6-Methoxydihydrosanguinarine

6-Methoxydihydrosanguinarine is an alkaloid with activity across multiple cancer cell types. 6-Methoxydihydrosanguinarine activates IRE1/JNK signaling, blocks Akt/mTOR and PI3K/AKT/mTOR pathways, reduces expression of Cdc25C, CyclinB1, Cdc2, YAP/TAZ, Survivin, GPX4, and EGFR, upregulates IRE1 and DR5, and activates JNK and caspases. 6-Methoxydihydrosanguinarine induces apoptosis, G2/M phase arrest, DNA damage, ROS generation, lipid peroxidation, ferroptosis, autophagy, and suppresses cancer cell growth. 6-Methoxydihydrosanguinarine disruptes the biofilm formation of Candida albicans (C. albicans). 6-Methoxydihydrosanguinarine can be used for the research of non-small cell lung cancer, hepatocellular carcinoma, melanoma, colon carcinoma, ovarian cancer and breast cancer^{[1][2][3][4][5][6][7]}. IC50 & Target:IC50: 0.61 μM (MCF-7 cells)
IC50: 0.54 μM (SF-268 cells)^[1] In Vitro:6-Methoxydihydrosanguinarine (0.15625-10 μM; 24 h) suppresses the viability of A549 and H1299 NSCLC cells in a dose-dependent manner, with IC₅₀ values of 2.154 μM and 2.586 μM respectively after 24 h treatment^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) induces G2/M phase arrest in A549 and H1299 NSCLC cells after 24 h treatment at 2 μM, and G1 phase arrest in H1299 cells at lower concentrations^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) downregulates cell cycle-related proteins Cdc25C, p-Cdc25C, cyclinB1, and Cdc2 in A549 and H1299 NSCLC cells after 24 h treatment^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently activates the caspase cascade and induces PARP cleavage in A549 and H1299 NSCLC cells after 24 h treatment, promoting apoptotic cell death^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently inhibits the Akt/mTOR signaling pathway in A549 and H1299 NSCLC cells after 24 h treatment by reducing Akt and p70S6K phosphorylation and total protein levels^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently blocks the YAP/TAZ oncogenic signaling axis in A549 and H1299 NSCLC cells after 24 h treatment by reducing YAP, TAZ, and survivin expression and increasing LATS1/2 phosphorylation^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently induces apoptosis in A549 and H1299 NSCLC cells after 24 h treatment^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 12 h) dose-dependently elevates intracellular ROS levels in A549 and H1299 NSCLC cells after 12 h treatment^[1].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently activates the IRE1/JNK signaling pathway in A549 and H1299 NSCLC cells after 24 h treatment^[1].
6-Methoxydihydrosanguinarine (0.125-8 μM; 24 h) dose-dependently reduces cell viability in HepG2 and Huh7 cells, with IC₅₀ values of 2.83 μM and 3.46 μM after 24 h of treatment^[2].
6-Methoxydihydrosanguinarine hydrochloride (6-MS) (1-2 μM; 12 h) dose-dependently increases intracellular ROS production in HepG2 and Huh7 cells after 12 h of treatment^[2].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently inhibits the EGFR/Akt signaling pathway, as measured by reduced EGFR expression and Akt phosphorylation, in HepG2 and Huh7 cells after 24 h of treatment^[2].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) activates the JNK and p38MAPK pathways in HepG2 and Huh7 cells after 24 h of treatment, with JNK activation being required for 6-MS-induced PARP cleavage (a marker of apoptosis)^[2].
6-Methoxydihydrosanguinarine (0.5-2 μM; 24 h) dose-dependently upregulates DR4 and DR5 expression in HepG2 and Huh7 cells after 24 h of treatment, and DR5 upregulation is required for 6-Methoxydihydrosanguinarine hydrochloride-mediated sensitization to TRAIL-induced apoptosis^[2].
6-Methoxydihydrosanguinarine (0-1.5 μM; 12 h) potently inhibits the viability of HLE and HCCLM3 hepatocellular carcinoma cells with IC₅₀ values of 1.129 μM and 1.308 μM respectively after 12 h, and is less cytotoxic to normal LX-2 hepatic stellate cells^[3].
6-Methoxydihydrosanguinarine (1 μM (HLE), 1.5 μM (HCCLM3); 12 h) induces cell death in hepatocellular carcinoma cells after 12 h of treatment, and this effect is mediated via ferroptosis, as shown by reversal with ferroptosis inhibitors^[3].
6-Methoxydihydrosanguinarine (1 μM (HLE), 1.5 μM (HCCLM3); 6 h) downregulates GPX4 expression at the transcriptional level in hepatocellular carcinoma cells after 6 h of treatment^[3].
6-Methoxydihydrosanguinarine (1-50 μM; 24 h) selectively inhibits human A375 melanoma cell viability over normal NHDF cells, with an IC₅₀ of 2.85 μM after 24 h^[4].
6-Methoxydihydrosanguinarine (0-32 μM; 24 h) potently reduces MCF-7 breast cancer cell viability in a time- and dose-dependent manner, with an IC₅₀ of 4.21 μM after 24 h^[5].
6-Methoxydihydrosanguinarine (2-4 μM; 6-24 h) induces apoptosis in MCF-7 breast cancer cells by upregulating pro-apoptotic proteins and downregulating anti-apoptotic proteins, induces autophagy by upregulating autophagy-related proteins, and inhibits the PI3K/AKT/mTOR pathway by reducing phosphorylation of key pathway proteins^[5].
6-Methoxydihydrosanguinarine downregulates the expression of EFG1, CDC35, RAS1, and TPK2, all of which are critical components of the cAMP pathway. Furthermore, 6-Methoxydihydrosanguinarine changes the membrane permeability of C. albicans and caused reactive oxygen species accumulation, leading to cell death^[6]. In Vivo:6-Methoxydihydrosanguinarine (5 mg/kg; i.p.; daily; 14 days) decreases tumor volume and weight in a Caov-3 ovarian cancer mouse xenograft model^[7].