Inhibitory Activity of Compounds Isolated from Ligustrum robustum (Roxb.) against HepG2 Liver Cancer Cells: Isocubein and 4‐(2‐Acetoxyethyl)phenol as Potential Candidates

Abstract Many herbal species in the genus Ligustrum have been shown to contain compounds with anti‐cancer biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum robustum (Roxb.) Blume ( L. robustum ) and evaluate their effects against liver cancer cells. As a result, seven previously reported compounds ( 1 – 7 ) were isolated, including four lignans ( 1 – 4 ) and three phenolic derivatives ( 5 – 7 ). The structures of these compounds were determined using spectroscopic methods and comparison with reported data. All isolates were assessed for their inhibitory effects on HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein ( 3 ) and 4‐(2‐acetoxyethyl)phenol ( 7 ), exhibited strong inhibitory activity against cell proliferation, with IC 50 values of 3.1±0.9 and 4.5±14 μM, respectively. Further analyses demonstrated that both compounds could suppress the formation and development of 3D tumorspheres in terms of quantity and size. Additionally, isocubein ( 3 ) and 4‐(2‐acetoxyethyl)phenol ( 7 ) exhibited the ability to inhibit the migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2 liver cancer cells of extracts and isolated compounds from L. robustum , providing valuable information for future research aiming to develop products for liver cancer treatment.