant CEP: GA MŠMT(CZ) LH13061; GA ČR(CZ) GA15-14789S; GA MZd(CZ) NV15-27580A
Institucionální podpora: RVO:68378041
Klíčová slova: colorectal cancer * natural compound * oxidative DNA damage * DNA repair * colorectal cell lines
Kód oboru RIV: EE - Mikrobiologie, virologie

Reactive oxygen species (ROS) are a group of highly reactive molecules tightly controlled by cellular antioxidant system. Disturbance in the prooxidation–antioxidation homeostasis can lead to ROS accumulation and consequently to DNA damage, as well as apoptosis. Many natural compounds such as Ganoderma lucidum (GLC) possess anticancer activities with the generation of ROS. Because the cancer cells are most sensitive to oxidative DNA damage as non-cancerous cells, oxidative damage is a potential target to enhance the activity of anticancer treatment by natural compounds which may lead to selective cancer cell death.
The aim of our study was to define effect of GLC extracts on cellular antioxidant system, oxidative DNA damage in colorectal cell lines (HTC116, HCT116-/-, HT29). Our results showed that 24 hrs GLC treatment (0,5mg/ml) inhibits activity of SOD1 (25%, p<0.01) in HCT116 as well as enzymatic activity of GpX (20%, p<0.01), followed by abnormal reactive oxygen species accumulation. Moreover, GLC significantly decreased a level of nuclear respiratory factor1 (NRF1), transcription factor critical for expression of antioxidant response dependent genes. The specific oxidative DNA damage increased (x%, p<0.05) after GLC treatment (0.5mg/ml, p<0.05), whereas the specific DNA repair process was inhibited. Finally, this led to decreased HCT116 survival (25%, p<0.05).
Our results clearly suggest that GLC extract strongly decrease activity of cellular antioxidant system and lead oxidative DNA damage and cell death in colorectal cancer cell lines. This indicates that natural compounds with prooxidant activity are potential target for selective improvement of anti-cancer treatment.

Trvalý link: http://hdl.handle.net/11104/0272296