Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Sera/Organ Lysates of Selected Animals Living in Polluted Environments Exhibit Cytotoxicity against Cancer Cell Lines

Author(s): Shareni Jeyamogan, Naveed A. Khan*, Kuppusamy Sagathevan and Ruqaiyyah Siddiqui

Volume 19, Issue 18, 2019

Page: [2251 - 2268] Pages: 18

DOI: 10.2174/1871520619666191011161314

Price: $65

Abstract

Background: Species of crocodiles and cockroaches can withstand high radiation, reside in unsanitary conditions, thrive on germ-infested feed, and are exposed to heavy metals, yet they are not reported to develop cancer. It has been postulated that such species have mechanisms to defend themselves against developing cancer. Here, selected species have been tested for potential cytotoxicity against selected cancer cell lines.

Methods: In this study, various species of vertebrates and invertebrates were procured including Columba livia, Gallus gallus domesticus, Varanus salvator, Cuora kamamora amboinensis, Reticulatus malayanus, Oreochromis mossambicus, Rattus rattus, American bullfrog, Donax sp., Polymesoda coaxans, Tenebrio molitor, Lumbricus terrestris, Blatta lateralis, Grammostola rosea, and Penaeus monodon. Species were dissected and their organ lysates/sera/haemolymph were prepared. Cytotoxicity assays were performed using Prostate Cancer cells (PC3), Henrietta Lacks cervical adenocarcinoma cells (HeLa) and human breast adenocarcinoma cells (MCF7) as well as human keratinized skin cells (Hacat), by measuring lactate dehydrogenase release as an indicator for cell death. Growth inhibition assays were performed to determine the effects on cancer cell proliferation. Liquid Chromatography-Mass Spectrometry (LC-MS/MS) was performed for molecular identification.

Results: The results revealed that body lysates of Polymesoda coaxans demonstrated more than 99% growth inhibition of all cancer cell lines tested but not on normal Hacat cells. More importantly, the serum of M. reticulatus abolished growth and produced cytotoxicity. Hence these samples were subjected to Liquid Chromatography- Mass Spectrometry (LC-MS/MS), which detected 81 small molecules and putatively identified 20 molecules when matched against the METLIN database. Out of 1094 peptides, 21 peptides were identified, while 1074 peptides were categorized as novel peptides. Based on properties such as peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition, 306 potential peptides were identified.

Conclusion: To our knowledge, here for the first time, we report a comprehensive analysis of sera exhibiting cytotoxicity against cancer cell lines tested and identified several molecules using LC-MS/MS.

Keywords: Antitumor activity, Hela, Hacat, MCF7, PC3, polluted environment, cytotoxicity, growth inhibition.

Graphical Abstract
[1]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[2]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[3]
Siddiqui, R.; Mansur, S.; Khan, N.A. Do crocodiles and alligators hold the key to treat cancer? BMJ, 2016, 354, i3763.
[http://dx.doi.org/10.1136/bmj.i3763]
[4]
Sulak, M.; Fong, L.; Mika, K.; Chigurupati, S.; Yon, L.; Mongan, N.P.; Emes, R.D.; Lynch, V.J. TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. eLife, 2016, 5e11994
[http://dx.doi.org/10.7554/eLife.11994] [PMID: 27642012]
[5]
Keane, M.; Semeiks, J.; Webb, A.E.; Li, Y.I.; Quesada, V.; Craig, T.; Madsen, L.B.; van Dam, S.; Brawand, D.; Marques, P.I.; Michalak, P.; Kang, L.; Bhak, J.; Yim, H.S.; Grishin, N.V.; Nielsen, N.H.; Heide-Jørgensen, M.P.; Oziolor, E.M.; Matson, C.W.; Church, G.M.; Stuart, G.W.; Patton, J.C.; George, J.C.; Suydam, R.; Larsen, K.; López-Otín, C.; O’Connell, M.J.; Bickham, J.W.; Thomsen, B.; de Magalhães, J.P. Insights into the evolution of longevity from the bowhead whale genome. Cell Rep., 2015, 10(1), 112-122.
[http://dx.doi.org/10.1016/j.celrep.2014.12.008] [PMID: 25565328]
[6]
Abegglen, L.M.; Caulin, A.F.; Chan, A.; Lee, K.; Robinson, R.; Campbell, M.S.; Kiso, W.K.; Schmitt, D.L.; Waddell, P.J.; Bhaskara, S.; Jensen, S.T.; Maley, C.C.; Schiffman, J.D. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA, 2015, 314(17), 1850-1860.
[http://dx.doi.org/10.1001/jama.2015.13134] [PMID: 26447779]
[7]
Sagheer, M.; Siddiqui, R.; Iqbal, J.; Khan, N.A. Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities. Pathog. Glob. Health, 2014, 108(3), 129-136.
[http://dx.doi.org/10.1179/2047773214Y.0000000132] [PMID: 24625321]
[8]
Wang, Z.; Zhang, L.; Wan, Z.; He, Y.; Huang, H.; Xiang, H.; Wu, X.; Zhang, K.; Liu, Y.; Goodin, S.; Du, Z.; Zheng, X. Atorvastatin and caffeine in combination regulates apoptosis, migration, invasion and tumorspheres of prostate cancer cells. Pathol. Oncol. Res., 2018.
[http://dx.doi.org/10.1007/s12253-018-0415-7] [PMID: 29796873]
[9]
Khan, N.A.; Siddiqui, R. Acanthamoeba affects the integrity of human brain microvascular endothelial cells and degrades the tight junction proteins. Int. J. Parasitol., 2009, 39(14), 1611-1616.
[http://dx.doi.org/10.1016/j.ijpara.2009.06.004] [PMID: 19580812]
[10]
Jeyamogan, S.; Khan, N.A.; Siddiqui, R. Animals living in polluted environments are a potential source of anti-tumor molecule(s). Cancer Chemother. Pharmacol., 2017, 80(5), 919-924.
[http://dx.doi.org/10.1007/s00280-017-3410-x] [PMID: 28795217]
[11]
Siddiqui, R.; Jeyamogan, S.; Ali, S.M.; Abbas, F.; Sagathevan, K.A.; Khan, N.A. Crocodiles and alligators: Antiamoebic and antitumor compounds of crocodiles. Exp. Parasitol., 2017, 183, 194-200.
[http://dx.doi.org/10.1016/j.exppara.2017.09.008] [PMID: 28917711]
[12]
Ning, X.; Zhao, J.; Zhang, Y.; Cao, S.; Liu, M.; Ling, P.; Lin, X. A novel anti-tumor protein extracted from Meretrix meretrix Linnaeus induces cell death by increasing cell permeability and inhibiting tubulin polymerization. Int. J. Oncol., 2009, 35(4), 805-812.
[PMID: 19724916]
[13]
Wang, C.; Liu, M.; Cheng, L.; Wei, J.; Wu, N.; Zheng, L.; Lin, X. A novel polypeptide from Meretrix meretrix Linnaeus inhibits the growth of human lung adenocarcinoma. Exp. Biol. Med. (Maywood), 2012, 237(4), 442-450.
[http://dx.doi.org/10.1258/ebm.2012.011337] [PMID: 22522344]
[14]
Liu, M.; Zhao, X.; Zhao, J.; Xiao, L.; Liu, H.; Wang, C.; Cheng, L.; Wu, N.; Lin, X. Induction of apoptosis, G0/G1 phase arrest and microtubule disassembly in K562 leukemia cells by Mere15, a novel polypeptide from Meretrix meretrix Linnaeus. Mar. Drugs, 2012, 10(11), 2596-2607.
[http://dx.doi.org/10.3390/md10112596] [PMID: 23203280]
[15]
Song, E.J.; Chan, M.W.Y.; Shin, J.W.; Chen, C.C. Hard clam extracts induce atypical apoptosis in human gastric cancer cells. Exp. Ther. Med., 2017, 14(2), 1409-1418.
[http://dx.doi.org/10.3892/etm.2017.4630] [PMID: 28810604]
[16]
Soletti, R.C.; del Barrio, L.; Daffre, S.; Miranda, A.; Borges, H.L.; Moura-Neto, V.; Lopez, M.G.; Gabilan, N.H. Peptide gomesin triggers cell death through L-type channel calcium influx, MAPK/ERK, PKC and PI3K signaling and generation of reactive oxygen species. Chem. Biol. Interact., 2010, 186(2), 135-143.
[http://dx.doi.org/10.1016/j.cbi.2010.04.012] [PMID: 20433817]
[17]
Ge, G.F.; Yu, C.H.; Yu, B.; Shen, Z.H.; Zhang, D.L.; Wu, Q.F. Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker ethanol extract. J. Ethnopharmacol., 2012, 141(1), 178-182.
[http://dx.doi.org/10.1016/j.jep.2012.02.016] [PMID: 22366674]
[18]
Wang, F.X.; Wu, N.; Wei, J.T.; Liu, J.; Zhao, J.; Ji, A.G.; Lin, X.K. A novel protein from Eupolyphaga sinensis inhibits adhesion, migration, and invasion of human lung cancer A549 cells. Biochem. Cell Biol., 2013, 91(4), 244-251.
[http://dx.doi.org/10.1139/bcb-2013-0002] [PMID: 23859019]
[19]
Dai, B.; Qi, J.; Liu, R.; Zhang, Y. Eupolyphaga sinensis Walker demonstrates angiogenic activity and inhibits A549 cell growth by targeting the KDR signaling pathway. Mol. Med. Rep., 2014, 10(3), 1590-1596.
[http://dx.doi.org/10.3892/mmr.2014.2387] [PMID: 25059654]
[20]
Zhan, Y.; Zhang, H.; Liu, R.; Wang, W.; Qi, J.; Zhang, Y. Eupolyphaga sinensis Walker ethanol extract suppresses cell growth and invasion in human breast cancer cells. Integr. Cancer Ther., 2016, 15(1), 102-112.
[http://dx.doi.org/10.1177/1534735415598224] [PMID: 26242891]
[21]
Aida, M. Artonins, J. K, and L three new isoprenylated flavones from the root bark of Artocarpus heterophyllus Lamk. Heterocycles, 1993, 36, 575-580.
[http://dx.doi.org/10.3987/COM-92-6229]
[22]
Chahar, M.K.; Sharma, N.; Dobhal, M.P.; Joshi, Y.C. Flavonoids: A versatile source of anticancer drugs. Pharmacogn. Rev., 2011, 5(9), 1-12.
[http://dx.doi.org/10.4103/0973-7847.79093] [PMID: 22096313]
[23]
Batra, P.; Sharma, A.K. Anti-cancer potential of flavonoids: Recent trends and future perspectives. 3 Biotech, 2013, 3, 439-459.
[24]
Barrera, G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol., 2012, 2012137289
[http://dx.doi.org/10.5402/2012/137289] [PMID: 23119185]
[25]
Chikkula, K.V.; Raja, S. Isoxazole–a potent pharmacophore. Int. J. Pharm. Pharm. Sci., 2017, 9, 13-24.
[http://dx.doi.org/10.22159/ijpps.2017.v9i7.19097]
[26]
Inan Genç, A.; Gok, S.; Banerjee, S.; Severcan, F. Valdecoxib recovers the lipid composition, order and dynamics in colon cancer cell lines independent of COX-2 expression: An ATR-FTIR spectroscopy study. Appl. Spectrosc., 2017, 71(1), 105-117.
[http://dx.doi.org/10.1177/0003702816654164] [PMID: 27354402]
[27]
Atukorala, I.; Hunter, D.J. Valdecoxib: The rise and fall of a COX-2 inhibitor. Expert Opin. Pharmacother., 2013, 14(8), 1077-1086.
[http://dx.doi.org/10.1517/14656566.2013.783568] [PMID: 23517091]
[28]
Kivitz, A.; Eisen, G.; Zhao, W.W.; Bevirt, T.; Recker, D.P. Randomized placebo-controlled trial comparing efficacy and safety of valdecoxib with naproxen in patients with osteoarthritis. J. Fam. Pract., 2002, 51(6), 530-537.
[PMID: 12100776]
[29]
Daniels, S.E.; Torri, S.; Desjardins, P.J. Valdecoxib for treatment of primary dysmenorrhea. A randomized, double-blind comparison with placebo and naproxen. J. Gen. Intern. Med., 2005, 20(1), 62-67.
[http://dx.doi.org/10.1111/j.1525-1497.2004.30052.x] [PMID: 15693930]
[30]
Wang, D.; Dubois, R.N. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene, 2010, 29(6), 781-788.
[http://dx.doi.org/10.1038/onc.2009.421] [PMID: 19946329]
[31]
Ghorab, M.M.; El-Gaby, M.S.A.; Alsaid, M.S.; Elshaier, Y.A.M.M.; Soliman, A.M.; El-Senduny, F.F.; Badria, F.A.; Sherif, A.Y.A. Novel thiourea derivatives bearing sulfonamide moiety as anticancer agents through COX-2 inhibition. Anticancer. Agents Med. Chem., 2017, 17(10), 1411-1425.
[http://dx.doi.org/10.2174/1871520617666170327153735] [PMID: 28356021]
[32]
Hassan, A.Y.; Sarg, M.T.; Bayoumi, A.H.; Kalaf, F.G.A. Design, synthesis, and anticancer activity of novel fused purine analogues. J. Heterocycl. Chem., 2017, 54, 3458-3470.
[http://dx.doi.org/10.1002/jhet.2969]
[33]
Parker, W.B. Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem. Rev., 2009, 109(7), 2880-2893.
[http://dx.doi.org/10.1021/cr900028p] [PMID: 19476376]
[34]
Manavalan, B.; Basith, S.; Shin, T.H.; Choi, S.; Kim, M.O.; Lee, G. MLACP: Machine-learning-based prediction of anticancer peptides. Oncotarget, 2017, 8(44), 77121-77136.
[http://dx.doi.org/10.18632/oncotarget.20365] [PMID: 29100375]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy