Gundelia Tournefortii Extracts Inhibit Progressions of Hepatocellular Carcinoma in Mice Model Through Decrease in p53/Akt/PI3K Signaling Pathway

Background: Gundelia (G.) tournefortii is one of the most famous plants used in Palestine for its traditional curative and nutritive properties. We evaluated effects of Gundelia (G.) tournefortii aqueous-extract in an ex-vivo and in in-vivo animal model of hepatocellular carcinoma (HCC). Methods: : HCC cell-line (Hep3B) were injected in the back of male mice on NOD.CB17-Prkdc-scid/NCrHsD background. Tumor size, serum a-fetoprotein (αFP) and Glypican-3 (GPC3) were assessed at day 2 following HCC injections till day-12. G. tournifortii extracts were injected i.p at day 10 in HCC mice. Liver histology, hepatic-p53, p-Akt and p-PI3K expressions were evaluated. Primary-hepatocytes from HCC mice were ex-vivo treated with G. tournifortii and investigated for perturbation of the DNA cell cycle using propidium iodide (PI) staining assay, while apoptosis was estimated by staining with Annexin-V and PI by the flow cytometry. Results: : Tumor mass increase in animals with HCC and was associated with elevated aFP and GPC3 (P<0.05). Mice receiving G. tournefortii extracts s howed a significant decrease in tumor at days 12 with decreased hepatic-p53 and phosphorylated Akt/PI3K signaling pathway (p=0.001). Histology H&E staining showed remarkable reduction in inflammatory lesions in HCC livers receiving G. tournifortii extracts in line with delay in G2-M phase of HCC-primary-hepatocytes to 1.39-folds. Moreover, apoptotic activity was mostly enhanced by the 200mg/ml G. tournifortii extracts while a reduction of HCC necrosis to 2.4 fold (P<0.01). Conclusions: : Our results explored an anti-cancer, anti-proliferative and apoptotic effects of G. tournifortii in an HCC mice model and in an ex-vivo setting. G. tournifortii could be a promising future cancer remedy.