Cucurbitacin IIa

Cucurbitacin IIa (Hemslecin A) is an orally active, blood-brain barrier-permeable EGFR inhibitor with an IC₅₀ of 1.455 nM against human EGFR. Cucurbitacin IIa induces caspase-3-dependent apoptosis, downregulates survivin expression, enhances autophagy levels, disrupts the actin cytoskeleton via actin aggregation, arrests the cell cycle at the G2/M phase, and exerts anti-inflammatory activity by inhibiting the EGFR-MAPK signaling pathway. Cucurbitacin IIa can be used in the research of inflammation-related diseases, depression, and cancers such as non-small cell lung cancer^[1][2][3][4]. In Vitro:Cucurbitacin IIa (0.1-1000 μM; 24-48 h) dose-dependently inhibits the proliferation of RAW 264.7 macrophages, with an IC₅₀ value of 122.32 μM at 24 h and 6.42 μM at 48 h^[1].
Cucurbitacin IIa (2.5-40 μM; 24 h) dose-dependently inhibits the migration of RAW 264.7 macrophages^[1].
Cucurbitacin IIa (2.5-40 μM; 5 h) does not inhibit LPS (HY-D1056)-induced TNF-α expression in RAW 264.7 macrophages^[1].
Cucurbitacin IIa (2.5-40 μM; 5 h) does not inhibit LPS-induced phosphorylation of MAPK (p38, ERK1/2, JNK) or phosphorylation of NF-κB pathway components (IκBα, p65) in RAW 264.7 macrophages^[1].
Cucurbitacin IIa (2.5-40 μM; 6-24 h) induces caspase-3-dependent apoptosis in LPS-stimulated (but not unstimulated) RAW 264.7 macrophages, which is evidenced by an increased population of cells at the sub-G0/G1 phase, elevated levels of activated caspase-3, and decreased expression of survivin^[1].
Cucurbitacin IIa (2.5-40 μM; 6-24 h) dose-dependently enhances LPS-induced autophagy in RAW 264.7 macrophages, which is evidenced by increased LC3B-II levels and enhanced LC3 puncta formation^[1].
Cucurbitacin IIa disrupts the actin cytoskeleton of RAW 264.7 macrophages by inducing actin aggregation, which is evidenced by the altered G-actin/F-actin ratio and abnormal actin distribution in treated cells^[1].
Cucurbitacin IIa (0.1-100 μg/mL; 48 h) reduces the viability and inhibits the growth of human prostate cancer cells CWR22Rv-1, PC-3 as well as human lung cancer cells NCI-H1299^[2].
Cucurbitacin IIa (10 μg/mL; 2 h) induces irreversible aggregation of filamentous actin in mouse NIH 3T3 cells transfected with EGFP-actin^[2].
Cucurbitacin IIa (50 μg/mL; 48 h) disrupts the actin cytoskeleton in human prostate cancer CWR22Rv-1 cells, but does not affect their microtubule cytoskeleton^[2].
Cucurbitacin IIa (10 μg/mL; 16 h) induces G2/M phase cell cycle arrest and increases the proportion of sub-G1 phase (apoptotic) cell population in parental human prostate cancer CWR22Rv-1 cells; however, these effects are inhibited in CWR22Rv-1 cells with δ-catenin overexpression^[2].
Cucurbitacin IIa (1-50 μg/mL; 16 h) reduces the expression levels of phosphorylated histone H3 and survivin, increases the level of cleaved PARP, and decreases the phosphorylation level of RhoA at serine 188 in human prostate cancer CWR22Rv-1 and PC-3 cells as well as human lung cancer NCI-H1299 cells, without inhibiting the phosphorylation of JAK2/STAT3^[2].
Cucurbitacin IIa (5-40 μg/mL; 72 h) induces apoptotic DNA fragmentation in human prostate cancer PC-3 and CWR22Rv-1 cells^[2].
Cucurbitacin IIa (1-50 μg/mL; 16 h) reduces the phosphorylation level of RhoA at serine 188 in human prostate cancer CWR22Rv-1 cells^[2].
Cucurbitacin IIa (50 μg/mL; 48 h) induces F-actin aggregation without altering the subcellular localization of STAT3 in human lung cancer NCI-H1299 cells^[2].
Cucurbitacin IIa (40-80 μM; 36 h) potently inhibits the proliferation of A549 cells, with an IC₅₀ of 60 μM after 36 h of treatment^[4].
Treatment of A549 cells with Cucurbitacin IIa (50-70 μM; 36 h) induces dose-dependent apoptosis in the cells^[4].
Treatment of A549 cells with Cucurbitacin IIa (50-70 μM; 36 h) induces G₂/M cell cycle arrest^[4].
Cucurbitacin IIa (60 μM; 1-5 h) alters the transcription levels of EGFR-MAPK pathway and apoptosis/cell cycle-related genes in A549 cells; significant upregulation of Raf1 and STAT3, as well as significant downregulation of MEK1 and ERK1, are observed at all time points^[4].
Cucurbitacin IIa (60 μM; 1-24 h) regulates the accumulation and phosphorylation of EGFR-MAPK pathway-related proteins, apoptosis-related proteins, and cell cycle-related proteins in A549 cells, including the continuous degradation of survivin, the continuous reduction of phosphorylated MEK1/2, and the continuous increase of phosphorylated BRAF^[4]. In Vivo:Cucurbitacin IIa (30-90 mg/kg; i.p.; daily; 10 days; 30-90 mg/kg; p.o.; daily; 10 days; 5-15 mg/kg; i.v.; daily; 10 days) dose-dependently suppresses H₂₂ hepatocellular carcinoma tumour growth in C57 mice, with the highest inhibition efficiency (57.05%) achieved at 90 mg/kg administered intraperitoneally daily for 10 days^[2].
Cucurbitacin IIa dose-dependently suppresses Lewis lung carcinoma tumour growth in C57 mice^[2].
Cucurbitacin IIa (2.5-5 mg/kg; i.p.; daily; 5 weeks) exerts dose-dependent antidepressant-like effects in CUMS-exposed mice, with the 5 mg/kg dose fully restoring behavioral, synaptic receptor expression, and CaMKII-CREB-BDNF pathway marker levels to normal, and these effects are dependent on BDNF signaling^[3].