Cephaeline (hydrochloride)

Cephaeline hydrochloride ((-)-Cephaeline (hydrochloride); NSC 32944 (monohydrochloride)) is a ferroptosis inducer, with broad-spectrum anticancer and antiviral activities. Cephaeline hydrochloride induces Ferroptosis by upregulating p53, inhibiting NRF2, activating ULK3, downregulating the expressions of SLC7A11 and GPX4 in a p53-dependent manner, reducing GSH and mitochondrial membrane potential, and increasing lipid peroxidation and iron accumulation. Cephaeline hydrochloride inhibits cancer cell proliferation, migration and tumor growth. Cephaeline hydrochloride inhibits Ebola virus (EBOV) VLP entry and infection, with IC₅₀ values of 3.27 μM and 22.18 μM respectively; it also inhibits Zika virus (ZIKV) NS5 RdRp activity (IC₅₀ = 976 nM), and binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp and N protein, with K_d values of 8.9 μM and 53.8 μM respectively. Cephaeline hydrochloride can be used in studies related to breast cancer, lung cancer, COVID-19, EBOV and ZIKV infections^{[1][2][3][4][5]}. In Vitro:Cephaeline hydrochloride (2.5-320 nM; 72 h) potently inhibits the proliferation of 4T1 and MDA-MB-231 breast cancer cells, with IC₅₀ values of 38.89 nM and 50.29 nM, respectively^[2].
Cephaeline hydrochloride (80 nM; 24 h) inhibits the migration of 4T1 and MDA-MB-231 breast cancer cells^[2].
Cephaeline (14 day) hydrochloride inhibits colony formation of 4T1 and MDA-MB-231 breast cancer cells, and this effect is attenuated by p53 siRNA knockdown^[2].
Cephaeline hydrochloride (5-400 nM; 24-72 h) potently inhibits the viability of H460 and A549 human lung cancer cells in a time-dependent manner, with IC₅₀ values ranging from 35 nM to 89 nM^[1].
Cephaeline hydrochloride (0.01-30 μM; 48 h) inhibits the cell viability of mucoepidermoid carcinoma cell lines UM-HMC-1, UM-HMC-2 and UM-HMC-3A, with IC₅₀ values of 0.16 μM, 2.08 μM and 0.02 μM, respectively^[4].
Cephaeline hydrochloride (at the corresponding IC₅₀ concentration; 72 h) inhibits the cell growth of UM-HMC-1 and UM-HMC-2 mucoepidermoid carcinoma cell lines, while the growth inhibitory effect on UM-HMC-3A is not statistically significant^[4].
Cephaeline hydrochloride (at respective IC₅₀ concentrations) inhibits cell migration of the mucoepidermoid carcinoma cell lines UM-HMC-1, UM-HMC-2, and UM-HMC-3A, with the onset time of inhibition varying among different cell lines^[4].
Cephaeline hydrochloride (at the corresponding IC₅₀ concentration; 24-48 h) increases the acetylation level of histone H3 lysine 9 in the mucoepidermoid carcinoma cell lines UM-HMC-1, UM-HMC-2 and UM-HMC-3A^[4].
Cephaeline hydrochloride (at the corresponding IC₅₀ concentration; 24 h) reduces the level of ALDH+ cancer stem cells in UM-HMC-2 mucoepidermoid carcinoma cells, but increases the ALDH+ level in UM-HMC-1 and UM-HMC-3A cells^[4].
Cephaeline hydrochloride (at the corresponding IC₅₀ concentration; 5 days) completely inhibits tumor sphere formation in UM-HMC-1 and UM-HMC-2 mucoepidermoid carcinoma cells, and reduces tumor sphere formation in UM-HMC-3A cells^[4].
Cephaeline hydrochloride (20-80 nM; 72 h) reduces intracellular GSH levels in a concentration-dependent manner and increases intracellular MDA levels in 4T1 and MDA-MB-231 breast cancer cells^[2].
Cephaeline hydrochloride (20-80 nM; 72 h) increases intracellular ROS levels in 4T1 and MDA-MB-231 breast cancer cells in a concentration-dependent manner^[2].
Cephaeline hydrochloride (20-80 nM; 72 h) increases the levels of total iron and Fe²⁺ in 4T1 and MDA-MB-231 breast cancer cells in a concentration-dependent manner^[2].
Cephaeline hydrochloride (20-80 nM; 72 h) downregulates the protein expression of SLC7A11 and GPX4 in a concentration-dependent manner, and upregulates the protein expression of p53 in 4T1 and MDA-MB-231 breast cancer cells^[2].
The ferroptosis and cell death induced in human lung cancer cells H460 and A549 by cephaeline hydrochloride (100 nM; 24 h) are mediated by targeting NRF2, as pretreatment with the NRF2 agonist TBHQ reverses these effects^[1].
Cephaeline hydrochloride (80 nM; 72 h) induces ferroptosis-related changes (decreased GSH levels, increased MDA and ROS levels, downregulated expression of SLC7A11 and GPX4) in 4T1 and MDA-MB-231 breast cancer cells, and these effects are blocked by p53 siRNA knockdown^[2].
Cephaeline hydrochloride (25-100 nM; 24 h) increases intracellular iron levels and reactive oxygen species levels in H460 and A549 human lung cancer cells^[1].
Cephaeline hydrochloride (25-100 nM; 24 h) regulates the expression of ferroptosis- and iron metabolism-related genes in H460 and A549 human lung cancer cells, downregulates the expression of GPX4, SLC7A11 and SLC40A1, and upregulates the expression of transferrin^[1].
Cephaeline hydrochloride (25-100 nM; 24 h) downregulates the protein levels of GPX4, SLC7A11, SLC40A1 and NRF2, while upregulates the protein expression of transferrin in human lung cancer H460 and A549 cells^[1].
Cephaeline hydrochloride (25-100 nM; 24 h) induces lipid peroxidation in human lung cancer cells H460 and A549, which can be detected by increased levels of malondialdehyde^[1].
Cephaeline hydrochloride (25-100 nM; 24 h) reduces glutathione levels in H460 and A549 human lung cancer cells, thereby impairing their antioxidant capacity^[1].
Cephaeline hydrochloride (1.950-50 μM; 90 s injection, 180 s dissociation) binds to purified SARS-CoV-2 nsp12 with a K_D value of 19.6 μM^[3].
Cephaeline hydrochloride (1.301-50 μM; 90 s injection, 180 s dissociation) binds to the SARS-CoV-2 nsp12-nsp7-nsp8-RNA complex with a K_D value of 8.94 μM^[3].
Cephaeline hydrochloride (1.301-50 μM; 90 s injection, 180 s dissociation) binds to purified SARS-CoV-2 N protein with a K_D value of 58.24 μM^[3].
Cephaeline hydrochloride (24 h) potently inhibits the replication of SARS-CoV-2 in Vero E6 cells, with an EC₅₀ of 0.0123 μM^[3].
Cephaeline (1 h) hydrochloride inhibits ZIKV NS5 RdRp polymerase activity in HEK293 cells, with an IC₅₀ value of 976 nM^[5].

Cephaeline (72 h) hydrochloride inhibits Ebola virus VLP entry into HeLa cells with an IC₅₀ value of 3.27 μM, and suppresses Ebola virus infection in Vero E6 cells with an IC₅₀ value of 22.18 nM^[5].
Cephaeline (24 h) hydrochloride exhibits cytotoxicity in Vero E6, Huh-7 and HEK293T cells, with CC₅₀ values of 49.048, 3.035 and 1.995 μM, respectively^[3]. In Vivo:hydrochloride of Cephaeline (5-10 mg/kg; i.p.; once daily) exhibits dose-dependent anti-lung cancer efficacy in BALB/c-nu mice bearing subcutaneous H460 xenografts, and induces ferroptosis-related protein changes in tumor tissues^[1].