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Current Traditional Medicine

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ISSN (Print): 2215-0838
ISSN (Online): 2215-0846

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Research Article

Antiproliferative Effects of Ocimum basilicum Methanolic Extract and Fractions, Oleanolic Acid and 3-epi-Ursolic Acid

Author(s): Kehkashan Arshad Qamar*, Ahsana Dar Farooq, Bina S. Siddiqui, Nurul Kabir and Sabira Begum

Volume 6, Issue 2, 2020

Page: [134 - 146] Pages: 13

DOI: 10.2174/2215083805666191010152439

Price: $65

Abstract

Aims: The aim of the current study was to identify active compound(s) responsible for the antiproliferative effects of O. basilicum and explore their underlying mechanism/s.

Background: Plants have been the source of medicines for the treatment of various diseases since ancient times. Ocimum basilicum (Sweet Basil, Bobai Tulsi) has been used in the folk medicine for the treatment of human liver, spleen and stomach cancers.

Objective: To emphasize the importance of O. basilicum as a potential novel non-toxic alternative to the conventional anticancer therapy.

Methods: O. basilicum (aerial parts) methanolic extract and fractions were screened against HT-144, MCF-7, NCI-H460 and SF-268 human cancer cell lines using sulforhodamine B assay. The more active Petroleum Ether Insoluble (PEI) fraction was fractionated into six sub-fractions (OB-1 to OB-6). Four pure compounds (3-O-methyl ursolic acid, oleanolic acid, 3-epi-ursolic acid and ursolic acid) were isolated from the more potent sub-fraction OB- 6. Triple channel immunofluorescence microscopy was employed to observe the effects of methanolic extract, PEI fraction, sub-fractions OB-5 and OB-6, 3-epi-ursolic acid and oleanolic acid on the cytoskeleton and nuclei of MCF-7 cells.

Results: The methanolic extract and the PEI fraction exhibited selectively greater growth inhibition against MCF-7 cell line (TGI: 56 and 36.2 µg/ml, respectively). By using triple channel immunofluorescence microscopy, it was observed that the methanolic extract, PEI fraction, sub-fraction OB-5 and 3-epi-ursolic acid induced irregular mitotic spindle formation and slowing of mitotic progression in MCF-7 cells while sub-fraction OB-6 induced mitotic arrest in the prophase stage. F-actin aggregation was also visible in PEI fraction, subfraction OB-5 and 3-epi-ursolic acid treated MCF-7 cells.

Conclusion: These results emphasize the importance of O. basilicum as a potential novel non-toxic alternative to the conventional anticancer therapy and suggest that it inhibits the growth of MCF-7 cancer cells via multiple mechanisms such as interaction with the microtubules and mitotic spindle apparatus, and F-actin aggregation.

Keywords: Ocimum basilicum, antiproliferative, 3-epi-ursolic acid, oleanolic acid, cytoskeleton, MCF-7 cell line, immunofluorescence.

Graphical Abstract

[1]
Simon JE, Morales MR, Phippen WB, Vieira RF, Hao Z. Basil: A Source of Aroma Compounds and a Popular Culinary and Ornamental Herb Perspectives on New Crops and New Uses: Biodiversity and Agricultural Sustainability. Alexandria, VA: ASHS Press 1999; pp. 499-505.
[2]
Paton A, Harley RM, Harley MM. Ocimum- An overview of relationships and classification Ocimum medicinal and aromatic plants-industrial profiles. Amsterdam: Harwood Academic 1999; pp. 1-38.
[3]
Duke JA. Handbook of Medicinal Herbs. 2nd ed. CRC Press 2002.
[http://dx.doi.org/10.1201/9781420040463]
[4]
Chalchat JC, Özcan MM. Comparative essential oil composition of flowers, leavesand stems of basil (Ocimum basilicum L.) used as herb. Food Chem 2008; 110(2): 501-3.
[http://dx.doi.org/10.1016/j.foodchem.2008.02.018] [PMID: 26049245]
[5]
Rezzoug M, Bakchiche B, Gherib A, et al. Chemical composition and bioactivity of essential oils and Ethanolic extracts of Ocimum basilicum L. and Thymus algeriensis Boiss. & Reut. from the Algerian Saharan Atlas. BMC Complement Altern Med 2019; 19(1): 146.
[http://dx.doi.org/10.1186/s12906-019-2556-y] [PMID: 31227024]
[6]
Dasgupta T, Rao AR, Yadava PK. Chemomodulatory efficacy of basil leaf (Ocimum basilicum) on drug metabolizing and antioxidant enzymes, and on carcinogen-induced skin and forestomach papillomagenesis. Phytomedicine 2004; 11(2-3): 139-51.
[http://dx.doi.org/10.1078/0944-7113-00289] [PMID: 15070164]
[7]
Sestili P, Ismail T, Calcabrini C, et al. The potential effects of Ocimum basilicum on health: A review of pharmacological and toxicological studies. Expert Opin Drug Metab Toxicol 2018; 14(7): 679-92.
[http://dx.doi.org/10.1080/17425255.2018.1484450] [PMID: 29865879]
[8]
Firenzuoli F, Gori L. Herbal medicine today: Clinical and research issues. Evid Based Complement Alternat Med 2007; 4(Suppl. 1): 37-40.
[http://dx.doi.org/10.1093/ecam/nem096] [PMID: 18227931]
[9]
Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 2003; 66(7): 1022-37.
[http://dx.doi.org/10.1021/np030096l] [PMID: 12880330]
[10]
Qamar KA, Dar A, Siddiqui BS, et al. Anticancer activity of Ocimum basilicum and the effect of ursolic acid on the cytoskeleton of MCF-7 human breast cancer cells. Lett Drug Des Discov 2010; 7: 726-36.
[http://dx.doi.org/10.2174/1570180811007010726]
[11]
Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990; 82(13): 1107-12.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[12]
Monks A, Scudiero D, Skehan P, et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst 1991; 83(11): 757-66.
[http://dx.doi.org/10.1093/jnci/83.11.757] [PMID: 2041050]
[13]
Forscher P, Smith SJ. Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J Cell Biol 1988; 107(4): 1505-16.
[http://dx.doi.org/10.1083/jcb.107.4.1505] [PMID: 3170637]
[14]
Kabir N, Schaefer AW, Nakhost A, Sossin WS, Forscher P. Protein kinase C activation promotes microtubule advance in neuronal growth cones by increasing average microtubule growth lifetimes. J Cell Biol 2001; 152(5): 1033-44.
[http://dx.doi.org/10.1083/jcb.152.5.1033] [PMID: 11238458]
[15]
Schaefer AW, Kabir N, Forscher P. Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones. J Cell Biol 2002; 158(1): 139-52.
[http://dx.doi.org/10.1083/jcb.200203038] [PMID: 12105186]
[16]
Cha H, Dangi S, Machamer CE, Shapiro P. Inhibition of mixed-lineage kinase (MLK) activity during G2-phase disrupts microtubule formation and mitotic progression in HeLa cells. Cell Signal 2006; 18(1): 93-104.
[http://dx.doi.org/10.1016/j.cellsig.2005.03.028] [PMID: 15923109]
[17]
Wang J, Wang L, Lou GH, et al. Coptidis Rhizoma: A comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Pharm Biol 2019; 57(1): 193-225.
[http://dx.doi.org/10.1080/13880209.2019.1577466] [PMID: 30963783]
[18]
Tang J, Feng Y, Tsao S, Wang N, Curtain R, Wang Y. Berberine and Coptidis rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations. J Ethnopharmacol 2009; 126(1): 5-17.
[http://dx.doi.org/10.1016/j.jep.2009.08.009] [PMID: 19686830]
[19]
Feng B, Zhu Y, Sun C, et al. Basil polysaccharide inhibits hypoxia-induced hepatocellular carcinoma metastasis and progression through suppression of HIF-1α-mediated epithelial-mesenchymal transition. Int J Biol Macromol 2019; 137(1): 32-44.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.06.189] [PMID: 31252022]
[20]
Chatterji BP, Banerjee M, Singh P, Panda D. HMBA depolymerizes microtubules, activates mitotic checkpoints and induces mitotic block in MCF-7 cells by binding at the colchicine site in tubulin. Biochem Pharmacol 2010; 80(1): 50-61.
[http://dx.doi.org/10.1016/j.bcp.2010.03.016] [PMID: 20302847]
[21]
Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anticancer Agents 2002; 2(1): 1-17.
[http://dx.doi.org/10.2174/1568011023354290] [PMID: 12678749]
[22]
Mukhtar E, Adhami VM, Mukhtar H. Targeting microtubules by natural agents for cancer therapy. Mol Cancer Ther 2014; 13(2): 275-84.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0791] [PMID: 24435445]
[23]
Akinrinmade OA, Jordaan S, Hristodorov D, et al. Human MAP Tau Based Targeted Cytolytic Fusion Proteins. Biomedicines 2017; 5(3): 36.
[http://dx.doi.org/10.3390/biomedicines5030036] [PMID: 28653985]
[24]
Penna LS, Henriques JAP, Bonatto D. Anti-mitotic agents: Are they emerging molecules for cancer treatment? Pharmacol Ther 2017; 173(1): 67-82.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.007] [PMID: 28174095]
[25]
Foerster F, Braig S, Moser C, et al. Targeting the actin cytoskeleton: Selective antitumor action via trapping PKCɛ. Cell Death Dis 2014; 5(8) 5e1398
[http://dx.doi.org/10.1038/cddis.2014.363] [PMID: 25165884]
[26]
Usui T, Kazami S, Dohmae N, et al. Amphidinolide H, a potent cytotoxic macrolide, covalently binds on actin subdomain 4 and stabilizes actin filament. Chem Biol 2004; 11(9): 1269-77.
[http://dx.doi.org/10.1016/j.chembiol.2004.07.014] [PMID: 15380187]
[27]
Stehn JR, Haass NK, Bonello T, et al. A novel class of anticancer compounds targets the actin cytoskeleton in tumor cells. Cancer Res 2013; 73(16): 5169-82.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-4501] [PMID: 23946473]
[28]
Naidu JR, Gunjan M, Chen Y, Sasidharan S. Evaluation of in vitro cytotoxic activity of Ocimum basilicum and Mentha spicata extracts. Asian J Pharm Clin Res 2016; 9(3): 131-4.
[29]
Wang X, Liu R, Zhang W, et al. Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects. Mol Cell Endocrinol 2013; 376(1-2): 70-80.
[http://dx.doi.org/10.1016/j.mce.2013.06.014] [PMID: 23791844]
[30]
Ayeleso TB, Matumba MG, Mukwevho E. Oleanolic Acid and Its Derivatives: Biological activities and therapeutic potential in chronic diseases. Molecules 2017; 22(11): 1915.
[http://dx.doi.org/10.3390/molecules22111915] [PMID: 29137205]
[31]
Lin C, Wen X, Sun H. Oleanolic acid derivatives for pharmaceutical use: A patent review. Expert Opin Ther Pat 2016; 26(6): 643-55.
[http://dx.doi.org/10.1080/13543776.2016.1182988] [PMID: 27113324]
[32]
Zhu YY, Huang HY, Wu YL. Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. Mol Med Rep 2015; 12(4): 5012-8.
[http://dx.doi.org/10.3892/mmr.2015.4033] [PMID: 26151733]
[33]
Modem S, Dicarlo SE, Reddy TR. Fresh garlic extract induces growth arrest and morphological differentiation of MCF7 breast cancer cells. Genes Cancer 2012; 3(2): 177-86.
[http://dx.doi.org/10.1177/1947601912458581] [PMID: 23050048]
[34]
Bonaccorsi I, Altieri F, Sciamanna I, et al. Endogenous reverse transcriptase as a mediator of ursolic acid’s anti-proliferative and differentiating effects in human cancer cell lines. Cancer Lett 2008; 263(1): 130-9.
[http://dx.doi.org/10.1016/j.canlet.2007.12.026] [PMID: 18282657]

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