Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

General Research Article

Leaf Extract of Nerium oleander L. Inhibits Cell Proliferation, Migration and Arrest of Cell Cycle at G2/M Phase in HeLa Cervical Cancer Cell

Author(s): Shubhasmita Mohapatra, Anil K. Biswal, Jagnehswar Dandapat and Priya R. Debata*

Volume 21, Issue 5, 2021

Published on: 11 August, 2020

Page: [649 - 657] Pages: 9

DOI: 10.2174/1871520620666200811121400

Price: $65

Abstract

Background: Cervical cancer is one of the most common gynaecological malignant tumors reported in women. Although a number of early screening and treatment options are available, mortality due to cervical cancer remains high. Nerium oleander L. is a potential medicinal plant that possesses a wide spectrum of pharmacological and physiological activities including anticancer activities.

Objective: This study aims to evaluate the antiproliferative activity, inhibition of cell migration and cell cycle arrest by the chloroform extract of leaves of Nerium Oleander L. in HeLa cervical cancer cells. The chloroform extract of Catharanthus roseus which contains anti-cancer compounds, Vinblastin and Vincristin, was used as a positive control for this study.

Methods: The chloroform extracts of Nerium oleander L. and Catharanthus roseus were prepared using the standard protocol. The cytotoxic effects were studied by MTT assay. Cell migration was studied by in vitro scratch assay. Analysis of the cell cycle was carried out by Propidium iodide staining and Flow Cytometry. The expression level of various proteins was evaluated by immunocytochemistry.

Results: In this study, we showed that the leaf extract of Nerium oleander inhibited the growth of HeLa cervical cancer cells in culture and inhibited cell migration. Besides, it arrested the cell cycle at the G2/M phase. The Epidermal Growth Factor Receptor (EGFR) expression and phosphorylated p-Rb (Ser 780) level were significantly downregulated by leaf extract of Nerium oleander.

Conclusion: The extract of Nerium oleander L. contains potential bioactive compounds that inhibit HeLa cell proliferation, cell migration and arrest cell cycle at the G2/M phase.

Keywords: Nerium oleander, HeLa cells, MTT assay, G2/M phase arrest, cell migration, antioxidant.

Graphical Abstract

[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Kataja, V.; Syrjänen, S.; Yliskoski, M.; Hippelïnen, M.; Väyrynen, M.; Saarikoski, S.; Mäntyjärvi, R.; Jokela, V.; Salonen, J.T.; Syrjänen, K. Risk factors associated with cervical human papillomavirus infections: A case-control study. Am. J. Epidemiol., 1993, 138(9), 735-745.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a116911] [PMID: 8237988]
[3]
Berchuck, A.; Rodriguez, G.; Kamel, A.; Soper, J.T.; Clarke-Pearson, D.L.; Bast, R.C.J., Jr. Expression of epidermal growth factor receptor and HER-2/neu in normal and neoplastic cervix, vulva, and vagina. Obstet. Gynecol., 1990, 76(3 Pt 1), 381-387.
[PMID: 1974342]
[4]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[5]
Pedroza-Torres, A.; López-Urrutia, E.; García-Castillo, V.; Jacobo-Herrera, N.; Herrera, L.A.; Peralta-Zaragoza, O.; López-Camarillo, C.; De Leon, D.C.; Fernández-Retana, J.; Cerna-Cortés, J.F.; Pérez-Plasencia, C. MicroRNAs in cervical cancer: Evidences for a miRNA profile deregulated by HPV and its impact on radio-resistance. Molecules, 2014, 19(5), 6263-6281.
[http://dx.doi.org/10.3390/molecules19056263] [PMID: 24840898]
[6]
Lin, S.R.; Chang, C.H.; Hsu, C.F.; Tsai, M.J.; Cheng, H.; Leong, M.K.; Sung, P.J.; Chen, J.C.; Weng, C.F. Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. Br. J. Pharmacol., 2020, 177(6), 1409-1423.
[http://dx.doi.org/10.1111/bph.14816] [PMID: 31368509]
[7]
Gammone, M.A.; Riccioni, G.; Galvano, F.; D’Orazio, N. Novel therapeutic strategies against cancer: Marine-derived drugs may be the answer? Anticancer. Agents Med. Chem., 2016, 16(12), 1549-1557.
[http://dx.doi.org/10.2174/1871520616666160211123841] [PMID: 26863883]
[8]
Tsai, A.C.; Wang, C.Y.; Liou, J.P.; Pai, H.C.; Hsiao, C.J.; Chang, J.Y.; Wang, J.C.; Teng, C.M.; Pan, S.L. Orally active microtubule-targeting agent, MPT0B271, for the treatment of human non-small cell lung cancer, alone and in combination with erlotinib. Cell Death Dis., 2014, 5(4), e1162.
[http://dx.doi.org/10.1038/cddis.2014.128] [PMID: 24722287]
[9]
Balkrishna, A.; Das, S.K.; Pokhrel, S.; Joshi, A. Laxmi; Verma, S.; Sharma, V.K.; Sharma, V.; Sharma, N.; Joshi, C.S. Colchicine: Isolation, LC–MS QTof screening, and anticancer activity study of Gloriosa superba seeds. Molecules, 2019, 24(15), 2772.
[http://dx.doi.org/10.3390/molecules24152772]
[10]
Singh, R.; Ferrin, D.M.; Huang, Q. First report of Xylella fastidiosa associated with Oleander leaf scorch in Louisiana. Plant Dis., 2010, 94(2), 274.
[http://dx.doi.org/10.1094/PDIS-94-2-0274B] [PMID: 30754273]
[11]
Rashan, L.J.; Franke, K.; Khine, M.M.; Kelter, G.; Fiebig, H.H.; Neumann, J.; Wessjohann, L.A. Characterization of the anticancer properties of monoglycosidic cardenolides isolated from Nerium oleander and Streptocaulon tomentosum. J. Ethnopharmacol., 2011, 134(3), 781-788.
[http://dx.doi.org/10.1016/j.jep.2011.01.038] [PMID: 21291990]
[12]
Cao, Y.L.; Zhang, M.H.; Lu, Y.F.; Li, C.Y.; Tang, J.S.; Jiang, M.M. Cardenolides from the leaves of Nerium oleander. Fitoterapia, 2018, 127, 293-300.
[http://dx.doi.org/10.1016/j.fitote.2018.03.004] [PMID: 29540313]
[13]
Bai, L.; Wang, L.; Zhao, M.; Toki, A.; Hasegawa, T.; Ogura, H.; Kataoka, T.; Hirose, K.; Sakai, J.; Bai, J.; Ando, M. Bioactive pregnanes from Nerium oleander. J. Nat. Prod., 2007, 70(1), 14-18.
[http://dx.doi.org/10.1021/np068030o] [PMID: 17253842]
[14]
Calderón-Montaño, J.M.; Burgos-Morón, E.; Orta, M.L.; Mateos, S.; López-Lázaro, M. A hydroalcoholic extract from the leaves of Nerium oleander inhibits glycolysis and induces selective killing of lung cancer cells. Planta Med., 2013, 79(12), 1017-1023.
[http://dx.doi.org/10.1055/s-0032-1328715] [PMID: 23824549]
[15]
Pathak, S.; Multani, A.S.; Narayan, S.; Kumar, V.; Newman, R.A. Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells. Anticancer Drugs, 2000, 11(6), 455-463.
[http://dx.doi.org/10.1097/00001813-200007000-00006] [PMID: 11001386]
[16]
Zhao, M.; Zhang, S.; Fu, L.; Li, N.; Bai, J.; Sakai, J.; Wang, L.; Tang, W.; Hasegawa, T.; Ogura, H.; Kataoka, T.; Oka, S.; Kiuch, M.; Hirose, K.; Ando, M. Taraxasterane- and ursane-type triterpenes from Nerium oleander and their biological activities. J. Nat. Prod., 2006, 69(8), 1164-1167.
[http://dx.doi.org/10.1021/np0680073] [PMID: 16933868]
[17]
Müller, B.M.; Rosskopf, F.; Paper, D.H.; Kraus, J.; Franz, G. Polysaccharides from Nerium oleander: Structure and biological activity. Pharmazie, 1991, 46(9), 657-663.
[PMID: 1798730]
[18]
Ko, Y.S.; Rugira, T.; Jin, H.; Park, S.W.; Kim, H.J. Oleandrin and its derivative Odoroside A, both cardiac glycosides, exhibit anticancer effects by inhibiting invasion via suppressing the STAT-3 signaling pathway. Int. J. Mol. Sci., 2018, 19(11), 3350.
[http://dx.doi.org/10.3390/ijms19113350] [PMID: 30373171]
[19]
Dunn, D.E.; He, D.N.; Yang, P.; Johansen, M.; Newman, R.A.; Lo, D.C. in vitro and in vivo neuroprotective activity of the cardiac glycoside oleandrin from Nerium oleander in brain slice-based stroke models. J. Neurochem., 2011, 119(4), 805-814.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07439.x] [PMID: 21950737]
[20]
Wen, S.Y.; Chen, Y.Y.; Deng, C.M.; Zhang, C.Q.; Jiang, M.M. Nerigoside suppresses colorectal cancer cell growth and metastatic potential through inhibition of ERK/GSK3β/β-catenin signaling pathway. Phytomedicine, 2019, 57, 352-363.
[http://dx.doi.org/10.1016/j.phymed.2018.12.033] [PMID: 30831484]
[21]
Kars, M.D.; Gündüz, U.; Üney, K.; Baş, A.L. Exploring a natural MDR reversal agent: Potential of medicinal food supplement Nerium oleander leaf distillate. Asian Pac. J. Trop. Biomed., 2013, 3(8), 644-649.
[http://dx.doi.org/10.1016/S2221-1691(13)60130-6] [PMID: 23905023]
[22]
Pan, Y.; Rhea, P.; Tan, L.; Cartwright, C.; Lee, H.J.; Ravoori, M.K.; Addington, C.; Gagea, M.; Kundra, V.; Kim, S.J.; Newman, R.A.; Yang, P. PBI-05204, a supercritical CO2 extract of Nerium oleander, inhibits growth of human pancreatic cancer via targeting the PI3K/mTOR pathway. Invest. New Drugs, 2015, 33(2), 271-279.
[http://dx.doi.org/10.1007/s10637-014-0190-6] [PMID: 25476893]
[23]
Ainsworth, E.A.; Gillespie, K.M. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent. Nat. Protoc., 2007, 2(4), 875-877.
[http://dx.doi.org/10.1038/nprot.2007.102] [PMID: 17446889]
[24]
Sai, K.; Thapa, R.; Devkota, H.P.; Joshi, K.R. Phytochemical screening, free radical scavenging and α-amylase inhibitory activities of selected medicinal plants from Western Nepal. Medicines (Basel), 2019, 6(2), 70.
[http://dx.doi.org/10.3390/medicines6020070] [PMID: 31242563]
[25]
Choi, H.Y.; Jhun, E.J.; Lim, B.O.; Chung, I.M.; Kyung, S.H.; Park, D.K. Application of flow injection--chemiluminescence to the study of radical scavenging activity in plants. Phytother. Res., 2000, 14(4), 250-253.
[http://dx.doi.org/10.1002/1099-1573(200006)14:4<250::AID-PTR587>3.0.CO;2-J] [PMID: 10861967]
[26]
Vichai, V.; Kirtikara, K.; Sulforhodamine, B. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc., 2006, 1(3), 1112-1116.
[http://dx.doi.org/10.1038/nprot.2006.179] [PMID: 17406391]
[27]
Gebäck, T.; Schulz, M.M.P.; Koumoutsakos, P.; Detmar, M. TScratch: A novel and simple software tool for automated analysis of monolayer wound healing assays. Biotechniques, 2009, 46(4), 265-274.
[http://dx.doi.org/10.2144/000113083] [PMID: 19450233]
[28]
Grada, A.; Otero-Vinas, M.; Prieto-Castrillo, F.; Obagi, Z.; Falanga, V. Research techniques made simple: Analysis of collective cell migration using the wound healing assay. J. Invest. Dermatol., 2017, 137(2), e11-e16.
[http://dx.doi.org/10.1016/j.jid.2016.11.020] [PMID: 28110712]
[29]
Tuan Anh, H.L.; Tran, P.T.; Thao, D.T.; Trang, D.T.; Dang, N.H.; Van Cuong, P.; Kiem, P.V.; Minh, C.V.; Lee, J.H. Degalactotigonin, a steroidal glycoside from Solanum nigrum, induces apoptosis and cell cycle arrest via inhibiting the EGFR signaling pathways in pancreatic cancer cells. BioMed Res. Int., 2018, 2018, 3120972.
[http://dx.doi.org/10.1155/2018/3120972] [PMID: 30643798]
[30]
Jafari, S.; Saeidnia, S.; Abdollahi, M. Role of natural phenolic compounds in cancer chemoprevention via regulation of the cell cycle. Curr. Pharm. Biotechnol., 2014, 15(4), 409-421.
[http://dx.doi.org/10.2174/1389201015666140813124832] [PMID: 25312621]
[31]
Ngabire, D.; Seong, Y.A.; Patil, M.P.; Niyonizigiye, I.; Seo, Y.B.; Kim, G.D. Induction of apoptosis and G1 phase cell cycle arrest by Aster incisus in AGS gastric adenocarcinoma cells. Int. J. Oncol., 2018, 53(5), 2300-2308.
[PMID: 30226597]
[32]
Tripathi, S.K.; Biswal, B.K. Pterospermum acerifolium (L.) wild bark extract induces anticarcinogenic effect in human cancer cells through mitochondrial-mediated ROS generation. Mol. Biol. Rep., 2018, 45(6), 2283-2294.
[http://dx.doi.org/10.1007/s11033-018-4390-6] [PMID: 30267191]
[33]
Chaudhary, S.; Chandrashekar, K.S.; Pai, K.S.R.; Setty, M.M.; Devkar, R.A.; Reddy, N.D.; Shoja, M.H. Evaluation of antioxidant and anticancer activity of extract and fractions of Nardostachys jatamansi DC in breast carcinoma. BMC Complement. Altern. Med., 2015, 15(50), 50.
[http://dx.doi.org/10.1186/s12906-015-0563-1] [PMID: 25886964]
[34]
Comín-Anduix, B.; Agell, N.; Bachs, O.; Ovádi, J.; Cascante, M. A new bis-indole, KARs, induces selective M arrest with specific spindle aberration in neuroblastoma cell line SH-SY5Y. Mol. Pharmacol., 2001, 60(6), 1235-1242.
[http://dx.doi.org/10.1124/mol.60.6.1235] [PMID: 11723230]
[35]
Chen, J.; Huang, X.; Tao, C.; Xiao, T.; Li, X.; Zeng, Q.; Ma, M.; Wu, Z. Artemether attenuates the progression of non-small cell lung cancer by inducing apoptosis, cell cycle arrest and promoting cellular senescence. Biol. Pharm. Bull., 2019, 42(10), 1720-1725.
[http://dx.doi.org/10.1248/bpb.b19-00391] [PMID: 31378747]
[36]
Seshacharyulu, P.; Ponnusamy, M.P.; Haridas, D.; Jain, M.; Ganti, A.K.; Batra, S.K. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin. Ther. Targets, 2012, 16(1), 15-31.
[http://dx.doi.org/10.1517/14728222.2011.648617] [PMID: 22239438]
[37]
Scheffner, M.; Münger, K.; Byrne, J.C.; Howley, P.M. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc. Natl. Acad. Sci. USA, 1991, 88(13), 5523-5527.
[http://dx.doi.org/10.1073/pnas.88.13.5523] [PMID: 1648218]

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