Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Apoptosis of Leukemia Cells by Ocimum basilicum Fractions Following TNF alpha Induced Activation of JNK and Caspase 3

Author(s): Touseef Rehan, David MacEwan, Nasrullah Shah, Tabassum Rehan, Riffat Tahira, Sheeba Murad, Mariam Anees, Iram Murtaza, Muhammad Farman, Obaid-ur-Rahman Abid and Aneesa Sultan*

Volume 25, Issue 34, 2019

Page: [3681 - 3691] Pages: 11

DOI: 10.2174/1381612825666191011100826

Price: $65


Purpose: Leukemia, one of the major cancers, affects a large proportion of people around the world. Better treatment options for leukemia are required due to a large number of side effects associated with current therapeutic regimens. In the present study, we sought to determine the pathway of triggering apoptosis of leukemic cells by Ocimum basilicum (O. basilicum) plant extract.

Materials/Methods: Methanolic extract of the O. basilicum plant material was prepared. The crude extract was fractionated into several fractions through column chromatography using ethyl acetate and n-hexane as eluting solvents. Cell viability of leukemic cells was assessed via Cell titer GLO assay and apoptosis was measured through Annexin V/PI staining. Two apoptotic molecules JNK and caspases were analyzed through western blotting while pro-inflammatory cytokines TNFα, CCL2 and CXCL8 using qPCR. Fractions were characterized through LC-MS.

Results: The most potent with lowest IC50 values among the fractions were BF2 (2:8 n-hexane:ethyl acetate) and BF3 (3:7 n-hexane:ethyl acetate). Cytotoxicity was associated with apoptosis. Apoptosis was found caspasedependent and P-JNK activation was detected sustained. A significant increase in the level of TNF α and a decrease in the level of CXCL8 were observed in BF2 and BF3 treated cells.

Conclusion: The fractions of O. basilicum extract were found to kill cells following JNK pathway activation. Excellent results were obtained with BF2 and BF3 probably due to predominant Epicatechin and Cinnamic acid derivatives in these fractions.

Keywords: Apoptosis, cytokines, cytotoxicity, leukemia, natural products, Ocimum basilicum.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007; 57(1): 43-66.
[] [PMID: 17237035]
Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M. Swedish Acute Leukemia Registry Group. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 2012; 119(17): 3890-9.
[] [PMID: 22383796]
Tao JJ, Visvanathan K, Wolff AC. Long term side effects of adjuvant chemotherapy in patients with early breast cancer. Breast 2015; 24(Suppl. 2): S149-53.
[] [PMID: 26299406]
Soni G, Yadav KS. Applications of nanoparticles in treatment and diagnosis of leukemia. Mater Sci Eng C 2015; 47: 156-64.
[] [PMID: 25492184]
Ahmed S, Kamal T, Khan SA, et al. Assessment of anti-bacterial Ni-Al/chitosan composite spheres for adsorption assisted photo-degradation of organic pollutants. Curr Nanosci 2016; 12: 569-75.
Ali F, Khan SB, Kamal T, Alamry KA, Asiri AM. Chitosan-titanium oxide fibers supported zero-valent nanoparticles: highly efficient and easily retrievable catalyst for the removal of organic pollutants. Sci Rep 2018; 8(1): 6260.
[] [PMID: 29674721]
Ali F, Khan SB, Kamal T, et al. Synthesis and characterization of metal nanoparticles templated chitosan-SiO2 catalyst for the reduction of nitrophenols and dyes. Carbohydr Polym 2018; 192: 217-30.
[] [PMID: 29691016]
Ali F, Khan SB, Kamal T, Anwar Y, Alamry KA, Asiri AM. Anti-bacterial chitosan/zinc phthalocyanine fibers supported metallic and bimetallic nanoparticles for the removal of organic pollutants. Carbohydr Polym 2017; 173: 676-89.
[] [PMID: 28732913]
Ali F, Khan SB, Kamal T, Anwar Y, Alamry KA, Asiri AM. Bactericidal and catalytic performance of green nanocomposite based-on chitosan/carbon black fiber supported monometallic and bimetallic nanoparticles. Chemosphere 2017; 188: 588-98.
[] [PMID: 28917211]
Haider S, Kamal T, Khan SB, et al. Natural polymers supported copper nanoparticles for pollutants degradation. Appl Surf Sci 2016; 387: 1154-61.
Kamal T, Anwar Y, Khan SB, Chani MTS, Asiri AM. Dye adsorption and bactericidal properties of TiO2/chitosan coating layer. Carbohydr Polym 2016; 148: 153-60.
[] [PMID: 27185126]
Kamal T, Khan SB, Asiri AM. Synthesis of zero-valent Cu nanoparticles in the chitosan coating layer on cellulose microfibers: evaluation of azo dyes catalytic reduction. Cellulose 2016; 23: 1911-23.
Kamal T, Khan SB, Asiri AM. Nickel nanoparticles-chitosan composite coated cellulose filter paper: an efficient and easily recoverable dip-catalyst for pollutants degradation. Environ Pollut 2016; 218: 625-33.
[] [PMID: 27481647]
Kamal T, Ul-Islam M, Khan SB, Asiri AM. Adsorption and photocatalyst assisted dye removal and bactericidal performance of ZnO/chitosan coating layer. Int J Biol Macromol 2015; 81: 584-90.
[] [PMID: 26321421]
Khan SA, Khan SB, Kamal T, Asiri AM, Akhtar K. Recent development of chitosan nanocomposites for environmental applications. Recent Pat Nanotechnol 2016; 10(3): 181-8.
[] [PMID: 27136929]
Khan SA, Khan SB, Kamal T, Yasir M, Asiri AM. Antibacterial nanocomposites based on chitosan/Co-MCM as a selective and efficient adsorbent for organic dyes. Int J Biol Macromol 2016; 91: 744-51.
[] [PMID: 27287771]
Khan SB, Khan SA, Marwani HM, et al. Anti-bacterial PES-cellulose composite spheres: dual character toward extraction and catalytic reduction of nitrophenol. RSC Advances 2016; 6: 110077-90.
Ul-Islam M, Wajid Ullah M, Khan S, et al. Recent advancement in cellulose based nanocomposite for addressing environmental challenges. Recent Pat Nanotechnol 2016; 10(3): 169-80.
[] [PMID: 27136931]
Behbahani M. Evaluation of in vitro anticancer activity of Ocimum basilicum, Alhagi maurorum, Calendula officinalis and their parasite Cuscuta campestris. PLoS One 2014; 9(12)e116049
[] [PMID: 25548920]
Jaganathan SK, Mazumdar A, Mondhe D, Mandal M. Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biol Int 2011; 35(6): 607-15.
[] [PMID: 21044050]
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.
Manosroi J, Dhumtanom P, Manosroi A. Anti-proliferative activity of essential oil extracted from Thai medicinal plants on KB and P388 cell lines. Cancer Lett 2006; 235(1): 114-20.
[] [PMID: 15979235]
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.
[] [PMID: 15070164]
Rushworth SA, Zaitseva L, Murray MY, Shah NM, Bowles KM, MacEwan DJ. The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance. Blood 2012; 120(26): 5188-98.
[] [PMID: 23077289]
Cao XH, Wang AH, Wang CL, et al. Surfactin induces apoptosis in human breast cancer MCF-7 cells through a ROS/JNK-mediated mitochondrial/caspase pathway. Chem Biol Interact 2010; 183(3): 357-62.
[] [PMID: 19954742]
Pavia DL, Lampman GM, Kriz GS, Vyvyan JA. Introduction to spectroscopy. Cengage Learning Stamford 2014.
Schafer ZT, Kornbluth S. The apoptosome: physiological, developmental, and pathological modes of regulation. Dev Cell 2006; 10(5): 549-61.
[] [PMID: 16678772]
Mukhtar E, Adhami VM, Khan N, Mukhtar H. Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents. Curr Drug Targets 2012; 13(14): 1831-41.
[] [PMID: 23140293]
Bhatia D, Mandal A, Nevo E, Bishayee A. Apoptosis-inducing effects of extracts from desert plants in HepG2 human hepatocarcinoma cells. Asian Pac J Trop Biomed 2015; 5: 87-92.
Wang Q, Salman H, Danilenko M, Studzinski GP. Cooperation between antioxidants and 1,25-dihydroxyvitamin D3 in induction of leukemia HL60 cell differentiation through the JNK/AP-1/Egr-1 pathway. J Cell Physiol 2005; 204(3): 964-74.
[] [PMID: 15799027]
Zhou G-B, Zhang J, Wang Z-Y, Chen S-J, Chen Z. Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. Philos Trans R Soc Lond B Biol Sci 2007; 362(1482): 959-71.
[] [PMID: 17317642]
Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene 2008; 27(48): 6245-51.
[] [PMID: 18931691]
Kolomeichuk SN, Terrano DT, Lyle CS, Sabapathy K, Chambers TC. Distinct signaling pathways of microtubule inhibitors--vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively. FEBS J 2008; 275(8): 1889-99.
[] [PMID: 18341588]
Zhong F, Tong Z-T, Fan L-L, et al. Guggulsterone-induced apoptosis in cholangiocarcinoma cells through ROS/JNK signaling pathway. Am J Cancer Res 2016; 6(2): 226-37.
[PMID: 27186398]
Tsujimoto Y, Shimizu S. Another way to die: autophagic programmed cell death. Cell Death Differ 2005; 12(Suppl. 2): 1528-34.
[] [PMID: 16247500]
Horbinski C, Chu CT. Kinase signaling cascades in the mitochondrion: a matter of life or death. Free Radic Biol Med 2005; 38(1): 2-11.
[] [PMID: 15589366]
Looi CY, Arya A, Cheah FK, et al. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds. PLoS One 2013; 8(2)e56643
[] [PMID: 23437193]
Woo HJ, Jun Y, Lee JY, Woo MH, Yang CH, Kim YH. Apoptogenic activity of 2α,3α-dihydroxyurs-12-ene-28-oic acid from Prunella vulgaris var. lilacina is mediated via mitochondria-dependent activation of caspase cascade regulated by Bcl-2 in human acute leukemia Jurkat T cells. J Ethnopharmacol 2011; 135(3): 626-35.
[] [PMID: 21473903]
Chen T, Wong Y-S. Selenocystine induces caspase-independent apoptosis in MCF-7 human breast carcinoma cells with involvement of p53 phosphorylation and reactive oxygen species generation. Int J Biochem Cell Biol 2009; 41(3): 666-76.
[] [PMID: 18718551]
Wong FC, Woo CC, Hsu A, Tan BKH. The anti-cancer activities of Vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways. PLoS One 2013; 8(10)e78021
[] [PMID: 24205071]
Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2002; 2(6): 420-30.
[] [PMID: 12189384]
Bröker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res 2005; 11(9): 3155-62.
[] [PMID: 15867207]
Kargi A, Yalcin AD, Erin N, Savas B, Polat HH, Gorczynski RM. IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer. Clin Lab 2012; 58(5-6): 501-5.
[PMID: 22783581]
Varney ML, Singh S, Li A, Mayer-Ezell R, Bond R, Singh RK. Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. Cancer Lett 2011; 300(2): 180-8.
[] [PMID: 21035946]
Oladipo O, Conlon S, O’Grady A, et al. The expression and prognostic impact of CXC-chemokines in stage II and III colorectal cancer epithelial and stromal tissue. Br J Cancer 2011; 104(3): 480-7.
[] [PMID: 21285972]
Chen Y, Shi M, Yu G-Z, et al. Interleukin-8, a promising predictor for prognosis of pancreatic cancer. World J Gastroenterol 2012; 18(10): 1123-9.
[] [PMID: 22416189]
Dimberg J, Ström K, Löfgren S, Zar N, Lindh M, Matussek A. DNA promoter methylation status and protein expression of interleukin-8 in human colorectal adenocarcinomas. Int J Colorectal Dis 2012; 27(6): 709-14.
[] [PMID: 22108905]
Takanashi K, Suda M, Matsumoto K, et al. Epicatechin oligomers longer than trimers have anti-cancer activities, but not the catechin counterparts. Sci Rep 2017; 7(1): 7791.
[] [PMID: 28798415]
Shay J, Elbaz HA, Lee I, Zielske SP, Malek MH, Hüttemann M. Molecular mechanisms and therapeutic effects of (-)-epicatechin and other polyphenols in cancer, inflammation, diabetes, and neurodegeneration. Oxid Med Cell Longev 2015; 2015181260
Rao CV, Desai D, Kaul B, Amin S, Reddy BS. Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth. Chem Biol Interact 1992; 84(3): 277-90.
[] [PMID: 1423745]
Tyszka-Czochara M, Konieczny P, Majka M. Caffeic acid expands anti-tumor effect of metformin in human metastatic cervical carcinoma HTB-34 cells: implications of AMPK activation and impairment of fatty acids de novo biosynthesis. Int J Mol Sci 2017; 18(2): 462.
[] [PMID: 28230778]
Song X, Lorenzi PL, Landowski CP, Vig BS, Hilfinger JM, Amidon GL. Amino acid ester prodrugs of the anticancer agent gemcitabine: synthesis, bioconversion, metabolic bioevasion, and hPEPT1-mediated transport. Mol Pharm 2005; 2(2): 157-67.
[] [PMID: 15804190]
De P, Baltas M, Bedos-Belval F. Cinnamic acid derivatives as anticancer agents-a review. Curr Med Chem 2011; 18(11): 1672-703.
[] [PMID: 21434850]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy