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Isoguanosine exerts anticancer effects in Huh-7 cells by modulating ROS-dependent MAPK and AKT signaling
An-Qi Wang1, Xiao-Yu Jin2, Ying-Hua Luo3
1Department of Biochemistry and Molecular Biology, College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, China.
Isoguanosine (ISO) effectively inhibits hepatocellular carcinoma (HCC) cells by inducing apoptosis, cell cycle arrest, and reducing migration. This natural compound shows promise as an anticancer agent by targeting key signaling pathways.
Area of Science:
- Biochemistry and Molecular Biology
- Pharmacology
- Oncology
Background:
- Isoguanosine (ISO) is a naturally occurring bioactive compound with known pharmacological activities.
- Hepatocellular carcinoma (HCC) remains a significant global health challenge, necessitating novel therapeutic strategies.
- Understanding the molecular mechanisms of natural compounds like ISO is crucial for developing new anticancer agents.
Purpose of the Study:
- To investigate the inhibitory effects of Isoguanosine (ISO) on hepatocellular carcinoma (HCC) cells.
- To elucidate the underlying molecular mechanisms of ISO's action on HCC cells.
- To evaluate the potential of ISO as an anticancer therapeutic agent.
Main Methods:
- Cell viability assays (CCK-8, trypan blue, Hoechst 33342/PI staining).
- Network pharmacology and molecular docking for target prediction.
- Apoptosis assays (Annexin V-FITC/PI, flow cytometry, western blotting).
- Cell cycle analysis (Ki-67 staining, flow cytometry, western blotting).
- Cell migration assays (wound healing, Transwell, western blotting).
- Investigation of reactive oxygen species (ROS) and AKT signaling pathways.
Main Results:
- ISO demonstrated significant cytotoxic effects on HCC cell lines.
- Network pharmacology identified ROS, AKT, and MAPK pathways as key targets; molecular docking showed strong binding affinity for AKT1, CASP3, and GSK3B.
- ISO induced apoptosis via the mitochondria-dependent pathway and modulated MAPK and STAT3 signaling.
- ISO caused G2/M phase cell cycle arrest by increasing intracellular ROS levels.
- ISO inhibited cell migration by regulating the AKT signaling pathway.
- N-acetyl cysteine (NAC) pretreatment reversed ISO-induced apoptosis, cell cycle arrest, and migration inhibition.
Conclusions:
- Isoguanosine (ISO) exhibits potent anticancer properties against HCC cells by promoting apoptosis, inducing cell cycle arrest, and inhibiting migration.
- The observed effects are mediated through modulation of ROS, AKT, MAPK, and STAT3 signaling pathways.
- ISO represents a promising candidate for further pharmacological research and potential development as an anticancer agent.
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