Clinopodium serpyllifolium subsp. serpyllifolium Bitkisinin Akciğer Kanseri ve Beyin Glioma Hücre Hatlarında Antikanser, Antiproliferatif ve Apoptotik Hücre Ölümü Üzerine Etkilerinin Araştırılması

Sevgi Gezici; Didem Kocum; Fatih Yayla; Nazım Şekeroğlu

doi:10.18016/ksutarimdoga.vi.959044

EN TR

Investigation of Anticancer, Antiproliferative and Apoptotic Cell Death Effects of Clinopodium serpyllifolium subsp. serpyllifolium in Lung and Brain Glioma Cell Lines

Abstract

In this study, it was aimed to investigate cytotoxic, antiproliferative and apoptotic activities of Clinopodium serpyllifolium subsp. serpyllifolium, which grows naturally in the flora of Turkey and has been widely used in traditional folk medicine thanks to its rich phytochemical content. For this purpose, water (dH2O) ve 70% ethanol (C2H5OH-EtOH) extracts were obtained from flower and stems of the plants using different solvents. The activities of different extracts on the anticancer, antiproliferation and DNA damage-based apoptosis activities against A549, H1299, C6 and HUVEC cells using MTT, trypan blue and immunological-based ELISA methods, respectively. It was determined that plant extracts decreased viability of all the cells and induced these cells to die. The extracts showed the highest activity against the A549 lung carcinoma cells, whilst they showed the lowest activity against the C6 brain glioma cells. In conclusion, it is considered that different parts of the C. serpyllifolium should be phytochemically investigated in details, pharmacological and clinical studies ought to be carried out in order to use this plant as anticancer drug source.

Keywords

Clinopodium serpyllifolium subsp. serpyllifolium Bitkisinin Akciğer Kanseri ve Beyin Glioma Hücre Hatlarında Antikanser, Antiproliferatif ve Apoptotik Hücre Ölümü Üzerine Etkilerinin Araştırılması

Öz

Bu çalışmada, Türkiye florasında doğal olarak yetişen ve zengin fitokimyasal içeriği sayesinde geleneksel halk tıbbında yaygın olarak kullanılan Clinopodium serpyllifolium subsp. serpyllifolium bitkisinin sitotoksik, antiproliferatif ve apoptotik aktivitelerinin araştırılması amaçlanmıştır. Bu amaçla, bitkinin çiçek ve gövde kısımlarından su (dH2O) ve %70’lik etanol (C2H5OH-EtOH) çözücüleri kullanılarak ekstraktlar elde edilmiştir. Farklı ekstraktların antikanser, antiproliferizasyon ve DNA hasarı gelişimi üzerine apoptotik aktiviteleri; A549, H1299, C6 ve HUVEC hücrelerine karşı sırasıyla MTT, tripan mavisi ve immünolojik temelli ELISA yöntemleri kullanılarak analiz edilmiştir. Bitki ekstrelerinin, çalışılan kanser hücre hatlarının her üçünde de hücrelerdeki canlılık oranlarını azaltarak, hücreleri ölüme teşvik ettiği saptanmıştır. Ekstreler, en yüksek aktiviteyi A549 akciğer karsinoma hücrelerine karşı; en düşük aktiviteyi ise C6 beyin glioma hücreleri üzerine göstermiştir. Sonuç olarak, C. serpyllifolium bitkisinin çiçek ve gövde kısımlarının fitokimyasal içeriğinin belirlenmesi ve bitkinin antikanser drog olarak kullanımına yönelik farmakolojik ve klinik çalışmaların yapılması gerekmektedir.

Anahtar Kelimeler

Supporting Institution

: Sunulan çalışma Kilis 7 Aralık Üniversitesi, Bilimsel Araştırma Projeleri (BAP) Yönetim Birimi tarafından finansal olarak desteklenmiştir.

Project Number

Proje kodu: 1928MAP1

Thanks

Teşekkürler: Sunulan çalışma Kilis 7 Aralık Üniversitesi, Bilimsel Araştırma Projeleri (BAP) Yönetim birimi tarafından finansal olarak desteklenmiştir (Proje kodu: 1928MAP1).

References

Abdulridha MK, Al-Marzoqi AH, Al-Awsi GRL, Mubarak SM, Heidarifard M, Ghasemian A 2020. Anticancer effects of herbal medicine compounds and novel formulations: a literature review. Journal of Gastrointestinal Cancer. 51: 765-773
Ali-Shtayeh MS, Jamous RM 2008. Traditional Arabic Palestinian Herbal Medicine, TAPHM. Til, Nablus, Palestine, Biodiversity and Environmental Research Center, BERC. ISBN 978-9950-324-04-6
Ali-Shtayeh MS, Jamous RM, Abu-Zaitoun SY, Akkawi RJ, Kalbouneh SR, Bernstein N, Dudai, N 2018. Chemical profile and bioactive properties of the essential oil isolated from Clinopodium serpyllifolium (M. Bieb.) Kuntze growing in Palestine. Industrial Crops and Products 124: 617-625.
Barboza GE, Cantero JJ, Núñez C, Ariza Espinar L, Pacciaroni ADV 2009. Medicinal plants: A general review and a phytochemical and ethnopharmacological screening of the native Argentine Flora. Kurtziana. 34(1): 12-20.
Batsalova T, Bardarov K, Bardarov V, Moten D, Dzhambazov, B 2017. Cytotoxic properties of Clinopodium vulgare L. extracts on selected human cell lines. Comptes Rendus l’Académie Bulgarian Des Science. 70(5): 645-650.
Baydar H 2020. Tıbbi ve aromatik bitkiler bilimi ve teknolojisi. (8.baskı). Nobel Akademik Yayınları, Ankara, 21 sy.
Baytop T 1999. Türkiye'de bitkiler ile tedavi: geçmişte ve bugün. (1.baskı). Nobel Tıp Kitabevleri.
Bruno MJ, Onreshkova D, Simeonov S, Naidenova E, Pencheva I 2019. Analysis and identification of flavanoids and phenolcarbonic acid in extract plant of Clinopodium vulgare. American Journal of Analytical Chemistry. 10(12): 641.

Carvajal F, Huanca A, González-Teuber M, Urzúa A, Echeverría J 2017. Uses of hazardous medicinal plants: composition of the essential oil of Clinopodium gilliesii (Benth.) Kuntze (Lamiaceae), collected in Chile. Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas. 16(5): 486-492.
Ćavar S, Vidic D, Maksimović M 2013. Volatile constituents, phenolic compounds, and antioxidant activity of Calamintha glandulosa (Req.) Bentham. Journal of the Science of Food and Agriculture. 93(7): 1758-1764.
Dunkić V, Kremer D, Grubešić RJ, Rodríguez JV, Ballian D, Bogunić F, Stabentheiner E 2017. Micromorphological and phytochemical traits of four Clinopodium L. species (Lamiaceae). South African Journal of Botany. 111: 232-241.
El-Huneidi W, Shehab NG, Bajbouj K, Vinod A, El-Serafi A, Shafarin J, Abu-Gharbieh E 2020. Micromeria fruticosa induces cell cycle arrest and apoptosis in breast and colorectal cancer cells. Pharmaceuticals. 13(6): 115.
Gezici S, Sekeroglu N 2022. Comparative biological analyses on kenger and kenger coffee as novel functional food products. Journal of Food Science and Technology. 59(6): 2328-2338.
Gezici S 2019. Comparative anticancer activity analysis of saffron extracts and a principle component, crocetin for prevention and treatment of human malignancies. Journal of Food Science and Technology. 56(12): 5435-5443.
Gezici S, Sekeroglu N 2019a. Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents. Anti-Cancer Agents in Medicinal Chemistry. 19(1): 101-111.
Gezici S, Sekeroglu N 2019b. Neuroprotective potential and phytochemical composition of acorn fruits. Industrial Crops and Products. 128: 13-17.
Gezici S, Sekeroglu N, Kijjoa A 2017. In vitro anticancer activity and antioxidant properties of essential oils from Populus alba L. and Rosmarinus officinalis L. from South Eastern Anatolia of Turkey. Indian Journal of Pharmaceutical Education and Research. 51(3): 498-503.
Greenwell M, Rahman PKSM 2015. Medicinal plants: their use in anticancer treatment. International Journal of Pharmaceutical Sciences and Research. 6(10): 4103.
Hanahan D, Weinberg RA 2011. Hallmarks of cancer: the next generation. Cell. 144(5): 646-674.
Harley RM, Paucar AG 2000. List of species of tropical American Clinopodium (Labiatae), with new combinations. Kew Bulletin. 917-927.
Hingst O, Blottner S 1995. Quantification of apoptosis (programmed cell death) in mammalian testis by DNA-fragmentation ELISA. Theriogenology. 44(3): 313-319.
Jaramillo BE, Stashenko E, Martínez JR 2010. Volatile chemical composition of the Colombian Satureja brownei (Sw.) Briq. and determination of its antioxidant activity. Revista Cubana de Plantas Medicinales. 15(1): 52-63.
Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, Castanas E 2004. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Research. 6(2): 1-12.
Kaya A 2019. Morphological characteristics of Clinopodium acinos and Clinopodium suaveolens (Lamiaceae) growing in Turkey. Journal of Research in Pharmacy. 23(1): 62-68.
Kılıc O, Kutlu MA, Özdemir FA 2017. Essential oil composition of Clinopodium vulgare L. subsp. arundanum (Boiss.) Nyman from Bingöl (Turkey). International Journal of Secondary Metabolite. 4(3, Special Issue 1): 11-15.
Kladniew BR, Polo M, Villegas SM, Galle M, Crespo R, Bravo MG 2014. Synergistic antiproliferative and anticholesterogenic effects of linalool, 1, 8-cineole, and simvastatin on human cell lines. Chemico-biological Interactions. 214: 57-68.
Koc K, Ozdemir O, Kizilkaya OF, Sengul M, Turkez H 2017. Cytotoxic activity of the aqueous extract of Micromeria fruticosa (L.) Druce subsp. serpyllifolia on human U-87 MG cell lines. Archives of Biological Sciences. 69(3): 449-453.
Lampronti I, Saab AM, Gambari R 2006. Antiproliferative activity of essential oils derived from plants belonging to the Magnoliophyta division. International Journal of Oncology. 29(4): 989-995.
Ludeña HMA. 2017. Método preparativo de ácido ursólico a partir de la planta de medicinal Flor de arena (Clinopodium revolutum) (Doctoral dissertation, Pontificia Universidad Catolica del Peru-Centrum Catolica Peru.
Mahady GB 2005. Medicinal plants for the prevention and treatment of bacterial infections. Current Pharmaceutical Design. 11(19): 2405-2427.
Matailo A, Bec N, Calva J, Ramírez J, Andrade JM, Larroque C, Armijos C 2019. Selective BuChE inhibitory activity, chemical composition, and enantiomer content of the volatile oil from the Ecuadorian plant Clinopodium brownei. Revista Brasileira de Farmacognosia. 29(6): 749-754.
Mohanty S, Kamolvit W, Zambrana S, Sandström C, Gonzales E, Östenson CG, Brauner A 2017. Extract of Clinopodium bolivianum protects against E. coli invasion of uroepithelial cells. Journal of Ethnopharmacology. 198: 214-220.
Mossman B, Light W, Wei E 1983. Asbestos: mechanisms of toxicity and carcinogenicity in the respiratory tract. Annual Review of Pharmacology and Toxicology. 23(1): 595-615.
Mutalib M A, Ali F, Othman F, Ramasamy R, Rahmat A 2016. Phenolics profile and anti-proliferative activity of Cyphomandra Betacea fruit in breast and liver cancer cells. SpringerPlus. 5(1): 1-13.
Pino J A, Estarrón M, Fuentes V 1997. Essential oil of Satureja brownei (Sw.) Briq. grown in Cuba. Journal of Essential Oil Research. 9(5): 595-596.
Ramakrishna W, Kumari A, Rahman N, Mandave P 2021. Anticancer activities of plant secondary metabolites: Rice callus suspension culture as a new paradigm. Rice Science. 28(1): 13-30.
Roy A, Jauhari N, Bharadvaja N 2018. 6 Medicinal Plants as. Anticancer Plants: Natural Products and Biotechnological Implements. 2: 109.
Russo A, Formisano C, Rigano D, Cardile V, Arnold NA, Senatore F 2016. Comparative phytochemical profile and antiproliferative activity on human melanoma cells of essential oils of three lebanese Salvia species. Industrial Crops and Products. 83: 492-499.
Salameh N, Shraim N, Jaradat N 2018. Chemical composition and enzymatic screening of Micromeria fruticosa serpyllifolia volatile oils collected from three different regions of West Bank, Palestine. BioMed Research International. 2018: 1-8.
Salameh N, Shraim N, Jaradat N, El Masri M, Adwan L, K’aibni S, AbuAlhasan M 2020. Screening of antioxidant and antimicrobial activity of Micromeria fruticosa serpyllifolia volatile oils: A comparative study of plants collected from different regions of west bank, Palestine. BioMed Research International. 2020: 1-7.
Saldaña-Bobadilla V, Ramirez JK, Perez-Chauca E, Minchan-Herrera P 2020. Tiquilia paronychioides (Phil.) at Richardson (Boraginaceae): Una revisión etnobotánica, etnofarmacológica toxicológica. Ethnobotany Research and Applications. 19: 1-13.
Searle J, Kerr JF, Bishop CJ 1982. Necrosis and Apoptosis Distinct Modes Death With Fundamentally Different Significance. Pathol Annu. 17: 229-259.
Senol FS, Sekeroglu N, Gezici S, Kilic E, Orhan, IE 2018. Neuroprotective potential of the fruit (acorn) from Quercus coccifera L. Turkish Journal of Agriculture and Forestry. 42(2): 82-87.
Shehab NG, Abu-Gharbieh E 2012. Constituents and biological activity of the essential oil and the aqueous extract of Micromeria fruticosa (L.) Druce subsp. serpyllifolia. Pakistan Journal of pharmaceutical Sciences. 25(3): 687-692.
Smith JH, Simons C 2004. Development of enzyme inhibitors as drugs. Enzymes and their inhibitors. Drug Development. 190-328.
Sobral MV, Xavier AL, Lima TC, Sousa DP 2014. Antitumor activity of monoterpenes found in essential oils. The Scientific World Journal. 95: 1-35.
Solís Quispe L, Pino JA, Tomaylla-Cruz C, Solís Quispe JA, Aragón-Alencastre LJ, Solís Quispe A 2018. Chemical composition and larvicidal activity of the essential oils from Minthostachys spicata (Benth.) Epling and Clinopodium bolivianum (Benth) Kuntze against Premnotrypes latithorax Pierce. American Journal of Essential Oils and Natural Products. 6(2): 22-28.
Strober W 2015. Trypan blue exclusion test of cell viability. Current Protocols in Immunology, 111(1): 1-2.
Sung H, Ferlay J., Siegel R L, Laversanne M, Soerjomataram I, Jemal A, Bray F 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer Journal for Clinicians. 71(3): 209-249.
Telci I, Ceylan M 2007. Essential oil composition of Micromeria fruticosa Druce from Turkey. Chemistry of Natural Compounds. 43(5): 629-631.
Tewary P, Gunatilaka AL, Sayers TJ 2017. Using natural products to promote caspase-8-dependent cancer cell death. Cancer Immunology, Immunotherapy. 66(2): 223-231.
The Plant List 2021. (http://www.theplantlist.org/)
Tomas J, Gil L, Llorens-Molina JA, Cardona C, Garcia MT, Llorens L 2019. Biogenic volatiles of rupicolous plants act as direct defenses against molluscs: The case of the endangered Clinopodium rouyanum. Flora. 258: 151428.
Tošić S, Stojičić D, Stankov-Jovanovic V, Mitic V, Mihajilov-Krstev T, Zlatkovic B 2015. Chemical composition, antioxidant and antimicrobial activities of micropropagated and native Micromeria pulegium (Lamiaceae) extracts. Oxidation Communications. 38(1): 55-66.
Gokyigit N 2021. Türkiye Bitkileri Listesi / Nezahat Gökyiğit Botanik Bahçesi 2021. (https://www.bizimbitkiler.org.tr/yeni)
Tuttolomondo T, Licata M, Leto C, Bonsangue G, Gargano ML, Venturella G, La Bella S 2014. Popular uses of wild plant species for medicinal purposes in the Nebrodi Regional Park (North-Eastern Sicily, Italy). Journal of Ethnopharmacology. 157: 21-37.
Vázquez AM, Aimar ML, Demmel GI, Cabalen ME, Decarlini MF, Cantero JJ, Ruiz GM 2014. Identification of volatile compounds of Clinopodium odorum (Lamiaceae): A comparison between HS-SPME and classic hydrodistillation. Boletín latinoamericano y del Caribe de Plantas Medicinales y Aromáticas. 13(3): 285-296.
Yagi S, Babiker R, Tzanova T, Schohn H 2016. Chemical composition, antiproliferative, antioxidant and antibacterial activities of essential oils from aromatic plants growing in Sudan. Asian Pacific Journal of Tropical Medicine. 9(8): 763-770.
Zhang L, Zhao F, Tao A 2020. Characterization of the complete chloroplast genome of Clinopodium chinense (Labiatae), a medicinal plant in southwest of China. Mitochondrial DNA Part B. 5(2): 1491-1493.
Zhang X, Yu Y, Cen Y, Yang D, Qi Z, Hou Z, Liu K 2018. Bivariate correlation analysis of the chemometric profiles of Chinese wild Salvia miltiorrhiza based on UPLC-Qqq-MS and antioxidant activities. Molecules. 23(3): 538-551.
Zheleva-Dimitrova D, Simeonova R, Gevrenova R, Savov Y, Balabanova V, Nasar-Eddin G, Danchev N 2019. In vivo toxicity assessment of Clinopodium vulgare L. water extract characterized by UHPLC-HRMS. Food and Chemical Toxicology. 134: 110841.

Details

Primary Language

Turkish

Subjects

Structural Biology

Journal Section

Research Article

Authors

Sevgi Gezici ^*
0000-0002-4856-0221
Türkiye

Didem Kocum
0000-0003-2519-0608
Türkiye

Fatih Yayla
0000-0002-6490-6288
Türkiye

Nazım Şekeroğlu
0000-0002-0630-0106
Türkiye

Publication Date

October 31, 2022

Submission Date

June 29, 2021

Acceptance Date

September 2, 2021

Published in Issue

Year 2022 Volume: 25 Number: 5

DOI

https://doi.org/10.18016/ksutarimdoga.vi.959044

IZ

https://izlik.org/JA73HA44UW

Cite

RIS / Bibtex

APA

Gezici, S., Kocum, D., Yayla, F., & Şekeroğlu, N. (2022). Clinopodium serpyllifolium subsp. serpyllifolium Bitkisinin Akciğer Kanseri ve Beyin Glioma Hücre Hatlarında Antikanser, Antiproliferatif ve Apoptotik Hücre Ölümü Üzerine Etkilerinin Araştırılması. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 25(5), 974-985. https://doi.org/10.18016/ksutarimdoga.vi.959044