Exocytic fusion of lysosomes triggered by plasma membrane damage is proposed to be the major source of the membrane required for resealing. Vacuolin-1 is a potent and cell-permeable lysosomal exocytosis inhibitor which blocks the Ca2+-dependent exocytosis of lysosomes and prevents the release of lysosomal content without affecting the process of resealing[1]. Vacuolin-1 is also a potent inhibitor of the phosphatidylinositol phosphate kinase, PIKfyve with a Kd of 32 nM. In H4 cells expressing mCherry-GFP LC3, vacuolin-1 (3 μM; 24 hr) induced the accumulation of AcGFP- and mCherry-positive puncta, indicating that vacuolin-1 inhibits autophagy by inhibiting the degradation step of autophagosome. In HeLa cells, vacuolin-1 (3 μM; 24 hr) decreased mature cathepsin D levels and increased immature cathepsin D levels, suggesting that vacuolin-1 impairs the endosomal trafficking of de novo synthesized lysosomal enzymes, which in turn results in the suppression of the lysosomal degradation pathway. Moreover, vacuolin-1 treatment induced enlarged M6PR-positive vesicle formation (M6PR is a marker of transport between Golgi bodies and lysosomes) in HeLa cells, further suggesting that vacuolin-1 inhibits autophagy by inhibiting the maturation of lysosomes[2].
Vacuolin-1 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 cells
1 μM
Inhibited the colony formation ability
Oncogene. 2021 Mar;40(10):1775-1791.
Human lung cancer stem cells (LCSCs)
1 μM
Inhibited the colony formation ability
Oncogene. 2021 Mar;40(10):1775-1791.
CNE-1 cells
1 μM
Inhibited the colony formation ability
Oncogene. 2021 Mar;40(10):1775-1791.
MDA-MB-231 cells
1 μM
18 hours
Significantly inhibited the migration and invasion of cancer cells
Oncogene. 2021 Mar;40(10):1775-1791.
4T07 cells
1 μM
18 hours
Significantly inhibited the migration and invasion of cancer cells
Oncogene. 2021 Mar;40(10):1775-1791.
HeLa cells
1 μM
24 hours
Inhibited the recycling and degradation of integrins, affecting the dynamics of focal adhesions
Oncogene. 2021 Mar;40(10):1775-1791.
4T1 cells
1 μM
18 hours
Significantly inhibited the migration and invasion of cancer cells
Oncogene. 2021 Mar;40(10):1775-1791.
MA104 cells
5 μM
1 hour
To study the inhibitory effect of Vacuolin-1 on VSV-eGFP-SARS-CoV-2 infection, results showed that Vacuolin-1 effectively inhibited VSV-eGFP-SARS-CoV-2 infection
Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20803-20813.
SVG-A cells
5 μM
1 hour
To study the inhibitory effect of Vacuolin-1 on VSV-MeGFP-ZEBOV infection, results showed that Vacuolin-1 effectively inhibited VSV-MeGFP-ZEBOV infection
Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20803-20813.
HeLa cells
1 μM
6 hours
Inhibited autophagosome-lysosome fusion, leading to accumulation of autophagosomes
Autophagy. 2014;10(11):1895-905.
HeLa cells
1 μM
Inhibited the fusion of EGFR endosomes with lysosomes
To investigate the rescue effect of Vacuolin-1 on U0126-induced enucleation impairment in erythroblasts. Results showed that Vacuolin-1 partially rescued the enucleation blockage caused by U0126 and increased the number and size of vacuoles.
Blood Adv. 2021 Nov 23;5(22):4648-4661.
RAW 264.7 cells
1 μM
24 hours
To study the inhibitory effect of Vacuolin-1 on exocytosis in macrophages, results showed that Vacuolin-1 could inhibit lysosome-mediated exocytosis
Int J Nanomedicine. 2017 Aug 31;12:6383-6398.
NRK cells
5 μM
1 hour
To observe the effect of Vacuolin-1 on lysosome morphology, results showed that lysosomes were significantly enlarged after Vacuolin-1 treatment
EMBO Rep. 2005 Sep;6(9):843-7.
HeLa cells
1 μM
1 hour
To observe the effect of Vacuolin-1 on lysosome morphology, results showed that lysosomes were significantly enlarged after Vacuolin-1 treatment
EMBO Rep. 2005 Sep;6(9):843-7.
NB4 cells
0.25 µM
72 hours
Vacuolin-1 enhanced RA-induced CD11b expression in NB4 cells.
Cell Biosci. 2022 Nov 3;12(1):179.
HL-60 cells
0.25 µM
5 hours, 24 hours, 48 hours, 72 hours
Vacuolin-1 enhanced RA-induced differentiation of HL-60 cells, as evidenced by increased CD11b expression, ROS production, and G1/0 cell cycle arrest.
Cell Biosci. 2022 Nov 3;12(1):179.
HeLa cells
5 μM or 10 μM
2 hours
Inhibits ionomycin-induced release of lysosomal β-hexosaminidase.
EMBO Rep. 2004 Sep;5(9):883-8.
BSC-1 cells
1 μM
1 hour
Induces vacuole formation in endosomal and lysosomal compartments without affecting markers for Golgi apparatus, ER, and enlargeosomes.
EMBO Rep. 2004 Sep;5(9):883-8.
Vacuolin-1 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
MMTV-PyMT transgenic mice
Mammary adenocarcinoma model
Oral
15 mg/kg or 30 mg/kg daily
Once daily for 2 months
Significantly inhibited tumor growth and metastasis of mammary adenocarcinomas
搜索
