Evaluation of the Anticancer Potential of Crude, Irradiated Cerastes cerastes Snake Venom and Propolis Ethanolic Extract & Related Biological Alterations.

Mostafa I Abdelglil,Serag Eldin I Elbehairi,Mohamed A El-Desouky,Aly F Mohamed,Sanaa O Abdallah,Mohammad Y Alfaifi

doi:10.3390/molecules26227057

Mostafa I Abdelglil, Serag Eldin I Elbehairi + Show 4 more

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https://doi.org/10.3390/molecules26227057

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Abstract

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE.

Highlights

Bioactive proteins and peptides such as phospholipase A2 (PLA-2), L-aminoacid oxidase (LAAO), and disintegrin are the main constituent of snake venoms which have shown diverse biochemical activities [1]
ACTX-8-treated cells, cytochrome-C introduced into the cytoplasm, and the dispersion of mitochondrial membrane potential “MMP” were both observed, indicating that the mitochondrial pathway was implicated in ACTX-8-induced cell death and that the ratio of pro- apoptotic/anti-apoptotic Bcl-2 family member expression levels is still constant by using ACTX-8
The cytotoxic activity of Cerastes cerastes crude venom (CV), irradiated Certastes cerastes venom (IRRV), sole propolis ethanolic extract (PEE), and CV-PEE mix to A549 and PC3 cancer cells was assessed using MTT assay, which revealed that venom toxicity was concentration and cell type-dependent, as viability increased as long as concentration decreased, Figure 1a,b, and the IC50 of IRRV being significantly lower than CV and PEE, and CV-PEE mix with IC50 values in the order of 18 ± 1.26, 40 ± 3.20, 117 ± 5.85, and 119 ± 7.14 μgm/mL for PC3cell line respectively and 11 ± 0.66, 20 ± 1.80, 85 ± 5.10, and 92 ± 7.36 μgm/mL for A549 respectively

Summary

Introduction

Bioactive proteins and peptides such as phospholipase A2 (PLA-2), L-aminoacid oxidase (LAAO), and disintegrin are the main constituent of snake venoms which have shown diverse biochemical activities [1]. Cancer is related to rapid and uncontrolled cell proliferation. It has motility, invasion, angiogenesis, and metastatic features [2]. Integrins are a variety of snake venom proteins. The proteins detected in venom could contribute to the creation of novel cancer therapies [4]. ACTX-8 protein has a cytotoxic effect on a number of cancer cell types in vitro. A natural honey bee product, has been used in many studies for its antibacterial, antifungal, antiviral,hepatoprotective, and immunostimulatory activity, as it contains Flavonoids, cinnamic acid derivatives, steroids, amino acids, and vitamins such as

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