Venom of Indian monocellate cobra and Russell's viper show anticancer activity in experimental models

Debnath, Anindita; Chatterjee, Uttora; Das, Mitali; Vedasiromoni, J. R.; Gomes, Antony

doi:10.1016/j.jep.2006.12.027

Cited by 37 publications

(22 citation statements)

References 13 publications

(12 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…32,33 There are limited studies investigating the induction of apoptosis in K562 cells, after treatment with crude snake venom or purified proteins. 14,17,19,22,38,[41][42][43] Samel et al 19 investigated the effect of Sephadex G-100 chromatography fractions of M. lebetina turanica (subspecies was not mentioned in the paper but assigned according to the locality) venom and also purified HUVEC apoptosis inducing metalloproteinase (VLAIP). The first fraction reported to inhibit the viability of K562 cells about 30%.…”

Section: 3639mentioning

confidence: 99%

“…7 A considerable number of bioactive proteins have been identified from snake venoms which have potential therapeutic value against various diseases such as cancer, bacterial and fungal infections, cardiovascular disorders (e.g., acute coronary syndrome) and arthritis. 5,6,[9][10][11][12][13][14] With a special focus on anticancer activity, various snake venoms and purified proteins (e.g., metalloprotease, disintegrin, PLA 2 , LAAO, CLP) have been shown to inhibit cancer progression in vitro and/or in vivo by affecting different cellular mechanisms, including apoptosis induction.…”

Section: Introductionmentioning

confidence: 99%

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

Süzergöz¹

2016

UHOD

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In the context of searching for anticancer compounds in natural products, snake venom is one of the important sources for peptide/ protein based bioactive molecules. Proteins and peptides with anticancer activity were purified and identified from snake venoms. The aim of the present study was to determine the in vitro cytotoxicity of Macrovipera lebetina obtusa (Blunt-Nosed Viper) crude venom from southeastern Anatolia against K562 human chronic myelogenous leukemia (CML) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Adenosine tripohsphate (ATP) assays. Additionally, the apoptosis induction was assessed by morphological evaluation and immunohistochemical analysis for activated caspase-3. For histopahtological evaluation, haematoxylineosin, giemsa and papanicolau stains were used in combination. M. l. obtusa venom showed dose-dependent toxicity against K562 cells after 72 h treatment with different concentrations of crude venom. IC50 values were 0.45 and 0.37 µg/mL for MTT and ATP assays, respectively. Nuclear fragmentation and condensation, apoptotic bodies and activation of caspase-3, as an induction of apoptosis were also observed in K562 cells. Since apoptosis-inducing compounds are important for the treatment of cancer, further studies on Anatolian M. l. obtusa venom could result in the purification and identification of new proteins and peptides, which might have therapeutic value for the treatment of CML. Keywords: Anticancer, Apoptosis, Blunt-nosed viper, Macrovipera lebetina obtusa, Snake venom ÖZET Anadolu'da Yayılış Gösteren Macrovipera lebetina obtusa (Dwigubski, 1832) Zehrinin K562 İnsan Kronik Myeloid Lösemi Hücreleri Üzerinde in vitro Sitotoksik ve Apoptotik Aktiviteleri Doğal ürünlerde antikanser bileşiklerin araştırılması kapsamındaki çalışmalarda kullanılan önemli biyoaktif peptit/protein kaynaklarından biri de yılan zehridir. Yılan zehirlerinden antikanser etkili protein ve peptitler saflaştırılmış ve tanımlanmıştır. Bu çalışmanın amacı, güneydoğu Anadolu bölgesinde bulunan Macrovipera lebetina obtusa (Koca Engerek) ham zehrinin K562 insan kronik myeloid lösemi (KML) hücreleri üzerinde in vitro sitotokik etkisinin 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) ve Adenosine tripohsphate (ATP) testleri ile belirlenmesidir. Ek olarak, morfolojik değerlendirme ve aktif kaspaz-3 immünohistokimyasal analizi ile zehrin apoptotik etkisi de değerlendirilmiştir. Histopatolojik değerlendirme için hematoksilen-eozin, gimza ve papanikolau boyaları kullanılmıştır. M. l. obtusa zehrinin farklı konsantrasyonlarıyla 72 saatlik inkübasyon sonucunda K562 hücrelerine karşı doza bağlı toksisite görülmüştür. IC50 değerleri MTT ve ATP testleriyle sırasıyla 0.45 and 0.37 µg/mL olarak hesaplanmıştır. Ayrıca apoptoz uyarımının göstergeleri olarak nükleer fragmentasyon ve yoğunlaşma, apoptotik veziküller ve kaspaz-3 aktivasyonu gözlenmiştir. Apoptoza neden olan bileşiklerin kanser tedavisinde önemli bir yeri olması göz önünde bulundurulduğunda, Anadolu'da bulu...

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Section: Discussionmentioning

confidence: 99%

Section: 3639mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Süzergöz¹

2016

UHOD

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“…The biodiversity within venoms and toxins has rendered them a source of structural templates that can potentially lead to the development of novel therapeutic agents (29). Particularly, venoms of snakes, scorpions, fishes, and their corresponding active compounds such as their proteins, none protein toxins, peptides, and enzymes have shown promising anti-cancer properties (30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Persian Gulf Stonefish (Pseudosynanceia melanostigma) Venom Fractions Selectively Induce Apoptosis on Cancerous Hepatocytes from Hepatocellular Carcinoma Through ROS-Mediated Mitochondrial Pathway

et al. 2017

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Background: Globally, hepatocellular carcinoma (HCC) is the 3rd leading reason for mortality associated with cancer and the 6th most widespread malignant tumor. Objectives: This study aims to investigate selective toxicity of venom fractions of Pseudosynanceia melanostigma, commonly known as stonefish, on hepatocytes and mitochondria obtained from diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC). Methods: Different dilutions of extracted fractions from crude stonefish venom were treated on hepatocytes and mitochondria isolated from a rat model of hepatocellular carcinoma induced by diethylnitrosamine (DEN). In response to stonefish venom fractions, mitochondrial related parameters including generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, cytochrome c release, activation of caspase 3, and induction of apoptosis were investigated. Results: Our results demonstrate that for the first time, fraction 3 of Pseudosynanceia melanostigma treatment on cancerous mitochondria had a significant accumulation of reactive oxygen species (ROS). In addition, mitochondrial membrane potential (MMP) disruption, mitochondrial swelling, and cytochrome c release increased. Moreover, fraction 3 induced selective toxicity only in cancerous hepatocytes from the HCC but not those from healthy cells. Additional research also determined a significant increase in activation of caspase 3 and induction of apoptosis. Conclusions: In conclusion, this study provides evidence that fraction 3 of Pseudosynanceia melanostigma venom selectively induces apoptosis in cancerous hepatocytes from HCC through a ROS-mediated mitochondrial pathway.

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“…Under in vivo experiments, it was observed that life span of EAC (Ehrlich ascites carcinoma) mice got increased with the strengthening of impaired host anti-oxidant system. In case of in vitro study, venom showed potent cytotoxic and apoptogenic effect on human leukemic cells (U937/K562) by reducing cell proliferation rate and produced morphological alterations (Debnath et al, 2007).…”

Section: Anticancer Activity Of Snake Venommentioning

confidence: 99%

Snake Venom: A Potent Anticancer Agent

Jain

Kumar²

2012

Asian Pacific Journal of Cancer Prevention

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Since cancer is one of the leading causes of death worldwide, and there is an urgent need to find better treatment. In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. Treatment modalities comprise radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Currently, the use of chemotherapeutics remains the predominant option for clinical control. However, one of the major problems with successful cancer therapy using chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. This has led to the increased use of anticancer drugs developed from natural resources. The biodiversity of venoms and toxins makes them a unique source from which novel therapeutics may be developed. In this review, the anticancer potential of snake venom is discussed. Some of the included molecules are under clinical trial and may find application for anticancer drug development in the near future.

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Venom of Indian monocellate cobra and Russell's viper show anticancer activity in experimental models

Cited by 37 publications

References 13 publications

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

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

Persian Gulf Stonefish (Pseudosynanceia melanostigma) Venom Fractions Selectively Induce Apoptosis on Cancerous Hepatocytes from Hepatocellular Carcinoma Through ROS-Mediated Mitochondrial Pathway

Snake Venom: A Potent Anticancer Agent

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