Garcinone E

Garcinone E is a xanthone natural product that exerts antioxidant, anti-inflammatory, antitumor, and immunomodulatory activities by inhibiting JNK, TNF-α, NF-κB, and FAS, and enhancing Nrf2 signaling pathways. Garcinone E can be used in research on autoimmune hepatitis, obesity, and various cancers (including breast cancer, colorectal cancer, cervical cancer, liver cancer, lung cancer, and gastric cancer)^{[1][2][3][4][5][6]}. In Vitro:Garcinone E (16-128 μM; 24-72 h) selectively decreases the proliferation of human HeLa cervical cancer cells in a concentration- and time-dependent manner, restricting cell viability to approximately 5% after treatment with 128 μM for 72 h^[2].
Garcinone E (16-128 μM; 48 h) significantly inhibits the clonogenic ability of human HeLa cervical cancer cells, reducing colony formation from 450 to nearly 50 at 128 μM^[2].
Garcinone E (16-128 μM; 12 h) reduces the migration and invasion abilities of human HeLa cervical cancer cells in a dose-dependent manner^[2].
Garcinone E (GE) exhibits cytotoxic activity against MDA-MB-231, MCF-7, and 4T1 breast cancer cells, with IC₅₀ values of 0.68, 2.27, and 1.21 μM, respectively^[4].
Garcinone E (25-100 nM) dose-dependently inhibits M2 macrophage-induced proliferation of MCF-7, MDA-MB-231, 4T1, and HUVEC cells, as evidenced by reduced BrdU incorporation^[4].
Garcinone E (GAR E) (0.5-2 μM; 24 h) inhibits colony formation and migration in HT-29 and Caco-2 human colorectal cancer cells in a concentration-dependent manner^[5].
Garcinone E (0.5-2 μM; 24 h) reduces the cell viability of HT-29 and Caco-2 human colorectal cancer cells in a dose-dependent manner, an effect that is partially reversed by Acetylcysteine (NAC) (HY-B0215) and attenuated by the JNK inhibitor SP600125 (HY-12041)^[5].

Garcinone E (1-2 μM; 2 h) induces the production of intracellular reactive oxygen species in HT-29 and Caco-2 human colorectal cancer cells^[5].
Garcinone E (2 μM; 24 h) induces loss of mitochondrial membrane potential in HT-29 and Caco-2 human colorectal cancer cells, an effect that is reversed by the antioxidant NAC and attenuated by the JNK inhibitor SP600125^[5].
Garcinone E (2 μM; 24 h) induces apoptosis in HT-29 and Caco-2 human colorectal cancer cells, an effect that is abolished by the antioxidant Acetylcysteine or attenuated by the JNK inhibitor SP600125^[5].
Garcinone E (1 μM; 48 h) induces cell cycle arrest at the Sub G1 phase in HT-29 and Caco-2 human colorectal cancer cells, an effect that is abolished by N-acetylcysteine pretreatment and attenuated by the JNK inhibitor SP600125^[5].
Garcinone E (2 μM; 24 h) activates the JNK signaling pathway in HT-29 human colorectal cancer cells and induces the expression of apoptosis-related proteins, an effect that is abolished by the antioxidant NAC^[5].
Garcinone E (2 μM; 24 h) activates the JNK signaling pathway and induces the expression of apoptosis-related proteins in Caco-2 human colorectal cancer cells, an effect that is abolished by the antioxidant NAC^[5].
Garcinone E (2 μM; 24 h) activates the JNK signaling pathway and induces the expression of apoptosis-related proteins in HT-29 and Caco-2 human colorectal cancer cells, and this effect is abolished by the JNK inhibitor SP600125^[5].
Garcinone E (16-128 μM) induces apoptotic cell death in human HeLa cervical cancer cells in a dose-dependent manner^[2].
Garcinone E (16-128 μM; 24 h) induces caspase-dependent apoptotic cell death in human HeLa cervical cancer cells, manifested by upregulation of Bax and caspases and downregulation of Bcl-2^[2].
Garcinone E (16-128 μM; 24 h) induces G2/M phase cell cycle arrest in human HeLa cervical cancer cells^[2].
Garcinone E acts as a potent, rapidly binding inhibitor of the overall FAS reaction, with an IC₅₀ of 3.3 μM^[3].
Garcinone E inhibits the KR domain activity of FAS with an IC₅₀ of 14.6 μM, which is weaker than its effect on the overall reaction^[3].
Garcinone E (20.0 μM) acts as a slow-binding irreversible inhibitor of the overall FAS reaction (k_obs = 0.009 min^-1 at 20 μM), but exhibits only weak irreversible inhibition of the KR domain (k_obs = 0.0004 min^-1)^[3].
Garcinone E (50 and 100 nM) significantly downregulates the mRNA expression of M2-specific markers (CD206, Arg-1, Fizz-1, Ym1) in IL-4 + IL-13-treated RAW 264.7 macrophages^[4].
Garcinone E (25-100 nM) inhibits IL-4/IL-13-induced STAT6 phosphorylation, Arg-1 expression, and nuclear translocation in RAW 264.7 macrophages^[4].
Garcinone E (25-100 nM) inhibits M2 macrophage-induced angiogenesis in HUVECs^[4].
Garcinone E (50 and 100 nM) reduces the secretion of pro-angiogenic and pro-metastatic factors, including VEGF, MMP9, MMP2, and TGF-β, from M2-polarized RAW 264.7 macrophages^[4].
Garcinone E (2.5-20 μmol/L; 24-72 h) significantly inhibits the viability of HK1, HONE1, and S18 cells, with 72 h IC₅₀ values of 7.64, 8.83, and 4.65 μmol/L, respectively^[6].
Garcinone E (1.25-5 μmol/L; 9-12 days) reduces the colony-forming ability of HK1, HONE1, and S18 cells and statistically confirms the decrease in relative colony area of HK1 and HONE1 cells^[6].
Garcinone E (7.5-12.5 μmol/L; 24 h) induces cell cycle arrest at the G0/G1 and S phases in HK1 and HONE1 cells^[6].
Garcinone E (5-10 μmol/L; 48 h) increases the number of autophagosomes in HK1 and HONE1 cells^[6].
Garcinone E (5-10 μmol/L; 48 h) blocks autophagic flux in HK1, HONE1, and S18 cells, manifested as accumulation of yellow puncta^[6].
Garcinone E (5-10 μmol/L; 48 h) induces lysosomal damage and blocks autophagosome-lysosome fusion in HK1 and S18 cells^[6].
Garcinone E (5-10 μmol/L; 48 h) blocks autophagic flux in HK1 and HONE1 cells by inhibiting autophagosome-lysosome fusion^[6].
Garcinone E (5-10 μmol/L; 24 h) enhances the expression of cell cycle-related proteins, autophagy-related proteins, and signaling pathway proteins in HK1 and HONE1 cells^[6].
Treatment with Garcinone E (5-10 μmol/L; 24 h) significantly alters the mRNA expression profiles in HK1 and HONE1 cells and enriches autophagy-related pathways^[6].
Garcinone E (5-10 μmol/L; 24 h) upregulates BECN1, SQSTM1, and MAP1LC3B mRNA and downregulates AKT1 mRNA in HK1 and HONE1 cells^[6]. In Vivo:Garcinone E (25-50 mg/kg; once daily; for 5 consecutive days) exhibits dose-dependent hepatoprotective efficacy against Con-A-induced autoimmune hepatitis, primarily through modulation of the Nrf2/HO-1, NF-κB, and TNF-α/JNK axes^[1].
Garcinone E (2 mg/kg; i.p.; once every other day) effectively inhibits tumor growth and lung metastasis in the 4T1 mouse breast cancer model, with a 52% reduction in tumor volume and a 50% reduction in lung metastatic nodules^[4].
Garcinone E (2 mg/kg; i.p.; every other day) effectively inhibits breast cancer lung metastasis in a tail vein injection model, significantly reducing the number of metastatic nodules at 20 days (105 vs. 47)^[4].
Garcinone E (35 mg/kg; i.p.; once every three days; for 18 days) inhibits the growth of S18 nasopharyngeal carcinoma xenografts in nude mice without severe side effects^[6].
Garcinone E (2.5-5 mg/kg; i.p.; 2 days) significantly inhibits tumor growth in the HT-29 xenograft mouse model, reducing tumor volume to as low as 129 mm³ at a dose of 5 mg/kg^[5].