Screening of cytotoxic and antimicrobial activity potential of AnatolianMacrovipera lebetina obtusa(Ophidia: Viperidae) crude venom

Abstract

The effects of snake venoms have been well known since ancient times. They contain a variety of biologically active proteins which have therapeutic potential. This study investigated the cytotoxic and antimicrobial activities of Anatolian Macrovipera lebetina obtusa venom against various cancer cells, Gram-negative and Gram-positive bacteria, and a fungal species. A549, HeLa, CaCo-2, U-87 MG and MCF-7 cancer cell lines and a normal cell line (Vero) were screened by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The antimicrobial activity was evaluated by determining the minimum inhibitory concentration (MIC) using the broth dilution method. The species included were Escherichia coli ATCC 25922, E. coli 0157:H7, Enterococcus faecalis, Enterococcus faecium DSM 13590, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Salmonella typhimurium CCM 5445, Proteus vulgaris ATCC 6957, Bacillus cereus ATCC 7064 and Candida albicans ATCC 10239. Half-maximal inhibitory concentration (IC 50 ) values of M. l. obtusa venom on cultured cells varied from 1.18 ± 0.11 to 12.80 ± 0.22 μg/ml, with the most potent activities against Vero, U-87 MG, MCF-7 and CaCo-2 cells. Venom showed moderate antifungal activity against C. albicans, with an MIC of 62.50 μg/ml. In short, the venom of Anatolian M. l. obtusa showed promising results as a potential source of alternative therapeutics, cytotoxic and antifungal agent prototypes.

Cytotoxic Activities of the Crude Venoms of Macrovipera lebetina lebetina from Cyprus and M. l. obtusa from Turkey (Serpentes: Viperidae) on Human Umbilical Vein Endothelial Cells

“…Crude venom of M. l. obtusa showed dose-dependent cytotoxicity against some cancer cell lines, kidney epithelial cells from African green monkey (Vero), and human embriyonic kidney 293 cells (HEK-293) in previous studies (Samel, Trummal, Siigur, & Siigur, 2012;Ozen, İğci, Yalçin, Goçmen, & Nalbantsoy, 2015;Jahromi, Mirakabadi, & Kamalzadeh, 2016;Süzergöz et al 2016;Oghalaie, Kazemi-Lomedasht, Zareinejad, & Shahbazzadeh, 2017). Moreover, dose-dependent cytotoxic activity of M. l. lebetina venom against L929 mouse fibroblast cell line was also reported previously (Nalbantsoy et al, 2012).…”

In Vitro Cytotoxic and Proapoptotic Activities of Anatolian Macrovipera Lebetina Obtusa (Dwigubski, 1832) Crude Venom on Cultured K562 Human Chronic Myelogenous Leukemia Cells.

“…Therefore, it was suggested to use different methods in combination to assess cytotoxicity. 31 Selective cytotoxic effect of Anatolian M. lebetina obtusa against various cancer cell lines (not including leukemia) has been reported previously 26 and shown to be po- 26,30 Therefore, the cytotoxic potency of the venom on various cancer cell lines should be determined by an initial screening study. It has been reported that crude venom of M. lebetina (subspecies could be assigned as M. lebetina turanica, according the origin of the samples stated in the paper) inhibited the viability of K562 cells about 10% after treating with 50 µg/mL of venom for 72 h. 19 According to our results, M. l. obtusa venom was more potent on K562 cells, compared to M. l. turanica venom.…”

“…14,20,26,30,34 These studies resulted in the description of venom proteins possessing in vitro and/or in vivo anticancer activity, including disintegrin, metalloproteinase, CLP, PLA 2 , and LAAO. Anticancer properties of snake venom proteins and their therapeutic potential have been reviewed recently by various authors.…”

“…24,25 Recently, snake venom studies aiming to make biological and proteomic characterization have been done. 8,[26][27][28][29][30] This study aimed to investigate the in vitro cytotoxicity and proapoptotic activity of crude venom extracted from Anatolian M. l. obtusa against K562 human chronic myelogenous leukemia cancer cell line.…”

Vipers of the Middle East: A Rich Source of Bioactive Molecules

“…For example, metalloproteinase from Macrovipera lebetina transmediterranea venom was identified as a myotoxin causing muscle degeneration by affecting myofiber stability and disrupting interactions of myofibers with extracellular matrix components, such as laminin and fibronectin [ 68 ]. Macrovipera lebetina venom was also described as an extraordinarily valuable source of antibacterial, antifungal, and anti-neoplastic compounds [ 69 ]. Interestingly, the venom from different Macrovipera lebetina subspecies differ in their antiproliferative and antimicrobial efficiency against different cancer cell lines or bacterial and fungal species.…”