Actinonin, a peptidomimetic antibiotic that inhibits HsPDF(human peptide deformylase), also inhibits the proliferation of 16 human cancer cell lines. Actinonin inhibits cell growth in various human tumor cell lines. The IC50 of 4, 6.9, 12.8, 16.6, 27.4, 15.7 and 49.3 μM for Raji cells, MDA-MB-468 cells,PC3 cells, SK-LC-19 cells, Hela cells, HT-1080 cells and AL67 cells, respectively.. In animal models, oral or parenteral actinonin was well tolerated and inhibited human prostate cancer and lung cancer growth. Actinonin has been safely administered to mice as an antibiotic at doses up to 400 mg/kg. Actinonin does not appear to have significant toxicity to normal tissues, despite its antitumor activity in vitro. Remarkably, Actinonin exhibits significant antitumor activity when given i.p. or orally in a CWR22 human prostate tumor xenograft model in nude mice. During treatment, the animals show no signs of toxicity[2]. Actinonin which has been found to be an inhibitor of aminopeptidase M (EC 3.4.11.2) also inhibited enkephalinase A (EC 3.4.24.11) and enkephalin aminopeptidase which were partially purified from the corpus striatum membrane of guinea-pig brain. The IC50 values were 5.6 microM for enkephalinase A and 0.39 microM for enkephalin aminopeptidase. The analgesic effect of [Met5]enkephalin injected intracisternally (i.cist., 50 micrograms) was potentiated by an intraperitoneal (i.p., 100 and 300 mg/kg) as well as an i.cist. (25 micrograms) injection of actinonin. Actinonin was found to inhibit all three enzymes of enkephalin metabolism and, when given peripherally, to potentiate enkephalin analgesia[3]. Anti-VaPDF (V. anguillarum PDF) and anti-V. anguillarum activities of actinonin were dose-dependent, and the IC50 values were 6.94 and 2.85 μM, respectively[4].
Actinonin 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HT22 cells
2μM
24 h
To evaluate the protective effects of Actinonin against mutant Tau-induced mitochondrial and synaptic toxicities. Results showed that Actinonin treatment increased the expression of mitochondrial fusion genes, decreased the expression of mitochondrial fission genes, and improved mitochondrial respiration and cell survival.
Pharmacol Res. 2021 Dec;174:105973
P493 cells
26 μM
Actinonin selectively kills c-Myc-overexpressing P493 cells regardless of proliferation status
Cell Death Dis. 2014 Mar 27;5(3):e1152
HeLa cells
150 μM
6 h
Actinonin treatment led to YFP-Parkin accumulation on mitochondria, but Parkin recruitment was not observed in PINK1 KO cells.
J Cell Biol. 2017 Oct 2;216(10):3231-3247
HeLa cells
150 μM
4 h
Actinonin treatment caused YFP-Parkin to accumulate in focal spots on polarized mitochondrial subdomains.
J Cell Biol. 2017 Oct 2;216(10):3231-3247
NCI-A549 cells
250 μM
48 h
To study the uptake of Actinonin nanoformulation in NCI-A549 cells, results showed apoptotic features such as cellular blebbing, loss of mitochondrial integrity, numerous vacuoles and shrunken nucleus.
Drug Deliv. 2022 Dec;29(1):2403-2413
SH-SY5Y cells
5, 10, 20, 30, 50, 100 µg/ml
3 h
To evaluate the potency of HIF PHD inhibitors and compare the IC50 values of different inhibitors. Results showed that oxyquinoline-type inhibitors were more effective than roxadustat and vadadustat in the HIF ODD-luc reporter assay.
J Clin Invest. 2004 Oct;114(8):1107-16
Arabidopsis thaliana cells
100 μM
Study the effect of actinonin on chloroplast development, showing induction of an albino phenotype.
EMBO J. 2003 Jan 2;22(1):13-23
K562 cells
26 μM
5 days
Investigate the inhibitory effect of Actinonin on K562 cell proliferation, results showed Actinonin inhibits cell proliferation through intracellular interactions
Cancer Lett. 2002 Aug 28;182(2):113-9.
U937 cells
13 μM
5 days
Investigate the inhibitory effect of Actinonin on U937 cell proliferation, results showed Actinonin inhibits cell proliferation through intracellular interactions
Cancer Lett. 2002 Aug 28;182(2):113-9.
RBL-2H3 mast cells
100 µM
1 h
Inhibition of Mep1A activity, significantly reducing TNF-α mRNA and protein levels in IgE-treated mast cells
Br J Pharmacol. 2020 Jun;177(12):2872-2885
Actinonin 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
CLP model
Intraperitoneal injection
400 μg
0 and 6 hours post-surgery
Actinonin reduced renal injury in the CLP mouse model
Kidney Int. 2006 Aug;70(3):496-506
BALB/c mice
Lung adenocarcinoma model
Intraperitoneal injection
150 mg/kg
Free Actinonin five times per week, nanoformulation two times per week, for one week
To evaluate the therapeutic efficacy of free and nanoformulated Actinonin in lung adenocarcinoma model, results showed comparable efficacy of nanoformulation to free drug in terms of reduced tumor burden, 100% survival and downregulation of EGFR, FOLR1 and PDF expression.
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