Cancer Chemotherapy and Pharmacology

, Volume 80, Issue 5, pp 919–924 | Cite as

Animals living in polluted environments are a potential source of anti-tumor molecule(s)

  • Shareni Jeyamogan
  • Naveed Ahmed Khan
  • Ruqaiyyah Siddiqui
Review Article

Abstract

Despite advances in therapeutic interventions and supportive care, the morbidity and mortality associated with cancer have remained significant. Thus, there is a need for newer and more powerful anti-tumor agents. The search for new anti-tumor compounds originating from natural resources is a promising research area. Animals living in polluted environments are a potent source of anti-tumor agents. Under polluted milieus, species such as crocodiles, feed on rotten meat, are exposed to heavy metals, endure high levels of radiation, and are among the very few species to survive the catastrophic Cretaceous-Tertiary extinction event with a prolonged lifespan. Thus, it is reasonable to speculate that animals such as crocodiles have developed mechanisms to defend themselves against cancer. The discovery of antitumor activity in animals such as crocodiles, whales, sharks, etc. will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor compound(s) that may also overcome current drug resistance. Nevertheless, intensive research in the next few years will be required to realize these expectations.

Keywords

Anticancer agents Animals-based compounds Cancer resistance Antitumor molecule(s) 

Notes

Compliance with ethical standards

Conflict of interest

SJ declares that she has no conflict of interest. NAK declares that he has no conflict of interest. RS declares that she has no conflict of interest.

Funding

This study was funded by Sunway University, Malaysia, grant FST-2015-05.

Ethical approval

This article does not contain any studies with human participants and animals performed by any of the authors.

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Can 136:359–386CrossRefGoogle Scholar
  2. 2.
    Global Cancer facts and figures (2017) American Cancer Society. https://www.cancer.org/research/cancer-facts-statistics/global.html. Accessed 10 Jan 2017
  3. 3.
    Rolston KVI (2017) Infections in cancer patients with solid tumors: a review. Infect Dis Ther. doi: 10.1007/s40121-017-0146-1 (epub ahead of print) PubMedPubMedCentralGoogle Scholar
  4. 4.
    Ehrhardt H, Pannert L, Pfeiffer S, Wachter F, Amtmann E, Jeremias I (2013) Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies. Br J Pharmacol 168:1558–1569CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kang K, Oh SH, Yun JH, Jho EH, Kang JH, Batsuren D, Tunsag J, Park KH, Kim M, Nho CW (2011) A novel topoisomerase inhibitor, Daurinol, suppresses growth of HCT116 cells with low hematological toxicity compared to etoposide. Neoplasia 13:1043IN26–1057IN30CrossRefGoogle Scholar
  6. 6.
    Kampan NC, Madondo MT, McNally OM, Quinn M, Plebanski M (2015) Paclitaxel and its evolving role in the management of ovarian cancer. Biomed Res Int 2015:1–25CrossRefGoogle Scholar
  7. 7.
    Siddiqui R, Mansur S, Khan NA (2016) Do crocodiles and alligators hold the key to treat cancer? BMJ 354:i3763CrossRefGoogle Scholar
  8. 8.
    Lehner AF, Rumbeiha W, Shlosberg A, Stuart K, Johnson M, Domenech R, Langner H (2013) Diagnostic analysis of veterinary dried blood spots for toxic heavy metals exposure. ‎J Anal Toxicol 37:406–422CrossRefPubMedGoogle Scholar
  9. 9.
    Schneider L, Peleja RP, Kluczkovski A, Freire GM, Marioni B, Vogt PC, Da Silveira R (2012) Mercury concentration in the spectacled caiman and black caiman (Alligatoridae) of the Amazon: implications for human health. Arch Environ Contam Toxicol 63:270–279CrossRefPubMedGoogle Scholar
  10. 10.
    Rainwater TR, Millichamp NJ, Barrantes ID, Barr BR, Montero JR, Platt SG, Abel MT, Cobb GP, Anderson TA (2011) Ocular disease in American crocodiles (Crocodylus acutus) in Costa Rica. J Wildl Dis 47:415–426CrossRefPubMedGoogle Scholar
  11. 11.
    Vieira LM, Nunes Vda S, Amaral MC, Oliveira AC, Hauser-Davis RA, Campos RC (2010) Mercury and methyl mercury ratios in caimans (Caiman crocodilus yacare) from the Pantanal area Brazil. J Environ Monitor 13:280–287CrossRefGoogle Scholar
  12. 12.
    Campbell JW, Waters MN, Tarter A, Jackson J (2010) Heavy metal and selenium concentrations in liver tissue from wild American alligator (Alligator mississippiensis) livers near Charleston, South Carolina. J Wildlife Dis 46:1234–1241CrossRefGoogle Scholar
  13. 13.
    Janke A, Gullberg A, Hughes S, Aggarwal RK, Arnason U (2005) Mitogenomic analyses place the gharial (Gavialis gangeticus) on the crocodile tree and provide pre-K/T divergence times for most crocodilians. J Mol Evol 61:620–626CrossRefPubMedGoogle Scholar
  14. 14.
    Colbert EH (1997) The age of reptiles. Generating Publishing Company (ISBN 0-486-29377-7)Google Scholar
  15. 15.
    Dietz J, Heckers KO, Aupperle H, Pees M (2016) Cutaneous and subcutaneous soft tissue tumours in snakes: a retrospective study of 33 cases. J Comp Pathol 155:76–87CrossRefPubMedGoogle Scholar
  16. 16.
    Eyarefe OD, Antia RE, Oguntoye CO, Abiola OO, Alaka OO, Ogunsola JO (2012) Rhabdomyosarcoma in a terrestrial tortoise (Geochelone nigra) in Nigeria: a case report. J South Afr Vet Assoc. doi: 10.4102/jsava.v83i1.300 Google Scholar
  17. 17.
    Janert B (1998) A fibrosarcoma in a Siamese crocodile (Crocodylus siamensis). J Zoo Wildlife Med 29:72–77Google Scholar
  18. 18.
    Martorell J, Ramis A, Espada Y (2002) Use of ultrasonography in the diagnosis of hepatic spindle-cell sarcoma in a savannah monitor (Varanus exanthematicus). Vet Rec 150:282–284CrossRefPubMedGoogle Scholar
  19. 19.
    Leone A, Dark M, Kondo H, Rotstein DS, Kiupel M, Walsh MT, Erlacher-Reid C, Gordon N, Conway JA (2013) Gastrointestinal leiomyosarcoma in a pygmy sperm whale (Kogia breviceps). J Zoo Wildlife Med 44:744–748CrossRefGoogle Scholar
  20. 20.
    Manire CA, Clarke AC, Wert D, Landolfi J (2013) Lymphosarcoma in a captive bonnethead shark, Sphyrna tiburo (L.). J Fish Dis 36:437–440CrossRefPubMedGoogle Scholar
  21. 21.
    Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ (2016) TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. eLife. doi: 10.7554/eLife.11994 (epub ahead of print) Google Scholar
  22. 22.
    Keane M, Semeiks J, Webb AE, Li Y, Quesada V, Craig T, Madsen LB, van Dam S, Brawand D, Marques PI, Michalak P, Kang L, Bhak J, Yim HS, Grishin NV, Nielsen NH, Heide-Jørgensen MP, Oziolor EM, Matson CW, Church GM, Stuart GW, Patton JC, George JC, Suydam R, Larsen K, López-Otín C, O’Connell MJ, Bickham JW, Thomsen B, de Magalhães JP (2015) Insights into the evolution of longevity from the bowhead whale genome. Cell Rep 10:112–122CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Abegglen LM, Caulin AF, Chan A, Lee K, Robinson R, Campbell MS, Kiso WK, Schmitt DL, Waddell PJ, Bhaskara S, Jensen ST, Maley CC, Schiffman JD (2015) Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA 314:1850–1860CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Patathananone S, Thammasirirak S, Daduang J, Gung CJ, Temsiripong Y, Daduang S (2016) Inhibition of HeLa cells metastasis by bioactive compounds in crocodile (Crocodylus siamensis) white blood cells extract. Environ Toxicol 31:1329–1336CrossRefPubMedGoogle Scholar
  25. 25.
    Patathananone S, Thammasirirak S, Daduang J, Chung JG, Temsiripong Y, Daduang S (2016) Bioactive compounds from crocodile (Crocodylus siamensis) white blood cells induced apoptotic cell death in hela cells. Environ Toxicol 31:986–997CrossRefPubMedGoogle Scholar
  26. 26.
    Theansongnoen T, Maijaroen S, Jangpromma N, Yaraksa N, Daduang S, Temsiripong T, Daduang J, Klaynongsruang S (2016) Cationic Antimicrobial peptides derived from Crocodylus siamensis leukocyte extract, revealing anticancer activity and apoptotic induction on human cervical cancer cells. Protein J 35:202–211CrossRefGoogle Scholar
  27. 27.
    Song W, Shen DY, Kang JH, Li SS, Zhan HW, Shi Y, Xiong YX, Liang G, Chen QX (2012) Apoptosis of human cholangiocarcinoma cells induced by ESC-3 from Crocodylus siamensis bile. World J Gastroenterol 18:704–711CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wang DQ, Carey MC (2014) Therapeutic uses of animal biles in traditional Chinese medicine: an ethnopharmacological, biophysical chemical and medicinal review. World J Gastroenterol 20:9952–9975CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kang JH, Zhang WQ, Song W, Shen DY, Li SS, Tian L, Shi Y, Liang G, Xiong YX, Chen QX (2012) Apoptosis mechanism of human cholangiocarcinoma cells induced by bile extract from crocodile. Appl Biochem Biotechnol 166:942–951CrossRefPubMedGoogle Scholar
  30. 30.
    Song W, Li SS, Qiu PP, Shen DY, Tian L, Zhang QY, Liao LX, Chen QX (2013) apoptosis induced by aqueous extracts of crocodile bile in human heptacarcinoma SMMC-7721. Appl Biochem Biotechnol 170:15–24CrossRefPubMedGoogle Scholar
  31. 31.
    Shen DY, Zhang W, Zeng X, Liu CQ (2013) Inhibition of Wnt⁄b-catenin signaling downregulates P-glycoprotein and reverses multi-drug resistance of cholangiocarcinoma. JCA 104:1303–1308Google Scholar
  32. 32.
    Albert DS, Martinez ME, Hess LM, Einspahr JG, Green SB, Bhattacharyya AK, Guillen J, Krutzsch M, Batta AK, Salen G, Fales L, Koonce K, Parish D, Clouser M, Roe D, Lance P (2005) Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. J Natl Cancer Inst 97:846–853CrossRefGoogle Scholar
  33. 33.
    Ajouz H, Mukherji D, Shamseddine A (2014) Secondary bile acids: an underrecognized cause of colon cancer. World J Surg Oncol. doi: 10.1186/1477-7819-12-164 (epub ahead of print) PubMedPubMedCentralGoogle Scholar
  34. 34.
    Chaisakul J, Hodgson WC, Kuruppu S, Prasongsook N (2016) Effects of animal venoms and toxins on hallmarks of cancer. J Ca 7:1571–1578Google Scholar
  35. 35.
    Azevedo FV, Lopes DS, Cirilo Gimenes SN, Achê DC, Vecchi L, Alves PT, Guimarães Dde O, Rodrigues RS, Goulart LR, Rodrigues Vde M, Yoneyama KA (2016) Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom. Int J Biol Macromolec 82:671–677CrossRefGoogle Scholar
  36. 36.
    Bazaa A, Luis J, Srairi-Abid N, Kallech-Ziri O, Kessentini-Zouari R, Defilles C, Lissitzky JC, El Ayeb M, Marrakchi N (2009) MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration. Matrix Biol 28:188–193CrossRefPubMedGoogle Scholar
  37. 37.
    Ebrahim K, Shirazi FH, Mirakabadi AZ, Vatanpour H (2015) Cobra venom cytotoxins; apoptotic or necrotic agents? Toxicon 108:134–140CrossRefPubMedGoogle Scholar
  38. 38.
    Tsai PC, Chu CL, Chiu CC, Chang LS, Lin SR (2014) Cardiotoxin III suppresses hepatocyte growth factor-stimulated migration and invasion of MDA-MB-231 cells. ‎Cell Biochem Funct 32:485–495CrossRefPubMedGoogle Scholar
  39. 39.
    Ding XL, Man YN, Hao J, Zhu CH, Liu C, Yang X, Wu XZ (2016) The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis. Biomed Res Int. doi: 10.1155/2016/7396392 (epub ahead of print) Google Scholar
  40. 40.
    Keane M, Craig T, Alföldi J, Berlin AM, Johnson J, Seluanov A, Gorbunova V, Di Palma F, Lindblad-Toh K, Church GM, de Magalhães JP (2014) The naked mole rat genome resource: facilitating analyses of cancer and longevity-related adaptations. Bioinformatics 30:3558–3560CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, Mao Z, Nevo E, Gorbunova V, Seluanov A (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499(7458):346–349CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Amiri A, Namavari M, Rashidi M, Fahmidekhar MA, Seghatoleslam A (2015) Inhibitory effects of Cyrtopodion scabrum extract on growth of human breast and colorectal cancer cells. APJCP 16:565–570PubMedGoogle Scholar
  43. 43.
    Zhang SX, Zhu C, Ba Y, Chen D, Zhou XL, Cao R, Wang LP, Ren Y, Wu XZ (2012) Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor. J Biol Chem 287:13206–13215CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Jiang JJ, Cheng LH, Wu H, He YH, Kong QP (2016) Insights into long noncoding RNAs of naked mole rat (Heterocephalus glaber) and their potential association with cancer resistance. Epigenetics Chromatin 9:1–10CrossRefGoogle Scholar
  45. 45.
    Piersigilli A, Meyerholz DK (2016) The ‘‘Naked Truth’’: naked mole-rats do get cancer. Vet Pathol 53:519–520CrossRefPubMedGoogle Scholar
  46. 46.
    Tian X, Azpurua J, Ke Z, Augereau A, Zhang ZD, Vijg J, Gladyshev VN, Gorbunova V, Seluanov A (2014) INK4 locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform. PNAS 112:1053–1058CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Taylor KR, Milone NA, Rodriguez CE (2017) four cases of spontaneous neoplasia in the naked molerat (Heterocephalus glaber), a putative cancer-resistant species. J Gerontol A Bio Sci 72:38–43CrossRefGoogle Scholar
  48. 48.
    Gonzales JA, Amich F, Postigo-Mota S, Vallejo JR (2016) The use of wild vertebrates in contemporary Spanish ethno veterinary medicine. J Ethnopharmacol 191:135–151CrossRefGoogle Scholar
  49. 49.
    Rodriguez C, Rollins-Smith L, Ibanez R, Durant-Archibold AA, Gutierrez M (2016) Toxins and pharmacologically active compounds from species of the family Bufonidae (Amphibia, Anura). J Ethnopharmacol. doi: 10.1016/j.jep.2016.12.021 (epub ahead of print) Google Scholar
  50. 50.
    Cruz e Carvalho A, Márquez CA, Azevedo RB, Joanitti GA, Pires Júnior OR, Fontes W, Castro MS (2015) Cytotoxic activity and antiproliferative effects of crude skin secretion from Physalaemus nattereri (Anura: Leptodactylidae) on in vitro melanoma cells. Toxins 7:3989–4005CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Liu Y, Ban LY, Su X, Gao S, Liu JW, Cui XN (2015) Effects of cinobufacini injection on cell proliferation and the expression of topoisomerases in human HepG-2 hepatocellular carcinoma cells. Mol Med Rep 12:1598–1604CrossRefPubMedGoogle Scholar
  52. 52.
    Nakata M, Mori S, Kamoshida Y, Kawaguchi S, Fujita-Yamaguchi Y, Gao B, Tang W (2015) Toad skin extract cinobufatini inhibits migration of human breast carcinoma MDA-MB-231 cells into a model stromal tissue. Biosci Trends 9:266–269CrossRefPubMedGoogle Scholar
  53. 53.
    Qi F, Inagaki Y, Kokudo N, Tamura S, Nakata M, Tang W (2011) Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Inter Pharmacol 11:342–349Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Shareni Jeyamogan
    • 1
  • Naveed Ahmed Khan
    • 1
  • Ruqaiyyah Siddiqui
    • 1
  1. 1.Department of Biological Sciences, School of Science and TechnologySunway UniversitySelangorMalaysia

Personalised recommendations