Phytochemical Analysis and In Vivo Anticancer Effect of : Isolation and Characterization of a Promising Cytotoxic Diterpene.

is a fragrant perennial shrub of the Lamiaceae family. : The current study aimed to explore the cytotoxic potential of the -hexane fraction from aerial parts and, further, isolate its major diterpene and conduct in vitro and in vivo anticancer activities along with its molecular mechanism and synergy with doxorubicin. The hydroalcoholic extract of aerial parts was fractionated, and the -hexane fraction was analyzed via GC-MS. The major isolated diterpene, 18-epoxy-pimara-8(14),15-diene (epoxy-pimaradiene), was quantified using UPLC-PDA. Cytotoxicity assays were conducted on HCT-116, MCF-7, MDA-MB-231, and HepG2 cell lines. The synergistic effect with doxorubicin was tested on HepG2 cells. In vivo anticancer activity was evaluated using the Ehrlich ascites carcinoma model, and molecular docking analyzed Bax-Bcl2 interactions. : The -hexane fraction contained 21 compounds, mainly oxygenated diterpenes, and the major isolated compound was epoxy-pimaradiene, with a quantity of 0.3027 mg/mg. -Hexane fraction and epoxy-pimaradiene exhibited strong cytotoxicity against HepG2 cells, induced apoptosis, and G2/M arrest. The combination of epoxy-pimaradiene with doxorubicin lowered the IC of doxorubicin from 4 µM to 1.78 µM. In vivo, both reduced tumor growth and increased necrotic tumor areas. Molecular docking revealed disruption of Bax-Bcl2. The findings suggest that and its major diterpene, epoxy-pimaradiene, exhibit potent anticancer activity, particularly against liver cancer cells. Epoxy-pimaradiene enhances doxorubicin's efficacy, induces apoptosis, and inhibits tumor progression. Further studies are needed to explore their therapeutic potential.