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The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Research Article

p53-Mediated Anticancer Activity of Citrullus colocynthis Extracts

Author(s): Gaurav Joshi, Jatinder Kaur, Praveen Sharma, Gurpreet Kaur, Yuvraj Bhandari, Raj Kumar and Sandeep Singh*

Volume 9, Issue 4, 2019

Page: [303 - 311] Pages: 9

DOI: 10.2174/2210315509666181203114329

Price: $65

Abstract

Background: Current anticancer therapeutics comes with significant side effects and thus focus is shifting towards minimizing the side effects or to avoid the disease altogether. Thus, various natural products are being investigated for their potential therapeutic values which can be easily included in daily diet of a person. Citrullus colocynthis (L.) fruit is commonly used in traditional medicines and is known to have antioxidant effects, thus may possess potent anticancer activity as well.

Objectives: To establish the anticancer potential of fruit belonging to Citrullus colocynthis (L.) and delineate the potential targets.

Results: In the present study it was found that seed and pulp extracts of the fruit are effective against various cancer cell lines while the normal cells, with lower rate of division, remain largely unaffected. The current study for the first time shows that these extracts function via regulation of p53 pathways and the mode of apoptosis is mostly via mitochondrial (intrinsic) pathway. The biological profiling of the extracts was also validated using molecular modelling studies utilizing the two major polyphenols constituents from colocynths i.e., Isoorientin and Isovitexin.

Conclusion: The study suggested that the constituent has a multiple target approach for the inhibition of cancer cell proliferation and inhibition of ROS production via the major apoptotic proteins. All of these outcomes suggest and establish a critical role of ROS accumulation and mitochondrial function in the p53-dependent cell.

Keywords: Citrullus colocynthis, natural products, anticancer, free radicals, p53, molecular modeling.

Graphical Abstract
[1]
Harris, M.; Frey, P.; Esteva, M.; Gašparović-Babić, S.; Marzo-Castillejo, M.; Petek, D.; Petek Ster, M.; Thulesius, H. How health system factors influence referral decisions in patients that may have cancer: European symposium report. J. Cancer Res. Ther., 2016, 4(1), 7-10.
[http://dx.doi.org/10.14312/2052-4994.2016-2]
[2]
Selivanova, G. p53: Fighting cancer. Curr. Cancer Drug Targets, 2004, 4(5), 385-402.
[http://dx.doi.org/10.2174/1568009043332934] [PMID: 15320716]
[3]
Kumar, R.; Banerjee, U.C.; Amrutkar, S.M.; Baviskar, A.T.; Singh, S.; Joshi, G.; Kler, H. Synthesis and biological evaluation of new 2, 5-dimethylthiophene/furan based N-acetyl pyrazolines as selective topoisomerase II inhibitors. RSC Adv, 2016, 6(18), 14880-14892.
[4]
Halliwell, B.; Gutteridge, J.M. Free Radicals in Biology and Medicine; Oxford University Press: USA, 1999.
[5]
Freeman, B.A.; Crapo, J.D. Biology of disease: Free radicals and tissue injury. Lab. Invest., 1982, 47(5), 412-426.
[PMID: 6290784]
[6]
Block, G. The data support a role for antioxidants in reducing cancer risk. Nutr. Rev., 1992, 50(7), 207-213.
[http://dx.doi.org/10.1111/j.1753-4887.1992.tb01329.x] [PMID: 1641203]
[7]
Knight, J.A. Diseases related to oxygen-derived free radicals. Ann. Clin. Lab. Sci., 1995, 25(2), 111-121.
[PMID: 7785961]
[8]
Koleva, I.I.; Van Beek, T.A.; Linssen, J.P.; De Groot, A.; Evstatieva, L.N. Screening of plant extracts for antioxidant activity: A comparative study on three testing methods. Phytochem. Anal., 2002, 13(1), 8-17.
[http://dx.doi.org/10.1002/pca.611] [PMID: 11899609]
[9]
Joshi, G.; Singh, P.K.; Negi, A.; Rana, A.; Singh, S.; Kumar, R. Growth factors mediated cell signalling in prostate cancer progression: Implications in discovery of anti-prostate cancer agents. Chem. Biol. Interact., 2015, 240, 120-133.
[http://dx.doi.org/10.1016/j.cbi.2015.08.009] [PMID: 26297992]
[10]
Gordaliza, M. Natural products as leads to anticancer drugs. Clin. Transl. Oncol., 2007, 9(12), 767-776.
[http://dx.doi.org/10.1007/s12094-007-0138-9] [PMID: 18158980]
[11]
Abdel-Hassan, I.A.; Abdel-Barry, J.A.; Tariq, M.S. The hypoglycaemic and antihyperglycaemic effect of Citrullus colocynthis fruit aqueous extract in normal and alloxan diabetic rabbits. J. Ethnopharmacol., 2000, 71(1-2), 325-330.
[http://dx.doi.org/10.1016/S0378-8741(99)00215-9] [PMID: 10904181]
[12]
Kumar, S.; Kumar, D.; Manjusha, J.; Saroha, K.; Singh, N.; Vashishta, B. Antioxidant and free radical scavenging potential of Citrullus colocynthis (L.) Schrad. methanolic fruit extract. Acta Pharm., 2008, 58(2), 215-220.
[http://dx.doi.org/10.2478/v10007-008-0008-1] [PMID: 18515231]
[13]
Rajangam, J.; Christina, A. Citrullus colocynthis attenuates hyperlipidemia and hyperglycemia through its anti-oxidant property against hyperlipidemic and diabetic animal models. Pelagia Res. Library, 2013, 4(1), 60-66.
[14]
Sun, C.; Zhang, M.; Shan, X.; Zhou, X.; Yang, J.; Wang, Y.; Li-Ling, J.; Deng, Y. Inhibitory effect of cucurbitacin E on pancreatic cancer cells growth via STAT3 signaling. J. Cancer Res. Clin. Oncol., 2010, 136(4), 603-610.
[http://dx.doi.org/10.1007/s00432-009-0698-x] [PMID: 19816711]
[15]
Yasuda, S.; Yogosawa, S.; Izutani, Y.; Nakamura, Y.; Watanabe, H.; Sakai, T. Cucurbitacin B induces G2 arrest and apoptosis via a reactive oxygen species-dependent mechanism in human colon adenocarcinoma SW480 cells. Mol. Nutr. Food Res., 2010, 54(4), 559-565.
[http://dx.doi.org/10.1002/mnfr.200900165] [PMID: 19937855]
[16]
Harvey, L.A. Plant natural products in anti-diabetic drug discovery. Curr. Org. Chem., 2010, 14(16), 1670-1677.
[http://dx.doi.org/10.2174/138527210792927681]
[17]
Bhardwaj, R.; Dutta, S.; Sharma, K. Conserving biodiversity of medicinal plants from central Aravallis of Rajasthan, India. J. Environ. Res. Dev., 2011, 6(1), 69-75.
[18]
Newman, D.J.; Cragg, G.M.; Snader, K.M. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod., 2003, 66(7), 1022-1037.
[http://dx.doi.org/10.1021/np030096l] [PMID: 12880330]
[19]
Singh, D.; Singh, P.; Gupta, A.; Solanki, S.; Sharma, E.; Nema, R. Qualitative estimation of the presence of bioactive compound in Centella asiatica: An important medicinal plant. Int. J. Nanotechnol. Eng. Med., 2012, 2(1), 5-7.
[20]
Bachaya, H.A.; Iqbal, Z.; Khan, M.N.; Jabbar, A.; Gilani, A.H.; Din, I.U. In vitro and in vivo anthelmintic activity of Terminalia arjuna bark. Int. J. Agric. Biol., 2009, 11, 273.
[21]
Edeoga, H.; Okwu, D.; Mbaebie, B. Phytochemical constituents of some Nigerian medicinal plants. Afr. J. Biotechnol., 2005, 4(7), 685-688.
[http://dx.doi.org/10.5897/AJB2005.000-3127]
[22]
Kruger, N.J. In: The Protein Protocols Handbook; Springer, 2009, pp. 17-24.
[http://dx.doi.org/10.1007/978-1-59745-198-7_4]
[23]
Sharma, P.; Ghimeray, A.K.; Gurung, A.; Jin, C.W.; Rho, H.S.; Cho, D.H. Phenolic contents, antioxidant and α-glucosidase inhibition properties of Nepalese strain buckwheat vegetables. Afr. J. Biotechnol., 2013, 11(1), 184-190.
[24]
Odunfa, S.A. Carbohydrate changes in fermenting locust bean (Parkia filicoidea) duringiru preparation. Plant Foods Hum. Nutr., 1983, 32(1), 3-10.
[http://dx.doi.org/10.1007/BF01093924]
[25]
Rose, R.; Rose, C.L.; Omi, S.K.; Forry, K.R.; Durall, D.M.; Bigg, W.L. Starch determination by perchloric acid vs. enzymes: Evaluating the accuracy and precision of six colorimetric methods. J. Agric. Food Chem., 1991, 39(1), 2-11.
[http://dx.doi.org/10.1021/jf00001a001]
[26]
Negi, A.; Alex, J.M.; Amrutkar, S.M.; Baviskar, A.T.; Joshi, G.; Singh, S.; Banerjee, U.C.; Kumar, R. Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole: Microwave-assisted synthesis and anticancer activity via selective topoisomerase-II-α inhibition. Bioorg. Med. Chem., 2015, 23(17), 5654-5661.
[http://dx.doi.org/10.1016/j.bmc.2015.07.020] [PMID: 26216018]
[27]
Marklund, S.L. Extracellular superoxide dismutase and other superoxide dismutase isoenzymes in tissues from nine mammalian species. Biochem. J., 1984, 222(3), 649-655.
[http://dx.doi.org/10.1042/bj2220649] [PMID: 6487268]
[28]
Chance, B.; Maehly, A. Assay of catalases and peroxidases. Scientific Res., 1955, 2, 764-775.
[29]
Sedlak, J.; Lindsay, R.H. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem., 1968, 25(1), 192-205.
[http://dx.doi.org/10.1016/0003-2697(68)90092-4] [PMID: 4973948]
[30]
Wong, A.; Cortopassi, G.A. High-throughput measurement of mitochondrial membrane potential in a neural cell line using a fluorescence plate reader. Biochem. Biophys. Res. Commun., 2002, 298(5), 750-754.
[http://dx.doi.org/10.1016/S0006-291X(02)02546-9] [PMID: 12419317]
[31]
Baviskar, A.T.; Banerjee, U.C.; Gupta, M.; Singh, R.; Kumar, S.; Gupta, M.K.; Kumar, S.; Raut, S.K.; Khullar, M.; Singh, S.; Kumar, R. Synthesis of imine-pyrazolopyrimidinones and their mechanistic interventions on anticancer activity. Bioorg. Med. Chem., 2013, 21(18), 5782-5793.
[http://dx.doi.org/10.1016/j.bmc.2013.07.016] [PMID: 23920485]
[32]
Gurudeeban, S.; Satyavani, K.; Ramanathan, T. Bitter apple (Citrullus colocynthis): An overview of chemical composition and biomedical potentials. Asian J. Plant Sci., 2010, 9(7), 394.
[http://dx.doi.org/10.3923/ajps.2010.394.401]
[33]
Cai, Y.; Luo, Q.; Sun, M.; Corke, H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci., 2004, 74(17), 2157-2184.
[http://dx.doi.org/10.1016/j.lfs.2003.09.047] [PMID: 14969719]
[34]
Gomes, C.A.; Da Cruz, T.G.; Andrade, J.L.; Milhazes, N.; Borges, F.; Marques, M.P.M. Anticancer activity of phenolic acids of natural or synthetic origin: A structure-activity study. J. Med. Chem., 2003, 46(25), 5395-5401.
[http://dx.doi.org/10.1021/jm030956v] [PMID: 14640548]
[35]
Kim, G.J.; Chandrasekaran, K.; Morgan, W.F. Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: A review. Mutagenesis, 2006, 21(6), 361-367.
[http://dx.doi.org/10.1093/mutage/gel048] [PMID: 17065161]

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