New terpenoids from Euphorbia pekinensis with potent and selective anti-hepatocellular carcinoma activity

A new lupane- type triterpenoid and a new tirucallane- type nortriterpenoid, pekinenolone A (1) and pekinensin A (2), were isolated from the roots of Euphorbia pekinensis along with six known compounds (3-8). Their structures were established by spectroscopic analysis, NMR and ECD calculations, revealing 1 as the first new 13(18)-en-12,22-dione lupane-type triterpenoid. In anti-hepatocellular carcinoma (HCC) screenings, (3β,11β)-3,11-dihydroxylanosta-8,24-dien-7-one (8) exhibited potent cytotoxicity against Hepa1-6 cells (IC₅₀ = 4.29 ± 0.48 μM), while 1 was moderately active. Importantly, all isolates showed high selectivity, with no significant toxicity toward non-tumorigenic hepatocytes. The active compounds, 1 and 8, were found to induce apoptosis via caspase 3/7 activation. Furthermore, compound 8 inhibited cell metastasis in vitro and suppressed tumor growth in vivo, establishing it as a promising and selective lead structure for the development of new anti-HCC agents.