Pentagamavunone-1 Suppresses MYCN-Positive HuH-7 Cancer Cell Growth Via Mitotic Arrest In Vitro

High expressions of MYCN is usually found in progressive liver cancer. Herein, we examined the possible effect of pentagamavunone-1 (PGV-1) on the MYCN-positive human hepatocellular carcinoma cell line in vitro based on cellular physiology and using the MYCN-positive cell line, HuH-7, as a cell model. The cytotoxic impact of PGV-1 was distinguished through the trypan blue exclusion technique. Flow cytometry was used to assess cell cycle alterations and changes in the level of intracellular reactive oxygen species (ROS). The cellular morphology of the cells was evaluated with Hoechst and X-gal staining while the level of MYCN was identified using western blotting. The results demonstrated that PGV-1 was cytotoxic to HuH-7 cells with a GI50 of 0.36 μM, which was much lower than that of sorafenib and peretinoin (GI50 of 2.07 and 45.6 μM, respectively). PGV-1–induced growth inhibition exhibited a concentration-dependent relationship, even after removal of the drug. Flow cytometry confirmed a cell cycle arrest at the G2/M phase in addition to increased intracellular ROS levels the Hoechst staining showed chromosomal condensation in the mitotic phase, particularly in prometaphase. The X-gal staining confirmed that the PGV-1–treated cells undergo senescence. While PGV-1 treatment was not proven to decrease MYCN expression in HuH-7 cells, overall, these results imply that PGV-1 is still a potential agent to inhibit MYCN-positive liver cancer cells via mitotic arrest. Copyright © 2024 by Indonesian Journal of Pharmacy (IJP).