[1] Escoubas P. Molecular diversification in spider venoms: a web  of combinatorial peptide libraries. Mol Divers 2006; 10:  545-554.

[2] Poornima P, Kumar JD, Zhao Q, Blunder M, Efferth T. Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature. Pharmacol Res 2016; 111: 290-302.

[3] Espinoza-Fonseca LM. The benefits of the multi-target approach in drug design and discovery. Bioorg Med Chem  2006;14: 896-897.

[4] Azmi AS, Mohammad RM. Rectifying cancer drug discovery  through network pharmacology. Future Med Chem 2014; 6:  529-139.

[5] Anighoro A, Bajorath J, Rastelli G. Polypharmacology: challenges and opportunities in drug discovery. J Med Chem 2014;  57: 7874-7887

[6] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674. [7] Heger M, van Golen RF, Broekgaarden M, Michel MC. The  molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer.  Pharmacol Rev 2013; 66: 222-307.

[8] Yu QT, Meng ZB. Treatment of advanced breast cancer with a  combination of highly agglutinative staphylococcin and vinorelbine-based chemotherapy. Eur Rev Med Pharmacol Sci  2016; 20: 3465-3468.

[9] Newman DJ, Cragg GM. Natural products as sources of new  drugs over the 30 years from 1981 to 2010. J Nat Prod 2012;  75: 311-335.

[10] Rodríguez de la Vega RC, Possani LD. Overview of scorpion  toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution. Toxicon 2005; 46: 831-844. 

[11] Zeng XC, Corzo G, Hahin R. Scorpion venom peptides without disulfide bridges. IUBMB Life 2005; 57: 13-21.

[12] Heinen TE, Veiga AB. Arthropod venoms and cancer. Toxicon  2011; 57: 497-511.

[13] Zhang FT, Xu ZS, Qi YX. A preliminary research of the  antineoplastic effects induced by Buthus martensii of Chinese  drug-I. Observation of the effect on mice with tumor. J Gannan Med Coll 1987; 6: 1-5. 

[14] Wang WX, Ji YH. Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro. J  Neurooncol 2005; 73: 1-7.

[15] Li W, Li Y, Zhao Y, Yuan J, Mao W. Inhibition effects of scorpion venom extracts (Buthus matensii Karsch) on the growth  of human breast cancer MCF-7 cells. Afr J Tradit Complement  Altern Med 2014; 11: 105-110. 

[16] Kim YT, Zhao M. Aberrant cell cycle regulation in cervical  carcinoma. Yonsei Med J 2005; 46(5): 597-613. 

[17] Tashiro E, Tsuchiya A, Imoto M. Functions of cyclin D1 as an  oncogene and regulation of cyclin D1 expression. Cancer Sci  2007; 98: 629-635.

[18] Gao F, Li H, Chen YD, Yu XN, Wang R, Chen XL. Upregula tion of PTEN involved in scorpion venom-induced apoptosis  in a lymphoma cell line. Leuk Lymphoma. 2009; 50: 633-641.

[19] Hers I, Vincent EE, Tavaré JM. Akt signaling in health and  disease. Cell Signal 2011; 23: 1515-1527. 

[20] Hambardzumyan D, Becher OJ, Holland EC. Cancer stem  cells and survival pathways. Cell Cycle 2008; 7: 1371- 1378.

[21] Wang X, Wang Z, Zhang Y, Jia Q, Wang Z, Zhang J, Zhang W.  Mechanisms for inhibition effects of polypeptide extract from scorpion venom (PESV) on proliferation of A549 cell lines in  vitro. Zhongguo Zhong Yao Za Zhi 2012; 37: 1620-1623.

[22] Zhao QQ, Zhang WD, Wu LC, Zhang LL, Wang ZP, Zhang  YY, Wang ZX, Jia Q. Mechanism of Polypeptide Extract from Scorpion Venom Combined Rapamycin in Enhancing Au tophagy of H22 Hepatoma Cells: an Experimental Study.  Zhongguo Zhong Xi Yi Jie He Za Zhi 2015; 35: 866-870.

[23] Yu WJ, Yang WH, Yang XD, Shi ZX, Wang XL, Hao Z,  Zhang J. Influence of polypeptide extract from scorpion ven- Rapôso | Journal of Clinical and Translational Research 2017; 3(2): 233-249 247 Distributed under creative commons license 4.0 DOI: http://dx.doi.org/10.18053/jctres.03.201702.002 om on PI3K and p-Akt signaling protein expression and cell  proliferation of K562 cells. Zhongguo Shi Yan Xue Ye Xue Za  Zhi 2012; 20: 872-875.

[24] Sui WW, Zhang WD, Wu LC, Zhang YY, Wang ZP, Wang ZX,  Jia Q. Study on the mechanism of polypeptide extract from  scorpion venom on inhibition of angiogenesis of H 22 hepatoma. Zhongguo Zhong Xi Yi Jie He Za Zhi 2014; 34:  581-586.

[25] Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 2011; 30: 87.

[26] Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G.  Rang & Dale’s Pharmacologia, 7th ed. Rio de Janeiro: Elsevier Inc 2012; 778 p. 

[27] Tong-ngam P, Roytrakul S, Sritanaudomchai H. BmKn-2 scorpion venom peptide for killing oral cancer cells by apoptosis. Asian Pac J Cancer Prev 2015; 16: 2807-2811.

[28] Satitmanwiwat S, Changsangfa C, Khanuengthong A,  Promthep K, Roytrakul S, Arpornsuwan T, Saikhun K, Sritanaudomchai H. The scorpion venom peptide BmKn2 induces  apoptosis in cancerous but not in normal human oral cells.  Biomed Pharmacother 2016; 84: 1042-1050.

[29] Li W, Xin Y, Chen Y, Li X, Zhang C, Bai J, Yuan J. The anti-proliferative effects and mechanisms of low molecular  weight scorpion BmK venom peptides on human hepatoma  and cervical carcinoma cells in vitro. Oncol Lett 2014; 8:  1581-1584.

[30] Salem ML, Shoukry NM, Teleb WK, Abdel-Daim MM, Abdel-Rahman MA. In vitro and in vivo antitumor effects of the  Egyptian scorpion Androctonus amoreuxi venom in an Ehrlich  ascites tumor model. SpringerPlus 2016; 5: 570

[31] Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest. Exp Mol Pathol 2011; 91: 447-454.

[32] Caliskan F, Ergene E, Sogut I, Hatipoglu I, Basalp A, Sivas H,  Kanbak G. Biological assays on the effects of Acra3 peptide  from Turkish scorpion Androctonus crassicauda venom on a  mouse brain tumor cell line (BC3H1) and production of specific monoclonal antibodies. Toxicon 2013; 76: 350-361. 

[33] Gupta S, Debnath A, Saha A, Giri B, Tripathi G, Vedasiromoni  JR, Gomes A, Gomes A. Indian black scorpion (Heterometrus  bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and  K562. Leuk Res 2007; 31: 817-825. 

[34] Gupta SD, Gomes A, Debnath A, Saha A, Gomes A. 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 2010; 183: 293-303.

[35] D’Suze G, Rosales A, Salazar V, Sevcik C. Apoptogenic peptides from Tityus discrepans scorpion venom acting against  the SKBR3 breast cancer cell line. Toxicon 2010; 56:  1497-1505.

[36] Reshkin SJ, Bellizzi A, Cardone RA, Tommasino M, Casavola  V, Paradiso A. Paclitaxel induces apoptosis via protein kinase  A- and p38 mitogen-activated protein-dependent inhibition of  the Na+/H+ exchanger (NHE) NHE isoform 1 in human  breast cancer cells. Clin Cancer Res 2003; 9: 2366-2373.

[37] Friesen C, Herr I, Krammer PH, Debatin KM. Involvement of  the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat Med 1996; 2: 574- 577.

[38] Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells. Mol Cell  Biochem 2011; 348: 173-181.

[39] Zargan J, Umar S, Sajad M, Naime M, Ali S, Khan HA. Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population  in human breast cancer cells (MCF-7). Toxicol In Vitro 2011;  25: 1748-1756.

[40] Díaz-García A, Morier-Díaz L, Frión-Herrera Y, RodríguezSánchez H, Caballero-Lorenzo Y, Mendoza-Llanes D, Riquenes-Garlobo Y, Fraga-Castro JA. In vitro anticancer effect of  venom from Cuban scorpion Rhopalurus junceus against a  panel of human cancer cell lines. J Venom Res 2013; 4: 5-12

[41] Knudson AG, Jr. Genetics of human cancer. Annu Rev Genet  1986; 20: 231-251. 

[42] Attardi LD, Jacks T. The role of p53 in tumor suppression:  lessons from mouse models. Cell Mol Life Sci 1999; 55:  48-63.

[43] DeBin JA, Maggio JE, Strichartz GR. Purification and characteri

[44] zation of chlorotoxin, a chloride channel ligand from the  venom of the scorpion. Am J Physiol 1993; 264: C361- 369.

45] Xu T, Fan Z, Li W, Dietel B, Wu Y, Beckmann MW, Wrosch  JK, Buchfelder M, Eyupoglu IY, Cao Z, Savaskan NE. Identification of two novel Chlorotoxin derivatives CA4 and  CTX-23 with chemotherapeutic and anti-angiogenic potential.  Sci Rep 2016; 6: 19799.

[46] Al-Asmari AK, Islam M, Al-Zahrani AM. In vitro analysis of  the anticancer properties of scorpion venom in colorectal and  breast cancer cell lines. Oncol Lett 2016; 11: 1256-1262.

[47] Tatti O, Gucciardo E, Pekkonen P, Holopainen T, Louhimo R, Repo P, Maliniemi P, Lohi J, Rantanen V, Hautaniemi S,  Alitalo K, Ranki A, Ojala PM, Keski-Oja J, Lehti K. MMP16  Mediates a Proteolytic Switch to Promote Cell-Cell Adhesion,  Collagen Alignment, and Lymphatic Invasion in Melanoma.  Cancer Res 2015; 75: 2083-2094.

[48] Deshane J, Garner CC, Sontheimer H. Chlorotoxin inhibits  glioma cell invasion via matrix metalloproteinase-2. J Biol  Chem 2003; 278: 4135-4144. 

[49] El-Ghlban S, Kasai T, Shigehiro T, Yin HX, Sekhar S, Ida M,  Sanchez A, Mizutani A, Kudoh T, Murakami H, Seno M.  Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells. Biomed Res Int 2014; 2014: 152659.

[50] Qin C, He B, Dai W, Lin Z, Zhang H, Wang X, Wang J, Zhang  X, Wang G, Yin L, Zhang Q. The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3. Biomaterials 2014; 35:  5908-5920.

[51] Qin C, He B, Dai W, Zhang H, Wang X, Wang J, Zhang X,  Wang G, Yin L, Zhang Q. Inhibition of metastatic tumor  growth and metastasis via targeting metastatic breast cancer  by chlorotoxin-modified liposomes. Mol Pharm 2014; 11:  3233-3241.

[52] Wu JJ, Dai L, Lan ZD, Chi CW. The gene cloning and sequencing of BM-12, a chlorotoxin-like peptide from the scorpion Buthus martensi Karsch. Toxicon 2000; 38: 661-668.

[53] Zeng XC, Li WX, Zhu SY, Peng F, Zhu ZH, Wu KL, Yiang  FH. Cloning and characterization of a cDNA sequence encoding the precursor of a chlorotoxin-like peptide from the Chinese scorpion Buthus martensii Karsch. Toxicon 2000; 38:  1009-1014.

[54] Fu YJ, Yin LT, Liang AH, Zhang CF, Wang W, Chai BF, et al.  Therapeutic potential of chlorotoxin-like neurotoxin from the  Chinese scorpion for human gliomas. Neurosci Lett 2007; 412:  62-67.

Fu YJ, An N, Chan KG, Wu, YB, Zheng SH, Liang AH. A  model of BmK CT in inhibiting glioma cell migration via matrix metalloproteinase-2 from experimental and molecular dynamics simulation study. Biotechnol Lett 2011; 33:  1309-1317

[56] Du J, Fu Y, Wang J, Liang A. Adenovirus-mediated expression  of BmK CT suppresses growth and invasion of rat C6 glioma  cells. Biotechnol Lett 2013; 35: 861-870. 

[57] Zhao Y, Cai X, Ye T, Huo J, Liu C, Zhang S, Cao P. Analgesic-antitumor peptide inhibits proliferation and migration of SHG-44 human malignant glioma cells. J Cell Biochem 2011;  112: 2424-2434. 

[58] Ernest NJ, Weaver AK, Van Duyn LB, Sontheimer HW. Relative contribution of chloride channels and transporters to regulatory volume decrease in human glioma cells. Am J Physiol  Cell Physiol 2005; 288: C1451-C1460. 

[59] Fioretti B, Castigli E, Micheli MR, Bova R, Sciaccaluga M,  Harper A, Franciolini F, Catacuzzeno L. Expression and modulation of the intermediate-conductance Ca2-activated K channel in glioblastoma GL-15 cells. Cell Physiol Biochem  2006; 18: 47-56.

[60] Bai H, Chen G, Fang C, Yang X, Yu S, Hai C. Osteosarcoma  cell proliferation and migration are partly regulated by redox-activated NHE-1. J Clin Tranl Res 2015; 1: 168-179.

[61] Ransom CB, O’Neal JT, Sontheimer H. Volume-activated  chloride currents contribute to the resting conductance and  invasive migration of human glioma cells. J Neurosci 2001;  21: 7674-7683. 

[62] McFerrin MB, Sontheimer H. A role for ion channels in glioma cell invasion. Neuron Glia Biol 2006; 2: 39-49.

[63] Possani LD, Becerril B, Delepierre M, Tytgat J. Scorpion  toxins specific for Na+-channels. Eur J Biochem 1999; 264(2):  287-300.

[64] Batista CV, Gomez-Lagunas F, Rodriguez de la Vega RC,  Hajdu P, Panyi G, Gáspar R, Possani LD. Two novel toxins  from the Amazonian scorpion Tityus cambridgei that block  Kv1.3 and Shaker B K(+)-channels with distinctly different  affinities. Biochim Biophys Acta 2002; 1601: 123-131. 

[65] Ullrich N, Gillespie GY, Sontheimer H. Human astrocytoma  cells express a unique chloride current. Neuroreport 1996; 7:  1020-1024.

[66] Barhanin J, Pauron D, Lombet A, Norman RI, Vijverberg HP,  Giglio JR, Lazdunski M. Electrophysiological characterization,  solubilization and purification of the Titius gamma toxin receptor associated with the gating component of the Na+  channel from rat brain. EMBO J 1983; 2: 915-920.

[67] Kirsch GE, Skattebøl A, Possani LD, Brown AM. Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus. J Gen Physiol 1989; 93: 67-83.

[68] Guo X, Ma C, Du Q, Wei R, Wang L, Zhou M, Chen T, Shaw  C. Two peptides, TsAP-1 and TsAP-2, from the venom of the  Brazilian yellow scorpion, Tityus serrulatus: evaluation of  their antimicrobial and anticancer activities. Biochimie 2013;  95:1784-1794. 

[69] Won A, Ruscito A, Ianoul A. Imaging the membrane lytic  activity of bioactive peptide latarcin 2a. Biochim Biophys Acta 2012; 1818: 3072-3080. 

[70] Habela CW, Ernest NJ, Swindall AF, Sontheimer H. Chloride  accumulation drives volume dynamics underlying cell proliferation and migration. J Neurophysiol 2008; 101: 750-757.

[71] Haas BR, Sontheimer H. Inhibition of the Sodium-Potassium-Chloride Cotransporter Isoform-1 reduces glioma invasion. Cancer Res 2010; 70: 5597-5606.

[72] Zhao L, Zhu J, Cheng Y, Xiong Z, Tang Y, Guo L, Shi X,  Zhao J. Chlorotoxin-conjugated multifunctional dendrimers  labeled with radionuclide 131I for single photon emission  computed tomography imaging and radiotherapy of gliomas.  ACS Appl Mater Interfaces 2015; 7: 19798-19808.

[73] Wu XS, Jian XC, Yin B, He ZJ. Development of the research  on the application of chlorotoxin in imaging diagnostics and  targeted therapies for tumors. Chin J Cancer 2010; 29:  626-630.

[74] Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A,  Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez  VL, Gonda MA. Phase I single-dose study of intracavitaryadministered iodine-131-TM-601 in adults with recurrent  high-grade glioma. J Clin Oncol 2006; 24: 3644-3650.

[75] Fink K, Mamelak A, Rosenfeld S, Drappatz J, Wen P, Olson J,  Wahl R, Jacene H, Omuno A, Pan E, Grimm S, Raizer J, Mobile N, Chamberlain M, Zhu JJ, Fiveash J, Schiff D, Edgeworth M, Malkin M, Mrugala M, Chmura S, Gribbin T. A  phase 1/2 multi-center, safety and efficacy study evaluating  intravenously administered 131I-TM601 in patients with progressive and/or recurrent malignant glioma. ClinicalTrials.gov  Identifier: NCT00683761. https://clinicaltrials.gov/ct2/show/  NCT00683761 and http://adisinsight.springer.com/trials/  700034613. 

[76] Fan S, Sun Z, Jiang D, Dai C, Ma Y, Zhao Z, Liu H, Wu Y,  Cao Z, Li W. BmKCT toxin inhibits glioma proliferation and  tumor metastasis. Cancer Lett 2010; 291: 158-166.

[77] Huang L, Li B, Li W, Guo H, Zou F. ATP-sensitive potassium  channels control glioma cells proliferation by regulating ERK  activity. Carcinogenesis 2009; 30: 737-744.

[78] Ru Q, Tian X, Wu YX, Wu RH, Pi MS, Li CY. Voltage-gated  and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma. Oncol Rep 2014;  31: 842-848. 

[79] Ma J, Hu Y, Guo M, Huang Z, Li W, Wu Y. hERG potassium  channel blockage by scorpion toxin BmKKx2 enhances  erythroid differentiation of human leukemia cells K562. PLoS  One 2013; 8: e84903.

[80] Hietakangas V, Poukkula M, Heiskanen KM, Karvinen JT,  Sistonen L, Eriksson JE. Erythroid differentiation sensitizes  K562 leukemia cells to TRAIL-induced apoptosis by downregulation of c-FLIP. Mol Cell Biol 2003; 23: 1278-1291.

[81] Pineda SS, Undheim EA, Rupasinghe DB, Ikonomopoulou  MP, King GF. Spider venomics: implications for drug discovery. Future Med Chem 2014; 6: 1699-1714. 

[82] Jenssen H, Hamill P, Hancock RE. Peptide antimicrobial  agents. Clin Microbiol Rev 2006; 19: 491-511.

[83] Dubovskii PV, Vassilevski AA, Kozlov SA, Feofanov AV, Grishin EV, Efremov RG. Latarcins: versatile spider venom  peptides. Cell Mol Life Sci 2015; 72: 4501-4522. 

[84] Vorontsova OV, Egorova NS, Arseniev AS, Feofanov AV.  Haemolytic and cytotoxic action of latarcin Ltc2a. Biochimie  2011; 93: 227-241.

[85] Liu Z, Deng M, Xiang J, Ma H, Hu W, Zhao Y, Li DW, Liang  S. A novel spider peptide toxin suppresses tumor growth  through dual signaling pathways. Curr Mol Med 2012; 12:  1350-1360. 

[86] Liu Z, Zhao Y, Li J, Xu S, Liu C, Zhu Y, Liang S. The venom  of the spider Macrothele raveni induces apoptosis in the myelogenous leukemia K562 cell line. Leuk Res 2012; 36: 1063- 1066. 

[87] Gao L, Yu S,Wu Y, Shan B. Effect of spider venom on cell  apoptosis and necrosis rates in MCF-7 cells. DNA Cell Biol  2007; 26: 485-489.

[88] Gao L, Feng W, Shan BE, Zhu BC. Inhibitory effect of the  venom of spider Macrothele raveni on proliferation of human  hepatocellular carcinoma cell line BEL-7402 and its mechanism. Ai Zheng 2005; 24: 812-816

[89] Gao L, Shan BE, Chen J, Liu JH, Song DX, Zhu BC. Effects of spider Macrothele raven venom on cell proliferation and  cytotoxicity in HeLa cells. Acta Pharmacol Sin 2005; 26:  369-376.

[90] Gomez MV, Kalapothakis E, Guatimosim C, Prado MA. Phoneutria nigriventer venom: a cocktail of toxins that affect ion  channels. Cell Mol Neurobiol 2002; 22: 579-588. 

[91] Rigo FK, Trevisan G, Rosa F, Dalmolin GD, Otuki MF, Cueto  AP, Castro Junior CJ, Romano-Silva MA, Cordeiro MN,  Richardson M, Ferreira J, Gomez MV. Spider peptide Phα1β  induces analgesic effect in a model of cancer pain. Cancer Sci  2013; 104: 1226-1230. 

[92] Le Sueur L, Kalapothakis E, Cruz-Höfling MA. Breakdown of  the blood-brain barrier and neuropathological changes induced  by Phoneutria nigriventer spider venom. Acta Neuropathol  2003; 105: 125-134. 

[93] Rapôso C, Zago GM, Silva GH, Cruz-Höfling MA. Acute  blood-brain barrier permeabilization in rats after systemic  Phoneutria nigriventer venom. Brain Res 2007; 1149: 18-29. 

[94] Rapôso C, Odorissi PA, Oliveira AL, Aoyama H, Ferreira CV,  Verinaud L, Fontana K, Ruela-de-Sousa RR, Cruz-Höfling  MA. Effect of Phoneutria nigriventer venom on the expression  of junctional protein and P-gp efflux pump function in the  blood-brain barrier. Neurochem Res 2012; 37: 1967-1981. 

[95] Rapôso C, Odorissi PA, Savioli SF, Hell RC, Simões GF,  Ruela-de-Sousa RR, Oliveira AL, Cruz-Höfling MA. Triggering of protection mechanism against Phoneutria nigriventer  spider venom in the brain. PLoS One 2014; 9: e107292.

[96] Cruz-Höfling MA, Tavares JC, Rapôso C. Phoneutria nigriventer venom: Action in the central nervous system. In: Gopalakrishnakone P, Corzo G, Lima ME, Dego-García E, editors.  Spider Venoms, Toxinology series. Netherlands: Springer  2015; 175-202. 

[97] Cruz-Höfling MA, Rapôso C, Verinaud L, Zago GM. Neuroinflammation and astrocytic reaction in the course of Phoneutria nigriventer (armed-spider) blood-brain barrier (BBB)  opening. Neurotoxicol 2009; 30: 636-646. 

[98] Stávale LM, Soares ES, Mendonça MC, Irazusta SP, CruzHöfling MA. Temporal relationship between aquaporin-4 and  glial fibrillary acidic protein in cerebellum of neonate and  adult rats administered a BBB disrupting spider venom. Toxicon 2013; 66: 37-46. 

[99] Rapôso C, Björklund U, Kalapothakis E, Biber B, CruzHöfling MA, Hansson E. Neuropharmacological effects of  Phoneutria nigriventer venom on astrocytes. Neurochem Int  2016; 96: 13-23

[100] Einbond LS, Shimizu M, Ma H, Wu HA, Goldsberry S, Sicular S, Panijikaran M, Genovese G, Cruz E. Actein inhibits the  Na+-K+-ATPase and enhances the growth inhibitory effect of  digitoxin on human breast cancer cells. Biochem Biophys Res  Commun 2008; 375: 608-613.

[101] Castro MG, Candolfi M, Kroeger K, King GD, Curtin F, Yagiz  K, Mineharu Y, Assi H, Wibowo M, Ghulam Muhammad AK,  Foulad D, Puntel M, Lowenstein PR. Gene therapy and targeted toxins for glioma. Curr Gene Ther 2011; 11: 155-180.

[102] Choene M, Motadi L. Validation of the antiproliferative effects of Euphorbia tirucalli extracts in breast cancer cell lines.  Mol Biol (Mosk) 2016; 50: 115-127.

[103] Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nat Rev Drug Discov 2003; 2: 790-802.

[104] Caramori CA, Barraviera B. Universities and neglected diseases – it is not enough to have the knowledge, it must be applied. J Venom Anim Toxins Incl Trop Dis 2011; 17: 1-3

[105] Guimarães R. Pesquisa Translacional: uma interpretação.  Ciênc saúde coletiva 2013; 18: 1731-1744. 

[106] Barraviera B. How to overcome the gap between basic research and clinical trials? J Venom Anim Toxins Incl Trop Dis  2011; 17: 361.

[107] Fujita K, Iwama H, oura K, Tadakoro T, Samukawa E, Sakamoto T, Nomura T, Tani J, Yoneyama H, Morishita A,  Himoto T, Hirashima M, Masaki T. Cancer therapy due to  apoptosis: galectin-9. Int J Mol Sci 2017; 18: E74. 

[108] Zhao W, Qiu Y, Kong D. Class I phosphatidylinositol 3-kinase  inhibitors for cancer therapy. Acta Pharm Sin B 2017; 7(1):  27-37. 

[109] Ranjan A, Iwakuma T. Non-canonical cell death induced by p53. Int J Mol Sci 2016; 17: E2068. 

[110] Litan A, Langhans SA. Cancer as a channelopathy: ion channels and pumps in tumor development and progression. Front  Cell Neurosci 2015; 9: 86.