Jervine (hydriodide)

Jervine hydriodide (11-Ketocyclopamine hydriodide) is an orally active steroidal alkaloid and Hedgehog signaling pathway inhibitor. Jervine hydriodide can be isolated from Veratrum californicum. Jervine hydriodide regulates Wnt, inhibits the AKT/mTOR signaling pathway, and activates the AMPK signaling pathway. Jervine hydriodide induces DNA damage, Apoptosis, Autophagy, ROS production and Mitochondrial damage. Jervine hydriodide exhibits anti-cancer and anti-inflammatory activities. Jervine hydriodide reduces tumor growth rate and weight in xenograft models. Jervine hydriodide can be used in studies related to triple-negative breast cancer, nasopharyngeal carcinoma and non-small cell lung cancer^[1][2][3]. In Vitro:Jervine (10-40 μM; 48 h) hydriodide dose-dependently represses Hedgehog signaling in 5-8F and C666-1 NPC cells, and suppression of GLI1 is necessary for Jervine-induced autophagy, as shown by increased LC3B-II conversion and puncta formation with GLI1 knockdown^[2].
Jervine (1.25-20 μM; 1-4 days) time- and dose-dependently inhibits the proliferation of A549 and H1299 NSCLC cells, with 20 μM jervine causing the strongest reduction after 4 days of incubation^[3].
Jervine (5-10 μM; 48 h) hydriodide significantly induces apoptosis in A549 and H1299 NSCLC cells, with 10 μM causing a stronger apoptotic response^[3].
Jervine (5-10 μM; 48 h) hydriodide significantly induces apoptosis in A549 and H1299 NSCLC cells, as detected by Hoechst 33258 staining^[3].
Jervine (5-10 μM; 48 h) hydriodide dose-dependently upregulates markers of apoptosis (cleaved Caspase-3, cleaved PARP) and autophagy (LC3II) in A549 and H1299 NSCLC cells^[3].
Jervine (5-10 μM; 48 h) hydriodide dose-dependently represses AKT/mTOR signaling in A549 and H1299 NSCLC cells, as evidenced by reduced p-AKT and p-mTOR expression^[3]. In Vivo:Jervine (20 mg/kg; p.o.; daily; 24 days) hydriodide significantly suppresses nasopharyngeal carcinoma xenograft tumor growth in BALB/c nude mice by inducing apoptosis and autophagy through inhibition of Hedgehog signaling, with no detectable toxicity^[2].
Jervine (20 mg/kg; p.o.; daily; 24 days) hydriodide's suppression of nasopharyngeal carcinoma xenograft tumor growth in BALB/c nude mice is largely dependent on induction of autophagy, as co-treatment with the autophagy inhibitor 3-MA (HY-19312) abrogates its anti-tumor effects^[2].