Several studies have showed that animal venoms are a source of bioactive compounds that may inhibit the growth of cancer cells, which makes them useful agents for therapeutic applications. Recently, it was established that venom toxins from scorpions induced cytotoxic, antiproliferative and apoptogenic effects on cancer cells. Therefore, the present study aims to investigate the cytotoxic activity of Androctonus australis hector (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells.
The cytotoxic and antiproliferative activities were estimated using MTT assay, lactate dehydrogenase release and clonogenic assays. Apoptosis was evaluated by Hoechst 33258 staining, DNA fragmentation assay and caspase-3 activity. Oxidative stress was analyzed by reactive oxygen species, nitric oxide, malondialdehyde and protein carbonyl levels along with assessment of antioxidant status. In addition, alteration of mitochondrial membrane potential was analyzed by JC1 fluorescent dye.
The present findings showed that F3 fraction was more cytotoxic towards NCI-H358 lung cancer cells with an IC50 of 27.05 ± 0.70 μg/mL than venom alone (396.60 ± 1.33 μg/mL) and its toxic fraction FtoxG-50 (45.86 ± 0.91 μg/mL). Nevertheless, F3 fraction was not cytotoxic at these concentrations on normal human lung fibroblast MRC-5 cells. Inhibition of NCI-H358 cell proliferation after F3 fraction exposure occurred mainly by apoptosis as evidenced by damaged nuclei, significant DNA fragmentation level and caspase-3 activation in a dose dependent manner. Moreover, F3 fraction enhanced oxidative and nitrosative stress biomarkers and dissipated mitochondrial membrane potential in lung cancer cells along with significant depletion in cellular enzymatic and non-enzymatic antioxidants. Further, the apoptosis induced by F3 fraction was markedly prevented by the antioxidant N-acetylcysteine (NAC) suggesting the potential mechanism of oxidative stress.
These findings suggest that F3 fraction could induce apoptosis in lung cancer cells through involvement of oxidative stress and mitochondrial dysfunction. Hence, these properties make F3 fraction a promising candidate for development of new anticancer agents.
Pharmacology, Toxicology and Pharmaceutical Science
4
7%
Veterinary Science and Veterinary Medicine
2
4%
Computer Science
1
2%
Other
3
6%
Unknown
23
43%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 October 2017.
All research outputs
#19,158,222
of 27,784,943 outputs
Outputs from Journal of Venomous Animals and Toxins including Tropical Diseases
#341
of 554 outputs
Outputs of similar age
#204,961
of 315,443 outputs
Outputs of similar age from Journal of Venomous Animals and Toxins including Tropical Diseases
#3
of 6 outputs
Altmetric has tracked 27,784,943 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 554 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.9. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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