Preliminary Cytotoxic Activity of Sutherlandia frutescens and Carpobrotus edulis on Malignant glioblastoma Cells doi.org/10.26538/tjnpr/v3i5.5

Main Article Content

Sylvester I. Omoruyi
Adaze B. Enogieru
Okobi E. Ekpo

Abstract

Glioblastoma (GBM) is the most common and aggressive intracranial tumour with limited therapeutic options due to their high tumour vasculature and invasiveness. Treatment of GBM includes surgery, followed by chemotherapy and radiotherapy. Despite these treatment options, tumour relapse is still a major issue hence the need for cheap and effective treatment strategies. South Africa is endowed with numerous medicinal plants including Sutherlandia frutescens (S.  frutescens) and Carpobrotus edulis (C.edulis), which has been previously reported for their antioxidant and neuroprotective activities. Accordingly, this study was designed to investigate the cytotoxicity of both medicinal plants (S. frutescens and C. edulis) in malignant human GBM cells U251 and U87. The cytotoxic activity was measured using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay while the effect of extracts on colony formation and survival was determined using clonogenic assay. Results show that both S. frutescens and C .edulis induced cytotoxicity in both GBM cells and inhibit colony formation in U251 cells. These findings show that extracts from these plants may be useful in the treatment of GBM and thus requires further investigations into their mechanisms of action as well as isolation of bioactive components responsible for these activities.

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How to Cite
Omoruyi, S. I., Enogieru, A. B., & Ekpo, O. E. (2019). Preliminary Cytotoxic Activity of Sutherlandia frutescens and Carpobrotus edulis on Malignant glioblastoma Cells: doi.org/10.26538/tjnpr/v3i5.5. Tropical Journal of Natural Product Research (TJNPR), 3(5), 175–179. Retrieved from https://tjnpr.org/index.php/home/article/view/1711
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Articles
Author Biography

Adaze B. Enogieru, Department of Medical Biosciences, University of the Western Cape, Robert Sobukwe Road, Private Bag X17, Bellville, 7535, South Africa.

Department of Anatomy, School of Basic Medical Sciences, University of Benin, PMB 1154, Benin City, Nigeria

References

Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, Villano JL. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev. 2014; 23:1985-1996.

Hambardzumyan D and Bergers G. Glioblastoma: Defining Tumor Niches. Trends Cancer 2015; 1:252-265.

Mirimanoff R-O, Gorlia T, Mason W, Van den Bent MJ, Kortmann R-D, Fisher B, Reni M, Brandes AA, Curschmann J, Villa S. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol. 2006; 24:2563-2569.

Ford E, Catt S, Chalmers A, Fallowfield L. Systematic review of supportive care needs in patients with primary malignant brain tumors. Neuro Oncol. 2012; 14:392-404.

Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352:987-996.

Erpolat OP, Akmansu M, Goksel F, Bora H, Yaman E, Büyükberber S. Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: a long-term analysis. Tumori J. 2009; 95:191-197.

Mainardi T, Kapoor S, Bielory L. Complementary and alternative medicine: herbs, phytochemicals and vitamins and their immunologic effects. J Allergy Clin Immunol. 2009; 123:283-294.

Pan S-Y, Zhou S-F, Gao S-H, Yu Z-L, Zhang S-F, Tang M-K, Sun J-N, Ma D-L, Han Y-F, Fong W-F, Ko K-M. New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics. Evid Based Compl Altern Med. 2013; 2013:627375-627375.

Fridlender M, Kapulnik Y, Koltai H. Plant derived substances with anti-cancer activity: from folklore to practice. Front Plant Sci. 2015; 6:799-799.

Balunas MJ and Kinghorn AD. Drug discovery from medicinal plants. Life Sci. 2005; 78:431-441.

Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E, Capaccioli S. Natural compounds for cancer treatment and prevention. Pharmacol Res. 2009; 59:365-378.

van Wyk BE and Albrecht C. A review of the taxonomy, ethnobotany, chemistry and pharmacology of Sutherlandia frutescens (Fabaceae). J Ethnopharmacol. 2008; 119:620-629.

Prevoo D, Smith C, Swart P and Swart A. The effect of Sutherlandia frutescens on steroidogenesis: confirming indigenous wisdom. Endocr Res. 2004; 30:745-751.

Grandi M, Roselli L, Vernay M. Lessertia (Sutherlandia frutescens) and fatigue in oncology. Phytother. 2005; 3:110-113.

Chadwick WA, Roux S, van de Venter M, Louw J, Oelofsen W. Anti-diabetic effects of Sutherlandia frutescens in Wistar rats fed a diabetogenic diet. J Ethnopharmacol. 2007; 109:121-127.

Van Wyk BE. The potential of South African plants in the development of new medicinal products. S Afr J Bot. 2011; 77:812-829.

Skerman NB, Joubert AM, Cronjé MJ. The apoptosis inducing effects of Sutherlandia spp. extracts on an oesophageal cancer cell line. J Ethnopharmacol. 2011; 137:1250-1260.

Vorster C, Stander A, Joubert A. Differential signaling involved in Sutherlandia frutescens-induced cell death in MCF-7 and MCF-12A cells. J Ethnopharmacol. 2012; 140:123-130.

Tai J, Cheung S, Chan E, Hasman D. In vitro culture studies of Sutherlandia frutescens on human tumor cell lines. J Ethnopharmacol. 2004; 93:9-19.

Steenkamp V and Gouws MC. Cytotoxicity of six South African medicinal plant extracts used in the treatment of cancer. S Afr J Bot. 2006; 72:630-633.

Stander A, Marais S, Stivaktas V, Vorster C, Albrecht C, Lottering M-L, Joubert AM. In vitro effects of Sutherlandia frutescens water extracts on cell numbers, morphology, cell cycle progression and cell death in a tumorigenic and a non-tumorigenic epithelial breast cell line. J Ethnopharmacol. 2009; 124:45-60.

Mqoco TV, Visagie MH, Albrecht C, Joubert AM. Differential cellular interaction of Sutherlandia frutescens extracts on tumorigenic and non-tumorigenic breast cells. S Afr J Bot. 2014; 90:59-67.

Lin H, Jackson GA, Lu Y, Drenkhahn SK, Brownstein KJ, Starkey NJ, Lamberson WR, Fritsche KL, Mossine VV, Besch‐Williford CL. Inhibition of Gli/hedgehog signaling in prostate cancer cells by “cancer bush” Sutherlandia frutescens extract. Cell Biol Int. 2016; 40:131-142.

Leisching G, Loos B, Nell T, Engelbrecht AM. Sutherlandia frutescens treatment induces apoptosis and modulates the PI3-kinase pathway in colon cancer cells. S Afr J Bot. 2015; 100:20-26.

Omoruyi S, Enogieru A, Ekpo O. Cytotoxic and apoptosis-inducing effects of Sutherlandia frutescens in neuroblastoma cells. J Afr Assoc Physiol Sci. 2018; 6:136-144.

Johnson Q, Syce J, Nell H, Rudeen K, Folk WR. A randomized, double-blind, placebo-controlled trial of Lessertia frutescens in healthy adults. PLoS Clin Trials. 2007; 2:e16-e16.

Omoruyi BE, Bradley G, Afolayan AJ. Antioxidant and phytochemical properties of Carpobrotus edulis (L.) bolus leaf used for the management of common infections in HIV/AIDS patients in Eastern Cape Province. BMC Compl Altern Med. 2012; 12:215.

Omoruyi B, Bradley G, Afolayan A. Ethnomedicinal survey of medicinal plants used for the management of HIV/AIDS infection among local communities of Nkonkobe Municipality, Eastern Cape, South Africa. J Med Plants Res. 2012; 6:3603-3608.

Martins A, Vasas A, Viveiros M, Molnár J, Hohmann J, Amaral L. Antibacterial properties of compounds isolated from Carpobrotus edulis. Int J Antimicrob Agents. 2011; 37:438-444.

Ibtissem B, Abdelly C, Sfar S. Antioxidant and antibacterial properties of Mesembryanthemum crystallinum and Carpobrotus edulis extracts. Adv Chem Eng Sci. 2012; 2:359-365.

Custódio L, Ferreira AC, Pereira H, Silvestre L, Vizetto-Duarte C, Barreira L, Rauter AP, Alberício F, Varela J. The marine halophytes Carpobrotus edulis L. and Arthrocnemum macrostachyum L. are potential sources of nutritionally important PUFAs and metabolites with antioxidant, metal chelating and anticholinesterase inhibitory activities. Bot Mar. 2012; 55:281-288.

Hafsa J, Hammi KM, Khedher MRB, Smach MA, Charfeddine B, Limem K, Majdoub H. Inhibition of protein glycation, antioxidant and antiproliferative activities of Carpobrotus edulis extracts. Biomed Pharmacother. 2016; 84:1496-1503.

Rocha MI, Rodrigues MJ, Pereira C, Pereira H, da Silva MM, Neng NdR, Nogueira JMF, Varela J, Barreira L, Custódio L. Biochemical profile and in vitro neuroprotective properties of Carpobrotus edulis L., a medicinal and edible halophyte native to the coast of South Africa. S Afr J Bot. 2017; 111:222-231.

Martins A, Vasas A, Schelz Z, Viveiros M, Molnár J, Hohmann J, Amaral L. Constituents of Carpobrotus edulis inhibit P-glycoprotein of MDR1-transfected mouse lymphoma cells. Anticancer Res. 2010; 30:829-835.

Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. cell. 2011; 144:646-674.

Chan P-K. Acylation with diangeloyl groups at C21–22 positions in triterpenoid saponins is essential for cytotoxcity towards tumor cells. Biochem Pharmacol. 2007; 73:341-350.

Pervin S, Singh R, Chaudhuri G. Nitric oxide, Nω-hydroxy-L-arginine and breast cancer. Nitric oxide. 2008; 19:103-106.

Shaik S, Singh N, Nicholas A. HPLC and GC analyses of in vitro-grown leaves of the cancer bush Lessertia (Sutherlandia) frutescens L. reveal higher yields of bioactive compounds. Plant Cell Tissue Organ Cult. 2011; 105:431-438.

Fiebig H, Maier A, Burger A. Clonogenic assay with established human tumour xenografts: correlation of in vitro to in vivo activity as a basis for anticancer drug discovery. Eur J Cancer 2004; 40:802-820.

Narang AS and Desai DS. Anticancer drug development. Pharmaceutical perspectives of cancer therapeutics. Springer, 2009. 49-92 p.

Franken NAP, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc. 2006; 1:2315-2319.

Chakravarti A, Erkkinen MG, Nestler U, Stupp R, Mehta M, Aldape K, Gilbert MR, Black PM, Loeffler JS. Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms. Clin Cancer Res. 2006; 12:4738-4746.

Beier D, Röhrl S, Pillai DR, Schwarz S, Kunz-Schughart LA, Leukel P, Proescholdt M, Brawanski A, Bogdahn U, Trampe-Kieslich A. Temozolomide preferentially depletes cancer stem cells in glioblastoma. Cancer Res. 2008; 68:5706-5715.

Chowdhury K, Sharma A, Kumar S, Gunjan GK, Nag A, Mandal CC. Colocynth Extracts Prevent Epithelial to Mesenchymal Transition and Stemness of Breast Cancer Cells. Front Pharmacol. 2017; 8.

Zhang Z, Feng Y, Li Z-Y, Cao X-Z. Antiproliferative and apoptotic activity of glycyrrhizinic acid in MCF-7 human breast cancer cells and evaluation of its effect on cell cycle, cell migration and m-TOR/PI3K/Akt signalling pathway. Arch Med Sci. 2019; 15:174-182