EVALUATION OF PRO-APOPTOTIC EFFECTS OF β-MONOLINOLEIN ON METASTATIC BREAST CANCER CELL LINE MDA-MB-231

MOHAMMED SHAFI SOFI

doi:10.22159/ajpcr.2019.v12i3.30130

Authors

MOHAMMED SHAFI SOFI Department of Microbiology and Biotechnology, Molecular Diagnostics and Nanobiotechnology Laboratories, Bangalore University, J.B. Campus, Bengaluru, Karnataka, India.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i3.30130

Keywords:

Nil

Abstract

Objectives: The objective of this study was to evaluate the β-monolinolein as a potential therapy for breast cancer treatment.

Methods: The cytotoxic activity of β-monolinolein was evaluated by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue exclusion assay. The cellular cytotoxicity and levels of cytosolic enzyme, lactate dehydrogenase (LDH), were measured by assessing μmoles of nicotinamide adenine dinucleotide/well/min. To confirm whether β-monolinolein induces apoptosis in 3,4-methylenedioxyamphetamine (MDA)- MB-231 cells, western blot and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis were performed.

Results: For the 1st time, it was demonstrated that β-monolinolein strongly inhibits the growth of MDA-MB-231 cells, with an half maximal inhibitory concentration value of 12.5 μg/ml. <90% of cell death was achieved at higher concentrations after 48 h of treatment. Trypan blue assay showed that the cell viability was significantly decreased in a dose-dependent manner in MDA-MB-231 cells after 48 h of treatment. On the other hand, LDH activities in the cultured media were significantly elevated in a dose-dependent manner as compared to the control. Further, the western blot analysis showed that β-monolinolein leads to change in expression levels of important cell cycle regulators such as p21, Bax, Bcl-Xl, and Bcl-2 in MDA-MB-231 cells. The semiquantitative RT-PCR results indicated a significant upregulation of proapoptotic genes such as p53, p21, and Bax and downregulation of antiapoptotic gene Bcl-2.

Conclusion: These results indicate that β-monolinolein leads to change in expression of various cell cycle/apoptotic regulators and hence induces death in MDA-MB-231 cells.

Downloads

Download data is not yet available.

References

Song X, Xiong Y, Qi X, Tang W, Dai J, Gu Q, et al. Molecular targets of active anticancer compounds derived from marine sources. Mar Drugs 2018;16:175.

World Health Organization. World Cancer Report. Geneva, Switzerland: WHO; 2018.

Lieu CH, William WN, Lippman SM. Cancer chemoprevention. In: Hidalgo M, Eckhardt SG, Garrett-Mayer E, Clendeninn NJ, editors. Principles of Anticancer Drug Development. New York: Springer Science; 2010. p. 1-18.

Patsialou A, Wang Y, Lin J, Whitney K, Goswami S, Kenny PA, et al. Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients. Breast Cancer Res 2012;14:R139.

WHO. Cancer-Fact Sheets. WHO. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/index.html. [Last cited on 2017 Jan 02].

Ruiz-Torres V, Encinar JA, Herranz-López M, Pérez-Sánchez A, Galiano V, Barrajón-Catalán E, et al. An updated review on marine anticancer compounds: The use of virtual screening for the discovery of small-molecule cancer drugs. Molecules 2017;22:1037.

Kaliberov SA, Buchsbaum DJ. Chapter seven-cancer treatment with gene therapy and radiation therapy. Adv Cancer Res 2012;115:221-63.

Hu Y, Fu L. Targeting cancer stem cells: A new therapy to cure cancer patients. Am J Cancer Res 2012;2:340-56.

Capua CJ, Hopson NP, Stewart CM, Johnston GR, O’Neill KL, Schaalje GB, et al. Cytotoxicity of Atriplex confertifolia. J Toxicol 2010;2010:976548.

Song YH, Sun H, Zhang AH, Yan GL, Han Y, Wang XJ. Plant derived natural products as leads to anticancer drugs. J Med Plant Herb Ther Res 2014;2:6-15.

George S, Bhalerao SV, Lidstone EA, Ahmad IS, Abbasi A, Cunningham BT, et al. Cytotoxicity screening of Bangladeshi medicinal plant extracts on pancreatic cancer cells. BMC Complement Altern Med 2010;10:52.

Russo R, Corasaniti MT, Bagetta G, Morrone LA. Exploitation of cytotoxicity of some essential oils for translation in cancer therapy. Evid Based Complement Alternat Med 2015;2015:397821.

Butler MS, Newman DJ. Mother nature’s gifts to diseases of man: The impact of natural products on anti-infective, anticholestemics and anticancer drug discovery. Prog Drug Res 2008;65:1, 3-44.

Molinari G. Natural products in drug discovery: Present status and perspectives. Adv Exp Med Biol 2009;655:13-27.

Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anti-cancer agents. Chem Rev 2009;109:3012-43.

Hickman JA. Apoptosis induced by anticancer drugs. Cancer Metastasis Rev 1992;11:121-39.

Koch S, Mayer F, Honecker F, Schittenhelm M, Bokemeyer C. Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumours under normoxic and hypoxic conditions in vitro. Br J Cancer 2003;89:2133-9.

Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res 1987;47:936-42.

Alami N, Paterson J, Belanger S, Juste S, Grieshaber CK, Leyland-Jones B, et al. Comparative analysis of xanafide cytotoxicity in breast cancer cell lines. Br J Cancer 2007;97:58-64.

Andersson A, Fagerberg J, Lewensohn R, Ehrsson H. Pharmacokinetics of cisplatin and its monohydrated complex in humans. J Pharm Sci 1996;85:824-7.

Sorenson CM, Barry MA, Eastman A. Analysis of events associated with cell cycle arrest at G2 phase and cell death induced by cisplatin. J Natl Cancer Inst 1990;82:749-55.

Eastman A. Activation of programmed cell death by anticancer agents: Cisplatin as a model system. Cancer Cells 1990;2:275-80.

Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007;70:461-77.

Vadodkar AS, Suman S, Lakshmanaswamy R, Damodaran C. Chemoprevention of breast cancer by dietary compounds. Anticancer Agents Med Chem 2012;12:1185-202.

Wang H, Khor TO, Shu L, Su ZY, Fuentes F, Lee JH, et al. Plants vs. Cancer: A review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer Agents Med Chem 2012;12:1281-305.

Fabio A, Cermelli C, Fabio G, Nicoletti P, Quaglio P. Screening of the antibacterial effects of a variety of essential oils on microorganisms responsible for respiratory infections. Phytother Res 2007;21:374-7.

Villarini M, Pagiotti R, Dominici L, Fatigoni C, Vannini S, Levorato S, et al. Investigation of the cytotoxic, genotoxic, and apoptosis-inducing effects of estragole isolated from fennel (Foeniculum vulgare). J Nat Prod 2014;77:773-8.

Steward WP, Brown K. Cancer chemoprevention: A rapidly evolving field. Br J Cancer 2013;109:1-7.

Sofi MS, Sateesh MK, Bashir M, Ganie MA, Nabi S. Chemopreventive and anti-breast cancer activity of compounds isolated from leaves of Abrus precatorius L. 3 Biotech 2018;8:371.

Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N, et al. Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol 2004;90:161-6.

Rashid MH, Bharadwaj DP, Majumder S, Mandal V, Pal M, Chandra SM, et al. Antioxidant and anticancer activity of extract and fractions obtained from Diospyros melanoxylon Roxb. Leaves and correlation with their polyphenolic profiles. Int J Pharm Pharm Sci 2018;10:6-16.

Banerjee S, Wang Z, Mohammad M, Sarkar FH, Mohammad RM. Efficacy of selected natural products as therapeutic agents against cancer. J Nat Prod 2008;71:492-6.

Boik J. Natural Compounds in Cancer Therapy. USA: Oregon Medical Press; 2001.

Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res 2000;78:199-334.

Chabner BA, Roberts TG Jr. Timeline: Chemotherapy and the war on cancer. Nat Rev Cancer 2005;5:65-72.

Lall RK, Syed DN, Adhami VM, Khan MI, Mukhtar H. Dietary polyphenols in prevention and treatment of prostate cancer. Int J Mol Sci 2015;16:3350-76.

Nirmala JM, Samundeeswari A, Sankar DP. Natural plant resources in anticancer therapy-a review. Res Plant Biol 2011;1:1-14.

Cardellina JH, Fuller RW, Gamble WR, Westergaard C, Boswell J, Munro MH, et al. Evolving strategies for the selection dereplication and prioritization of antitumor and HIV inhibitory natural products extracts. In: Bioassay Methods in Natural Product Research and Development. Dordrecht, Netherlands: Kluwer Academic Publishers; 1999.

Sofi MS, Nabi S. Induction of caspase-3 dependent apoptosis, cell cycle arrest and cytotoxicity in breast cancer cells by Abrus precatorius. Int J Pharm Pharm Sci 2018;10:29-35.

Aziz AA, Rady HM, Amer MA, Kiwan HS. Effect of some honey bee extracts on the proliferation, proteolytic and gelatinolytic activities of the hepatocellular carcinoma Hep-G2 cell line. Aust J Basic Appl Sci 2009;3:2754-69.

Lee SD, Guijae YE, Chae EH, Man-Jin IE, Nam-Soon OE, Yoon KH, et al. Lipid soluble extracts as the main source of anticancer activity in ginseng and ginseng marc. J Am Oil Chem Soc 2009;86:1065-71.

Weyermann J, Lochmann D, Zimmer A. A practical note on the use of cytotoxicity assays. Int J Pharm 2005;288:369-76.

Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB. Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: Its suppression by ectopic expression of bcl-2 and bcl-xl. Carcinogenesis 2002;23:143-50.

Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003;3:768-80.

Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med 2004;10:789-99.

Yang F, Oz HS, Barve S, de Villiers WJ, McClain CJ, Varilek GW, et al. The green tea polyphenol (-)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6. Mol Pharmacol 2001;60:528-33.

Ola MS, Nawaz M, Ahsan H. Role of bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 2011;351:41-58.