Medicinal value of animal venom for treatment of Cancer in Humans - A Review
Languages of publication
Since cancer is one of the leading causes 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. Anticancer drug developments from natural resources are ventured throughout the world. Venoms of several animal species including snake, scorpion, frog, spider etc. and their active components in the form of peptides, enzymes etc. have shown promising therapeutic potential against cancer. In the present review, the anticancer potential of venoms as well as their biochemical derivatives from some vertebrates like snake or frog or some venomous arthropods like scorpion, honey bee, wasps, beetles, caterpillars, ants, centipedes and spiders has been discussed. Some of these molecules are in the clinical trials and may find their way towards anticancer drug development in the near future. The recognition that cancer is fundamentally a genetic disease has opened enormous opportunities for preventing and treating the disease and most of the molecular biological based treatment are cost effective. The search for alternative economical and natural sources for cancer medicines is of utmost need for the future in combating this dreadful disease that is spreading at fast rate in the present era.
- Department of Zoology, Scottish Church College, 1 & 3 Urquhart Square, Kolkata - 700006, India
- Department of Biological, Sciences Presidency University 86/1, College Street, Kolkata – 700073, India
- Department of Zoology, Scottish Church College, Kolkata, India
- Department of Zoology, Vivekananda College, Thakurpukur, Kolkata - 700063, India
-  AAl-Sadoon MK, Abdel-Maksoud MA, Rabah DM, Badr G (2012). Induction of apoptosis and growth arrest in human breast carcinoma cells by a snake (walterinnesia aegyptia) venom combined with silica nanoparticles: crosstalk between Bcl2 and Caspase 3. Cell Physiol Biochem, 30: 653-65.
-  Bai X, Cerimele F, Ushio-Fukai M, Waqas M, Campbell P M, Govindarajan B, Der C J, Battle T, Frank DA, Ye K, Murad E, Dubiel W, Soff G, Arbise J L (2003). Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem, 278: 35501-35507.
-  Barnett GC, West CM, Dunning AM, et al., (2009). Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype, Nature Rev Cancer, 9: 134-142.
-  Baskar R, Lee KA, Yeo R, Yeoh KW (2012). Cancer and radiation therapy: current advances and future directions, Int J Med Sci, 9: 193-199.
-  Bradbury MW, Deane R (1993). Permeability of the blood-brain barrier to lead, Neurotoxicology, 14: 131-136.
-  Braganca BM and Khandeparker VG (1966). Phospholipase C activity of cobra venom and lysis of Yoshida sarcoma cells, Life Sci, 5: 1911.
-  Bernheimer AW, Linder R, Weinstein SA, Kim KS (1987). Isolation and characterization of phospholipase B from venom of Collett’s snake Pseudechis colletti, Toxicon, 25: 547.
-  Calmette A, Saenz A, Costil L (1993). Effects of du venimde cobra sur les greffes cancereuses et sur le cancer spontanea (adeno carcinoma) de la souris, C R Acad Sci, 197: 205.
-  Chen HM, Wang W, Smith D, Chan SC (1997). Effects of antibacterial peptide cecropin B and its analogues, cecropin B-1 and cecropin B-2,on liposome,bacteria and cancer cells, Biochim Biophys Acta 1336:171-179.
-  Chen Y, Xiang J, Gu W and Xu M (1998). Chemical constituents of Bufo siccus, Zhongguo Zhong Yao Za Zhi, 23: 620
-  Chen YJ, Shieh CJ, Tsai THE, et al., (2005) Inhibitory effect of norcantharidin, a derivative compound from blister beetles on tumor invasion and metastasis CT26 colorectal adenocarcinoma cells, Anticancer Drugs 16: 293-299.
-  Csoka AB, Frost GI , Stern R (2001). The six hyaluronidase like genes in the mouse and human genomes, Matrix Biol, 20: 499-508
-  Cura JE, Blanzaco DP, Brisson C, et al., (2002). Phase I and pharmacokinetics study of crotoxin (Cytotoxic PLA2, NSC624244) in Patients with advanced cancer, Clin Cancer Res, 8: 1033-41.
-  Da Silva RJ, Fecchio D, Barraviera B (1996). Antitumor effect of snake venom, J Venom Anim Toxins, 2.
-  Dang YJ, Zhu CY (2013). Oral bioavailability of cantharidin-loaded solid lipid nanoparticles, BMC Chinese Medicine, 8(1).
-  Daniele JJ, Bianco ID, Delgado C, Briones CD, Fidelio GD (1997). A new PLA2 isoform isolated from Bothrops newweidii (Yiaraca chica) venom with novel kinetic and chromatographic properties, Toxicon, 35: 1205.
-  Das M, Dasgupta SC & Gomes A (1998). Immunomodulatory and antineoplastic activity of common Indian toad (Bufo melanostictus Schneider) skin extract, Indian J Pharmacol, 30: 311.
-  Debnath A, Chatterjee U, Das M, Vedasiromoni JR, Gomes A (2007). Venom of Indian monocellate cobra and Russell’s viper show anticancer activity in experimental models, J Ethnopharmacol, 111: 681.
-  Deshane J, Garner CC, Sontheimer H (2003). Chlorotoxin inhibits glioma cells invasion via matrix metalloproteinase-2, J. Biol. Chem., 278: 4135-4144
-  Dorn DC, Kou CA, Png KJ, Moore MA (2009). The effect of cantharidins on leukemic stem cells, Int J Cancer, 124: 2186-2199
-  Efferth T, Rauh R, Kahl S, et al., (2005). Molecular modes of action of cantharidines in tumor cells, Biochem Pharmacol, 69: 811-818.
-  Escoubas P (2006). Mass spectrometry in toxicology: a 21st century technology for the study of biopolymers from venoms, Toxicon, 47: 609-613.
-  Fan YZ, Fu JY, Zhao ZM, Chen CQ (2004). Influence of norcantharidin on proliferation, proliferation-related gene proteins proliferating cell nuclear antigen and Ki-67 of human gallbladder carcinoma GBC-SD cells. Hepatobiliary Pancreat Dis Int 3:603-607.
-  Fan YZ, Fu JY, Zhao ZM, Chen CQ (2007). Inhibitory effects of norcantharidin on the growth of human gallbladder carcinoma GBC-SD cells in vitro, Hepatobiliary Pancreat Dis Int, 6:72-80.
-  Faure G, Harvey AL, Thomson E, et al., (1993). Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action, Eur J Biochem, 214: 491-6.
-  Favreau P, Menin L, Michalet S, Perret F, Cheneval O, Stocklin M, Bulet P, Stocklin R (2006). Mass spectrometry strategies for venom mapping and peptide sequencing from crude venoms: case application with single arthropod specimen, Toxicon, 47: 676-687.
-  Feng L, Gao R, Gopalakrishnakone P,(2008). Isolation and characterization of a hyaluronidase from the venom of Chinese red scorpion (Buthus martensi), Comp Biohem Physiol C Toxicol Pharmacol, 148: 250.
-  Ferrer (2001). Snake venom: The pain and potential of the venom, The cold blooded news, 28.
-  G Davies, L A Martin, N Sacks, M Dowsett (2002). Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX 2 inhibitor in breast cancer chemoprevention, Ann Oncol, 13: 669-678.
-  Galvis CEP, Mendez LYV, Kouznetsov VV (2013). Cantharidin-based small molecules as potential therapeutic agents, Chemical Biology and Drug Design, 82: 477–499.
-  Gao R, Zhang Y,Gopalakrishnakone P, (2008). Purification and N-terminal sequence of a serine proteinase like protein (BMK-CBP) from the venom of Chinese scorpion (Buthus martensii Karsch), Toxicon, 52: 348
-  Geissler M, Weth R (2002). Immunotherapy: new insights, Praxis, 91: 2236-46.
-  Ghavami S, Asoodeh A, Kloinisch T, Halayko A J, Kadkhod K, Kroczak T J, Gibson S B, Booy E P, Naderi-Manesh H and Los M (2008). Brevinin 2R(1) semi-selctively kills cancer cells by adistinc mechanism which involves the lysosomal mitochondrial death pathway, J Cell Mol Med, 12:1005.
-  Giri B and Gomes A (2004). Antineoplastic activity of Indian toad (Bufo melanostictus Schneider) skin extract on EAC cells and human leukemic (U937 and HL60) cell line, Indian J Pharmacol, 36: S83.
-  Girisk K S and Kemparaju K (2007). The magic glue hyaluronan and its eraser hyaluronidases : a biologically overview, Life Sci, 80: 921-943.
-  Gomes A, Choudhury SR, Saha A, et al., (2007). A heat stable protein toxin (drCT-I) from the Indian Viper (Daboia russelli russelli) venom having antiproliferative, cytotoxic and apoptotic activities, Toxicon: Official J Int Society on Toxinology, 49: 46-56.
-  Gomes A, Bhattacharjee P, Mishra R, et al., (2010). Anticancer potential of animal venoms and toxins, Indian J Exp Biol, 48: 93-103.
-  Goudet C, Chi, CW, Tytgat, J (2002). An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch, Toxicon, 40: 403-410.
-  Gupta SD, Gomes A, Debnath A, Saha A and Gomes A (2008). Apoptosis induction in human leukemic cells by a novel protein Bengalin, isolated from Indian Black scorpion venom: through mitochondrial pathway and inhibition of Heat Shock Proteins, Chem Biol Interact, doi:10.1016/j.cbi.
-  Gwee MCE, Nirthanan S, Khoo HE, Gopalakrihnakone P, Kini RM, Cheah LS (2002). Autonomic effects of some scorpion venoms and toxins, Clin Exp Pharm Physiol, 29: 795-801.
-  Hashimoto S, Jing Y, Kawazoe N, Masuda Y, Nakajo S, Yoshida Nakaya K (1997). Bufalin reduces the level of topoisomerase II in human lekumia cells and affects the cytoxicity of anticancer drugs, Leuk Res, 21: 875.
-  Hill TA, Stewart SG, Ackland SP, et al., (2007). Norcantharimides, synthesis and anti-cancer activity: synthesis of new norcantharidin analogues and their anticancer evaluation, Bio org Med Chem, 15: 6126-6134.
-  Hill TA, Stewart SG, Sauer B, et al., (2007) Heterocyclic substituted cantharidin and norcantharidin analogues-synthesis, protein phosphatase (1 and 2A) inhibition, and anti-cancer activity, Bio org Med Chem Lett, 17: 3392-3397.
-  Huang WW, Ko SW, Tsai HY, et al., (2011). Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo205cells through inhibition of CDK1 activity and caspase-dependent signalling pathways, International Journal of Oncology, 38(4): 1067–1073.
-  Huang YP, Ni CH, Lu CC, et al., (2013). Suppressions of migration and invasion by cantharidin in TSGH-8301 human bladder carcinoma cells through the inhibitions of matrix metalloproteinase-2/-9 signalling, Evidence-Based Complementary and Alternative Medicine, Article ID 190281.
-  Kang IC, Lee YD, Kim DS (1999). A novel disintegrin salmosin inhibits tumor angiogenesis, Cancer Res, 59: 3754-60.
-  Ko WS, Park TY, Park C, Kim YH, Yoon HJ, Lee SY, Hong SH, Choi BT, Lee YT, Choi YH (2005). Induction of apoptosis by Chan Su, a traditional Chinese medicine, in human bladder carcinoma T24 cell, Oncol Rep, 14: 475.
-  Kok SH, Cheng SJ, Hong CY, et al.(2005) Norcantharidin –induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio. Cancer Lett 217:43-52.
-  Kruger C, Greten TF, Korangy F (2007). Immune based therapies in cancer, Histology Histopathology, 22: 687-96.
-  Lai D, Visser-Grieve S, Yang X (2012). Tumour suppressor genes in chemotherapeutic drug response, Biosci Reports, 32: 361-74.
-  Liu D and Chen Z (2009).The effects of cantharidin and cantharidin derivatives on tumor cells, Anticancer Agents Med Chem, 9: 392-396.
-  Liu S, Yu M, He Y, Xiao L, Wang F, Song C, Sun S, Ling C, Xu Z (2008). Melittin prevents liver cancer cells metastasis through inhibition of the Rac-1-dependent pathway, Hepatology, 47(6):1964-1973.
-  Liu Z, Zhao Y, Li J, Xu S, Liu C, Zhu Y, Liang S (2012). The venom of the spider Macrothele raveni induces apoptosis in the myelogenous leukemia K562 cell line, Leuk Res, 36(8): 1063-1066.
-  Markland FS, Shieh K, Zhou Q, et al., (2001). A novel snake venom disintegrin that inhibits human ovarian cancer dissemination and angiogenesis in an orthotopic nude mouse model, Haemostasis, 31: 183-191.
-  Matsushita O, Okabi A (2001). Clostridial hydrolytic enzymes degrading extracellular components, Toxicon, 39: 1769-1780.
-  Mc Ferrin MB, Sontheimer H (2006). A role for ion channels in glioma cell invasion, Neuron Glia Biol, 2: 39-49.
-  Menez A, Stocklin R, Mebs D (2006). “Venomics” or: the Venomous systems genome project, Toxicon, 47: 255-259.
-  Moon DO, Park SY, Heo MS, Kim KC, Park C, Ko WS (2006). Key regulators in bee venom induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through down regulation of ERK and Akt, International Immunopharmacology, 6(12): 1796-1807.
-  Moore AJ, Devine DA, Bibby MC (1994). Preliminary experimental anticancer activity of cecropins, Pept Res, 7: 265-269.
-  Moreno M, Zurita E, Giralt E (2014). Delivering wasp venom for cancer therapy, Journal of controlled release, 182:13DOI:10.1016/j.jconrel
-  Muller GJ (1993). Scorpionism in South Africa- a report of 42 serious scorpion envenomations, South Afr Med J, 83: 405-411.
-  Nam KW, Je KH, Lee JH, Han HJ, Lee HJ, Kang SK, Mar W (2003). Inhibition of COX-2 activity and proinflammatory cytokines (TNF-α and IL-1β) production by water soluble sub-fractionated parts from bee (Apis mellifera) venom, Arch Pharm Res, 26(5): 383-388.
-  Orentas RJ, Lee DW, Mackall C (2012). Immunotherapy targets in pediatric cancer, Frontiers in Oncol, 2: 3.
-  Ouadid-Ahidouch H, Roudbaraki M, Ahidouch A, Delcourt P, Prevarskaya N (2004). Cell cycle dependent expression of the large Ca++ activated K+ channels in breast cancer cells, Biochem Biophys Res Commun, 316: 244.
-  Pawelek PD, Cheah J, Coulombe R, et al., (2000). The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site, The EMBO J, 19: 4204-4215.
-  Peng F, Wei YQ, Tian L, et al., (2002). Induction of apoptosis by norcanthardin in human colorectal carcinoma cell lines: involvement of the CD-95 receptor/ligand, J Cancer Res Clin Oncol, 128: 223-230.
-  Possani, LD, Merino E, Corona M, Bolivar F, Becerril B (2000). Peptides and genes coding for scorpion toxins that affect ion-channels, Bio-chimie, 82: 861-868.
-  Qiao L, Huang YF, Cao JQ, Zhou YZ, Qi XL, Pei YH (2008). One new bufadienolide from Chinese drug ‘Chan Su’, J Asian Nat Prod Res, 10: 233
-  Rauh R, Kahl S, Boechzelt H et al., (2007). Molecular biology of Cantharidin in cancer cells, Chin Med, 2: 8.
-  Rudd CJ, Viskatis LJ, Vidal JC, Etcheverry MA (1994). In vitro comparison of cytotoxic effects of crotoxin against three human tumors and a normal human epidermal keratinocyte cell line, Invest New Drugs, 12: 183-4.
-  Sagawa M, Nakazato T, Uchida et al., (2008). Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathway, Cancer Sci, 99:1820-1826.
-  Shou LM, Zhang QY, Li W et al., (2013). Cantharidin and norcantharidin inhibit the ability of MCF-7cells to adhere to platelets via protein kinase C pathway-dependent downregulation of 𝛼2 integrin, Oncology Reports, 30: 1059-1066.
-  Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012.,CA: A Cancer J for Clin, 62:10-29.
-  Song JK, Jo MR, Park MH, et al., (2012). Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor kappaB and signal transducer and activator of transcription 3, Archives of Pharmacal Res, 35: 867-76.
-  Sonoda Y, Hada N, Kaneda T, Suzuki T, Ohshio T, Takeda T, Kasahara T (2008). A synthetic glycosphingolipid –induced antiproliferative effect in melanoma cells is associated with suppression of FAK,Akt and Erk activation, Biol Pharm Bull, 31: 1279-1283.
-  Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H (1998). Use of chlorotoxin for targeting of primary brain tumors, Cancer Res, 58: 4871-4879.
-  Soroceanu L, Manning Jr, TJ, Sontheimer H (1999). Modulation of glioma cell migration and invasion using Cl- and K+ ion channels blockers, J Neurosci, 19: 5942-5954.
-  Suttmann H, Retz M, Paulsen F, Harder J, Zwergel U, Kamradt J, Wullich B, Unteregger G, Stockle M, Lehmann J (2008). Antimicrobial peptides of cecropin family Show potent antitumor activity against bladder cancer cells, BMC Urol, 3:8.
-  Veiseh M, Gabikian P, Bahrami SB, Veiseh O, Zhang M, Hackman RC, Ravanpay AC, Stroud MR, Kusuma Y, Hansen SJ, Kwok D, Munoz NM, Sze RW, Grady WM, Greenberg NM, Ellenbogen RG, Olson JM (2007). Tumor paint: a chlorotoxin: Cy5.5 bioconjugate for intraoperative visualization of cancer foci, Cancer Res, 67: 6882-6888.
-  W Li, L Xie, Z Chen, et al., (2010). Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell cycle arrest and apoptosis, Cancer Science, 101(5): 1226-1233.
-  Wang CC, Wu CH, Hsieh KJ, et al., (2000). Cytotoxic effects of cantharidin on the growth of normal and cancer cells, Toxicology, 147: 77-87.
-  Wang KR, Zhang W, Yan JX, Li J, Wang R (2008). Antitumor effects, cell selectivity and structure activity relationship of a novel antimicrobial peptide of polybia MPI, Peptides, 29: 963-968.
-  Yang SH, Chien CM, Lu MC, et al., (2005). Cardiotoxin III induces apoptosis in K562 cells through a mitochondrialmediated pathway, Clin & Experimental Pharmacology & Physiology, 32: 515-20.
-  Yang SH, Chien CM, Lu MC, et al., (2006). Up-regulation of Bax and endonuclease G, and down-modulation of Bcl-XL involved in cardiotoxin III-induced apoptosis in K562 cells, Experimental & Molecular Med, 38: 435-44.
-  Yeh JY, Huang WJ, Kan SF, Wang PS (2003). Effects of bufalin and cinobufaginon the proliferation of androgen dependent and independent prostate cancer cells, Prostate, 54: 112.
-  Zheng LH, Bao YL, Wu Y et al., (2008). Cantharidin reverses multidrug resistance of human hepatoma HepG2/ADM cells via down –regulation of P-glycoprotein expression, Cancer Lett, 272: 102-109.
Publication order reference