Investigation of Cytotoxic Effect of Origanum minutiflorum on Cancer Cells

Year 2019, Volume: 6 Issue: 2, 74 - 80, 28.06.2019

OKTAY Özkan , Caner Özbey Işıl Aydemir , İsmail Sari , Gonca Dönmez , Fatma Esin Kırık Ahmet Savran Mehmet İbrahim Tuğlu

https://doi.org/10.34087/cbusbed.405472

Abstract

Objective: Cancer is
defined by a abnormal growth of cells, that invade tissues and organs and
spread to other parts of the body. Breast cancer is one of the most repeatedly
diagnosed cancers and the foremost cause of death among women worldwide. Medicinal
plants can have an anticancerogenic effect in some cancer types. Our aim is to
search the cytotoxic effect of Origanum minutiflorum O.
Schwarz & P.H. Davis on breast cancer cells in vitro conditions.

Methods: In this
study, MDA-MB-231 and MCF-7 breast cancer cell lines and adipose tissue derived
mesenchymal stem cells were used. Essential oil from Origanum
minutiflorum was exposed to
the all cells and IC50 dose was calculated by MTT assay. We have examined
immunocytochemical staining of eNOS, p53, PCNA and TUNEL at IC50 dose for each
cells. The results were evaluated using one-way-ANOVA by Graphpad software.

Results: The
proliferation of breast cancer cells were inhibited by oregano oil. Oregano oil
did not show any cytotoxic effect in mesenchymal stem cells. It was determined
that cytotoxic effect of oregano oil on cancer cells was occurred through
increase of eNOS and p53 staining for survival and the TUNEL labeling for
apoptosis, and decreased of PCNA staining for proliferation.

Conclusion: According
to our data, oregano oil has cytotoxic effect on MDA-MB-231 and MCF-7 breast
cancer cell lines, and it needs to be analysis to detect active components for
other biological activities.

Keywords

Breast cancer; MCF-7; MDA-MB-231; Origanum minutiflorum; cytotoxicity; oxidative stress; apoptosis

Kanser hücreleri üzerine Origanum minutiflorum’un Sitotoksik Etkisinin Araştırılması

Abstract

Amaç: Kanser, doku
ve organları istila eden ve vücudun diğer kısımlarına sıçrayabilen, hücrelerin
anormal gelişimidir. Meme kanseri en çok tekrarlanan tanıya sahip ve dünya
genelinde kadınlarda kanserle ilişkili ölümlerde en önde gelen sebeplerdendir.
Tıbbi bitkiler bazı kanser türlerinde antikarsinojenik özelliklere sahip
olabilmektedir. Bu çalışmanın amacı Origanum
minutiflorum O. Schwarz & P.H. Davis’in in vitro şartlarda, meme kanseri hücre dizilerinde sitotoksik
etkisini araştırmaktır.

Gereç ve
Yöntem: Bu çalışmada, MDA-MB-231 ve MCF-7 meme kanseri hücre dizileri ve adipoz
dokudan izole edilmiş mezenkimal kök hücreleri kullanıldı. Origanum minutiflorum’dan elde edilmiş esansiyel yağa maruz
bırakılmış tüm hücre dizilerinde MTT testi aracılığıyla IC50 dozu hesaplandı. Her
bir hücre dizisinin IC50 dozunda  eNOS,
p53, PCNA ve TUNEL için immunositokimya boyaması yapıldı. Sonuçlar Graphpad
yazılımı kullanılarak one-way-ANOVA kullanılarak değerlendirildi.

Bulgular: Meme
kanseri hücrelerinin proliferasyonu oragano yağı tarafından inhibe edildi.
Oregano yağı mezenkimal kök hücrelerinde herhangi bir sitotoksik etki
göstermedi. eNOS ve p53 ile apoptozisin göstergesi TUNEL’de artış yoluyla
oreagono yağının kanser hücrelerinde sitotoksik olduğu ortaya çıktı ve
PCNA boyamada proliferasyonun azaldığı tespit edildi. Sonuç: Bizim verilerimize göre oregano yağı MDA-MB-231 ve MCF-7 meme
kanseri hücrelerinde sitotoksik bir etkiye sahiptir ve diğer biyolojik
aktiviteleri için aktif komponentlerini tanımlayacak testlere ihtiyaç vardır. 

Keywords

Meme kanseri, MCF-7, MDA-MB-231, Origanum minutiflorum, sitotoksisite, oksidatif stres

References

• Maioral MF, Camila do Nascimento Bodack CN, Stefanes NM, Bigolin A, Mascarello A, Chiaradia-Delatorre LD, Yunes RA, Nunes RJ, Santos-Silva MC. Cytotoxic effect of a novel naphthylchalcone against multiple cancer cells focusing on hematologic malignancies. Biochimie. 2017; 140:48-57.
• Turan I, Demir S, Kilinc K, Yaman SO, Misir S, Kara H, Genc B, Mentese A, Aliyazicioglu Y, Deger O. Cytotoxic effect of rosa canina extract on human colon cancer cells through repression of telomerase expression. Journal of Pharmaceutical Analysis. 2017; doi.org/10.1016/j.jpha.2017.12.005
• Enkhtaivan G, Kim DH, Pandurangan M. Cytotoxic effect of TDZ on human cervical cancer cells. Photoch Photobio B. 2017;173:493–8.
• Perumalsamya H, Sankarapandian K, Kandaswamy N, Balusamy SR, Periyathambi D, Raveendiran N. Cellular effect of styrene substituted biscoumarin caused cellular apoptosis and cell cycle arrest in human breast cancer cells. Int J Biochem Cell B. 2017; 92:104–14.
• Costa Araldi IC, Bordin FPR, Cadoná FC, Barbisan F, Azzolin VF, Teixeira CF, Baumhardt T, Cruz IBM, Duarte MMMF, Bauermann LF. The in vitro radiosensitizer potential of resveratrol on MCF-7 breast cancer cells. Chem-Biol Interact. DOI: 10.1016/j.cbi.2018.01.013
• Maryam R, Faegheh S, Majid AS, Kazem NK. Effect of quercetin on secretion and gene expression of leptin in breast cancer. J Tradit Chin Med 2017; 37(3): 321-5.
• Schnitt SJ, Lakhani SR, Benjamin O. Anderson BO, Mathew BS, Rajkumar T. Breast cancer. In: STEWART BW, WILD CP, ed. World Cancer Report 1st ed. Lyon: Naturaprint, 2014; 362-73.
• Saueressig S, Tessmann J, Mastelari R, Pereira da Silva L, Buss J, Segatto NV, Begnini KR, Pacheco B, Pereira de Pereira CM, Collares T, Seixas FK. Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype. Biomed Pharmacother. 2018; 98: 390–8.
• Park EJ, Lee D, Baek SE, Kim KH, Kang KS, Jang TS, Lee HL, Song JH, Yoo JE. Cytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells. Bioorg Med Chem Lett . 2017; 27: 4389–92.
• Subash-Babu P, Li DK, Alshatwi AA. In vitro cytotoxic potential of friedelin in human MCF-7 breast cancer cell: Regulate early expression of Cdkn2a and pRb1, neutralize mdm2-p53 amalgamation and functional stabilization of p53. Exp Toxicol Pathol. 2017; 69: 630–6.
• Cevatemre B, Botta B, Mori M, Berardozzi S, Ingallina C, Ulukaya E. The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro. Chem Biol Interact. 2016; 260: 248-55.
• Zarei O, Yaghoobi MM. Cytotoxic effects of Fritillaria imperialis L. extracts on human liver cancer cells, breast cancer cells and fibroblast-like cells. Biomed Pharmacother. 2017; 94: 598–604.
• Kumari S, Badana AK, Mohan GM, Naik GS, Malla RR. Synergistic effects of coralyne and paclitaxel on cell migration and proliferation of breast cancer cells lines. Biomed Pharmacother. 2017; 91: 436-45.
• Vukovic NL, Obradovic AD, Vukic MD, Jovanovic D, Djurdjevic PM. Cytotoxic, proapoptotic and antioxidative potential of flavonoids isolated from propolis against colon (HCT-116) and breast (MDA-MB-231) cancer cell lines. Food Res Int. 2018; 106: 71–80.
• Brito LC, Berenger ALR, Figueiredo MR. An overview of anticancer activity of Garcinia and Hypericum. Food Chem Toxicol . 2017; 109: 847-62.
• Hajlaoui H, Mighri H, Aouni M, Gharsallah N, Kadri A. Chemical composition and in vitro evaluation of antioxidant, antimicrobial, cytotoxicity and anti- acetylcholinesterase properties of Tunisian Origanum majorana L. essential oil. Microb Pathog. 2016; 95: 86-94.
• Bouyahya A, Bakri Y, Et-Touys A, Assemian ICC, Abrini J, Dakka N. In vitro antiproliferative activity of selected medicinal plants from the North-West of Morocco on several cancer cell lines. Eur J Integr Med .2018; 18: 23–9.
• Bostancıoğlu RB, Kurkcuoğlu M, Başer KHC, Koparal AT. Assessment of anti-angiogenic and anti-tumoral potentials of Origanum onites L. essential oil. Food Chem Toxicol. 2012; 50: 2002–8.
• Han X, Parker TL. Anti-inflammatory, tissue remodeling, immunomodulatory, and anticancer activities of oregano (Origanum vulgare) essential oil in a human skin disease model. Biochim Open. 2017; 4: 73-7.
• Abdel-Massih RM, Fares R, Bazzi S, El-Chami N, Baydoun E. The apoptotic and anti-proliferative activity of Origanum majorana extracts on human leukemic cell line. Leuk Res . 2010; 34: 1052–6.
• Al-Kalaldeh JZ, Abu-Dahab R, Afifi FU. Volatile oil composition and antiproliferative activity of Laurus nobilis, Origanum syriacum, Origanum vulgare, and Salvia triloba against human breast adenocarcinoma cells. Nutr Res . 2010; 30: 271–8.
• Baydar H. Yayla kekiği (origanum minutiflorum o. schwarz et. p. h. davis)'nde farklı toplama zamanlarının uçucu yağ içeriği ve uçucu yağ bileşenleri üzerine etkisi. Mediterr Agric Sci. 2005;18(2): 175-8.
• Tuğlu Mİ, Özdal-Kurt F, Koca H, Sarac A, Barut T, Kazanç A. The Contribution of Differentiated Bone Marrow Stromal Stem CellLoaded Biomaterial to Treatment in Critical Size Defect Model in Rats. Kafkas Univ Vet Fak Derg. 2010; 16 (5): 783-92.
• Uluer ET, Aydemir I, Inan S, Ozbilgin K, Vatansever HS. Effects of 5-fluorouracil and gemcitabine on a breast cancer cell line (MCF-7) via the JAK/STAT pathway. Acta Histochem. 2012;114(7):641-6.
• Deliloglu GI, Tuglu I, Vatansever HS, Ozdal-Kurt F, Ekren H, Taylan M, Sen BH. The effect of osteogenic medium on the adhesion of rat bone marrow stromal cell to the hydroxyapatite. Saudi Med J. 2006; 27(3):305-11.
• Kurt FÖ, Tuğlu I, Vatansever HS, Tong S, Şen BH, Deliloğlu-Gürhan SI. The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts. Biotech Histochem. 2016; 91(6):412-22.
• Karabuga I, Akbay K, Turna B, Vatansever HS, Altay B, Güzel E, Turkoz Uluer E,Ustun G, Ekren F, Nazli O, Muftuoglu S, Apaydin E. Effect of lisinopril on renal tissue damage in unilateral ureteral obstruction in rats. Urol Res. 2012; 40(1):27-34.
• Gürpınar T, Ekerbiçer N, Uysal N, Barut T, Tarakçı F, Tuglu MI. The effects of the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain. ScientificWorldJournal. 2012; 2012:498489.
• Ozbilgin K, Karaca F, Turan A, Köse C, Vatansever S, Ozcakir T. The higher heparin-binding epidermal growth factor (HB-EGF) in missed abortion. Taiwan J Obstet Gynecol. 2015; 54(1):13-8.
• Hack CC, Voiß P, Lange S, Paul AE, Conrad S, Dobos GJ, Beckmann MW, Kümmel S. Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine. Geburtshilfe Frauenheilkd. 2015;75(7):675-82.
• Kim W, Lee WB, Lee JW, Min BI, Baek SK, Lee HS, Cho SH. Traditional herbal medicine as adjunctive therapy for breast cancer: A systematic review. Complement Ther Med. 2015;23(4):626-32.
• Zheng J, Zhou Y, Li Y, Xu DP, Li S, Li HB. Spices for Prevention and Treatment of Cancers. Nutrients. 2016;8(8): E495.
• Tariq A, Sadia S, Pan K, Ullah I, Mussarat S, Sun F, Abiodun OO, Batbaatar A, Li Z, Song D, Xiong Q, Ullah R, Khan S, Basnet BB, Kumar B, Islam R, Adnan M. A systematic review on ethnomedicines of anti-cancer plants. Phytother Res. 2017;31(2):202-64.
• Moore J, Yousef M, Tsiani E. Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols. Nutrients. 2016;8(11): E731
• Santos PA, Avanço GB, Nerilo SB, Marcelino RI, Janeiro V, Valadares MC, Machinski M. Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalis L.), Turmeric (Curcuma longa L.), and Ginger (Zingiber officinale R.) Essential Oils in Cervical Cancer Cells (HeLa). ScientificWorldJournal. 2016;2016:9273078.
• Zaker A, Asili J, Abrishamchi P, Tayarani-Najaran Z, Mousavi SH. Cytotoxic and apoptotic effects of root extract and tanshinones isolated from Perovskiaabrotanoides Kar. Iran J Basic Med Sci. 2017;20(12):1377-84.
• Rolim TL, Meireles DRP, Batista TM, de Sousa TKG, Mangueira VM, de Abrantes RA, Pita JCLR, Xavier AL, Costa VCO, Batista LM, da Silva MS, Sobral MV. Toxicity and antitumor potential of Mesosphaerum sidifolium (Lamiaceae) oil and fenchone, its major component. BMC Complement Altern Med. 2017 Jul 3;17(1):347.
• Fekrazad R, Afzali M, Pasban-Aliabadi H, Esmaeili-Mahani S, Aminizadeh M, Mostafavi A. Cytotoxic Effect of Thymus caramanicus Jalas on Human Oral Epidermoid Carcinoma KB Cells. Braz Dent J. 2017; 28(1):72-7.
• Oke F, Aslim B. Biological potentials and cytotoxicity of various extracts from endemic Origanum minutiflorum O. Schwarz & P.H. Davis. Food Chem Toxicol. 2010;48(6):1728-33.
• Dadalioglu I, Evrendilek GA. Chemical compositions and antibacterial effects of essential oils of Turkish oregano (Origanum minutiflorum), bay laurel (Laurus nobilis), Spanish lavender (Lavandula stoechas L.), and fennel (Foeniculum vulgare) on common foodborne pathogens. J Agric Food Chem. 2004;52(26):8255-60.
• Dorman HJ, Bachmayer O, Kosar M, Hiltunen R. Antioxidant properties of aqueous extracts from selected lamiaceae species grown in Turkey. J Agric Food Chem. 2004;52(4):762-70.
• Cetin- H, Yanikoglu A. A study of the larvicidal activity of Origanum (Labiatae) species from southwest Turkey. J Vector Ecol. 2006; 31(1):118-22.
• Cetin H, Cilek JE, Aydin L, Yanikoglu A. Acaricidal effects of the essential oil of Origanum minutiflorum (Lamiaceae) against Rhipicephalus turanicus (Acari: Ixodidae). Vet Parasitol. 2009; 160(3-4):359-61.
• Süntar I, Akkol EK, Keleş H, Oktem A, Başer KH, Yeşilada E. A novel wound healing ointment: a formulation of Hypericum perforatum oil and sage and oregano essential oils based on traditional Turkish knowledge. J Ethnopharmacol. 2011; 134(1):89-96.
• Akdemir Evrendilek G. Empirical prediction and validation of antibacterial inhibitory effects of various plant essential oils on common pathogenic bacteria. Int J Food Microbiol. 2015; 202:35-41.