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Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri

Yıl 2023, Cilt: 11 Sayı: 3, 1517 - 1528, 31.07.2023

Güllü Kaymak Meliha Koldemir Gündüz Ertan Kanbur

https://doi.org/10.29130/dubited.1162385

Öz

Çağımızın en yüksek ölüm oranına sahip sağlık sorunlarından biri olan kanser vakalarının önlenmesi için yeni ve etkili tedavi stratejileri geliştirmeye yönelik araştırmalar son yıllarda önem kazanmıştır. Doğal kaynaklardan elde edilen özütler, uçucu yağlar ve biyoaktif bileşenler daha az yan etki ile etkin tedavi sunma potansiyelindedir. Bu çalışmanın amacı, menengiç meyvesinin ekstraktının hepatoselüler karsinom hücrelerinde (HepG2) oksidatif stres, sitotoksik ve apoptotik etkilerini incelemektir. Sağlıklı karaciğer epitel hücreleri (ZFL) ile elde edilen sonuçlar karşılaştırılarak bu ekstraktın kanser hücrelerine spesifik olup olmadığı değerlendirilmiştir. Literatürde ilk kez yapılan çalışmamızda, soxhlet yöntemi ile menengiç meyvelerinden elde edilen ekstraktın IC50 dozunu ve süresini belirlemek için iCELLigence sistemi, sitotoksisiteyi belirlemek amacıyla MTT yöntemi, apoptoz profilini belirlemek için Anneksin V yöntemi kullanılmıştır. Menengiç ekstraktının oluşturabileceği oksidatif hasarın belirlenmesinde; TAS, TOS, GSH ve lipid peroksidasyon seviyeleri ile NADP-IDH, katalaz, alkalen fosfataz ve asit fosfataz enzim aktivitesi analizleri spektrofotometrik yöntemlerle yapılmıştır. iCELLigence sistemi ile yapılan analiz sonucunda menengiç ekstraktının HepG2 hücrelerindeki 48 saatlik IC50 dozu 419 µg/mL olarak bulunmuştur. Sitotoksisite analizi ile menengiç ekstraktının HepG2 hücrelerinde ZFL hücrelerine kıyasla daha öldürücü olduğu gözlenmiştir. Aynı şekilde HepG2 hücrelerinde 6 saatte gözlenen apoptotik ve ölü hücre sayısı ZFL hücrelerine göre daha fazla olduğu gözlenmiştir. Oksidatif hasarı belirlemek için yapılan analizlerde ZFL hücrelerinde gözlenen sonuçlar istatistiksel olarak anlamlı bulunmazken, HepG2 hücrelerinde hem kontrol grubuyla hem de ZFL hücrelerine kıyasla belirgin oksidatif hasar gözlenmiştir. Elde edilen bulgular, kanser tedavisinde yeni ajanlar geliştirilmesi yönündeki çalışmalara kaynak oluşturabilecektir.

Anahtar Kelimeler

Kanser karaciğer sitotoksisite apoptoz oksidatif stres menengiç.

Destekleyen Kurum

Kütahya Sağlık Bilimleri Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Proje Numarası

TSA-2020-46 numaralı proje

Kaynakça

  • [1] I.T. Agar, N. Kaska and S. Kafkas, “Characterization of lipids in Pistacia species grown in Turkey,” In Acta Horticulturae, pp. 417-422, 1995.
  • [2] E. Ayrancı and A.C. Dalgıç, “Preparation of protein isolates from Pistacia terebinthus L. and examination of some functional properties,” Lebensmittel Wissenschaft Und Technologie, vol. 25, no. 5, pp. 442-444, 1992a.
  • [3] E. Ayrancı and A.C. Dalgıç, “Moisture sorption isotherms of Pistacia terebinthus L. and protein isolate,” Lebensmittel Wissenschaft Und Technologie, vol. 25, no. 5, pp. 482-483, 1992b.
  • [4] L. Bonsignore, F. Cottiglia and G. Loy, “Antibacterial activity of Pistacia lentiscus L. aerial parts,” Fitoterapia, vol. 69, no. 6, pp. 537-538, 1998.
  • [5] T. Baytop, Türkiye' deki Tıbbi Bitkiler İle Terapi, Birinci Baskı, İstanbul, Nobel Tıp Kitabevleri, 1999, 12. Bölüm, 111-117.
  • [6] E. Yeşilada, G. Honda and E. Sezik, “Traditional medicine in Turkey V. Folk Medicine in The Inner Taurus Mountains,” Journal of Ethnopharmacology, vol. 46, pp. 133-155, 1995.
  • [7] M. Couladis, M. Özcan, O. Tzakou and A. Akgül, “Comparative essential oil composition of various parts of the turpentine tree (Pistacia terebinthus L.) growing wild in Turkey,” Journal of the Science of Food and Agriculture, vol. 83, pp. 136-138, 2003.
  • [8] M.M. Özcan, O. Tzakou and M. Couladis, “Essential oil composition of the turpentine tree (Pistacia terebinthus L.) fruits growing wild in Turkey,” Food Chemistry, vol. 114, no. 1, pp 282-285, 2009.
  • [9] L. Dalgiç, S.O. Sermet ve G. Özkan, “Farklı kavurma sıcaklıklarının menengiç yağ kalite parametreleri üzerine etkisi,” Akademik Gıda, c. 9, s. 3, ss. 26-36, 2011.
  • [10] E.M. Giner-Larza, S. Ma´nez, M.C. Recio, R.M. Giner, J.M. Prieto and M. Cerda´-Nicola´s, “Oleanolic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity,” Eur. J. Pharmacol, vol. 428, pp. 137-143, 2001.
  • [11] T. Bakirel, S. Sener, U. Bakirel, O. Keles, G. Sennazli and A. Gurel, “The investigation of the effects of P. terebinthus L. upon experimentally induced hypercholesterolemia and atherosclerosis in rabbits,” Turkish Journal of Veterinary Sciences, vol. 27, pp. 1283-1292, 2003.
  • [12] F. Tetik, S. Civelek and U. Cakilcioglu, “Traditional Uses of Some Medicinal Plants in Malatya (Turkey),” Journal of Ethnopharmacology, vol. 146, no. 1, pp. 331-346, 2013.
  • [13] K. Canli, A. Yetgin, I. Akata and E.M. Altuner, “Antimicrobial Activity and Chemical Composition Screening of Epilobium montanum Root,” Indian Journal of Pharmaceutical Education and Research, vol. 51, no. 3, pp. 239-243, 2017.
  • [14] M.E. Bozyel, M. Şenturan, A. Benek, E. Merdamert Bozyel, K. Canli and E.M Altuner, “In Vitro Antimicrobial Activity Screening of Heliotropium europaeum Against Wide Range of Microorganisms and Multi Drug Resistant (Mdr) Bacteria,” European Journal of Biomedical and Pharmaceutical Sciences, vol. 6, no. 3, pp. 113-117, 2019.
  • [15] H.B. El‐Serag, “Epidemiology of hepatocellular carcinoma,” The Liver: Biology and Pathobiology, pp. 758-772, 2020.
  • [16] A. Yerlikaya, E. Erdoğan, E. Okur, Ş. Yerlikaya and B. Savran, “A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib,” Oncology Letters, vol. 12, no. 1, pp. 323-330, 2016.
  • [17] O. Erel, “A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation,” Clinical biochemistry, vol. 37, no. 4, pp. 277-285, 2004.
  • [18] O. Erel, “A new automated colorimetric method for measuring total oxidant status,” Clinical Biochemistry, vol. 38, no. 12, pp. 1103-1111, 2005.
  • [19] M. Koldemir Gündüz, “BGM a Newly Synthesised Boron Compound, Induces Apoptosis and Reduces Oxidative Stress by Inhibiting Lipogenesis in 3T3-L1 Adipocytes via PPARγ and CTRP3,” Biol Trace Elem Res, 2022, in press.
  • [20] H. Aebi, “Catalase Invitro. In: Methods of Enzymatic Analysis,” Ed: Bergmeyer HU, FL, 2nd ed, pp. 121- 126, 1974.
  • [21] K. Walter and C. Schutt, “Acid and alkaline phosphatase in serum,” Methods of Enzymatic Analysis, vol. 2, pp. 856-860, 1974.
  • [22] A. Ledwozyw, D. Michalak, A. Stepien and A. Kadziolka, “The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis,” Clin Chim Acta, vol. 155, no. 3, pp. 275-283, 1986.
  • [23] E. Beutler, “Glutathione in red cell metabolism: a manual of biochemical methods”, 2nd ed., Grune and Stratton, NY, pp. 112-114, 1975.
  • [24] Z. Selamoğlu, “Polyphenolic Compounds in Human Health with Pharmacological Properties”, Journal of Traditional Medicine Clinical Naturopathy, vol. 6, no. 4, pp.137, 2017.
  • [25] Z. Selamoğlu, “Biotechnological Approaches on Anticancer Activity of Flavonoids”, Modern Approaches in Drug Designing, vol. 1, no. 2, pp. 510, 2017.
  • [26] G. Topçu, M. Ay, A. Bilici, C. Sarıkürkçü, M. Öztürk and A. Ulubelen, “A new flavone from antioxidant extracts of Pistacia terebinthus,” Food Chemistry, vol. 103, no. 3, pp. 816-822, 2006.
  • [27] M.Z. Durak ve G. Uçak, “Solvent optimization and characterization of fatty acid profile and antimicrobial and antioxidant activities of Turkish Pistacia terebinthus L. Extracts,” Turkish Journal of Agriculture and Forestry, vol. 39, no. 1, pp. 10-19, 2015.
  • [28] H. Zhang, H.J. Forman ve J. Choi, “γ‐Glutamyl transpeptidase in glutathione biosynthesis,” Methods in Enzymology, vol. 401, pp. 468-483, 2005.
  • [29] S. Gezici and N. Sekeroglu, “Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents,” Anticancer Agents in Medicinal Chemistry, vol. 19, no. 1, pp. 101-111, 2019.
  • [30] C. Ding, W. Zhang, J. Li, J. Lei and J. Yu, “Cytotoxic constituents of ethyl acetate fraction from Dianthus superbus,” Natural Product Research, vol. 27, no. 18, pp. 1691-1694, 2013.

Antioxidative and Anticarcinogenic Effects of Terebinth (Pistacia terebinthus L) Extract on Hepatocellular Carcinoma Cells

Yıl 2023, Cilt: 11 Sayı: 3, 1517 - 1528, 31.07.2023

Güllü Kaymak Meliha Koldemir Gündüz Ertan Kanbur

https://doi.org/10.29130/dubited.1162385

Öz

In recent years, cancer research; It is one of the most important health problems of our age with its high mortality rate and incidence. In addition to existing treatment systems, it is vital to develop effective treatment strategies for the prevention of increasing cancer cases. Extracts from plants, essential oils, and bioactive components; Due to their natural origin, they have the potential to provide effective treatment with fewer side effects. The aim of this study was to examine the oxidative stress, cytotoxic and apoptotic effects of the extract of terebinth in hepatocellular carcinoma cells (HepG2). The results obtained with healthy liver epithelial cells (ZFL) were compared and it was evaluated whether this extract was specific to cancer cells. In our study, which was conducted for the first time in the literature, the iCELLigence system was used to determine the IC50 dose and duration of the extract obtained from terebinth by the soxhlet method, the MTT method to determine the cytotoxicity, and the Annexin V method to determine the apoptosis profile. In determining oxidative damage caused by terebinth extract; TAS, TOS, GSH, and lipid peroxidation levels and NADP-IDH, catalase, alkaline phosphatase, and acid phosphatase enzyme activities were analyzed by spectrophotometric methods. As a result of the analysis with the iCELLigence system, the 48-hour IC50 dose of terebinth extract in HepG2 cells was found to be 419 µg/mL. By cytotoxicity analysis, it was observed that the terebinth extract was more lethal in HepG2 cells compared to ZFL cells. Likewise, it was observed that the number of apoptotic and dead cells observed in HepG2 cells at 6 hours was higher than in ZFL cells. While the results observed in ZFL cells were not statistically significant in the analyzes performed to determine oxidative damage, significant oxidative damage was observed in HepG2 cells compared to both the control group and ZFL cells. The findings will be a source for studies on the development of new agents in cancer treatment.

Anahtar Kelimeler

Cancer liver cytotoxicity apoptosis oxidative stress terebinth.

Proje Numarası

TSA-2020-46 numaralı proje

Kaynakça

  • [1] I.T. Agar, N. Kaska and S. Kafkas, “Characterization of lipids in Pistacia species grown in Turkey,” In Acta Horticulturae, pp. 417-422, 1995.
  • [2] E. Ayrancı and A.C. Dalgıç, “Preparation of protein isolates from Pistacia terebinthus L. and examination of some functional properties,” Lebensmittel Wissenschaft Und Technologie, vol. 25, no. 5, pp. 442-444, 1992a.
  • [3] E. Ayrancı and A.C. Dalgıç, “Moisture sorption isotherms of Pistacia terebinthus L. and protein isolate,” Lebensmittel Wissenschaft Und Technologie, vol. 25, no. 5, pp. 482-483, 1992b.
  • [4] L. Bonsignore, F. Cottiglia and G. Loy, “Antibacterial activity of Pistacia lentiscus L. aerial parts,” Fitoterapia, vol. 69, no. 6, pp. 537-538, 1998.
  • [5] T. Baytop, Türkiye' deki Tıbbi Bitkiler İle Terapi, Birinci Baskı, İstanbul, Nobel Tıp Kitabevleri, 1999, 12. Bölüm, 111-117.
  • [6] E. Yeşilada, G. Honda and E. Sezik, “Traditional medicine in Turkey V. Folk Medicine in The Inner Taurus Mountains,” Journal of Ethnopharmacology, vol. 46, pp. 133-155, 1995.
  • [7] M. Couladis, M. Özcan, O. Tzakou and A. Akgül, “Comparative essential oil composition of various parts of the turpentine tree (Pistacia terebinthus L.) growing wild in Turkey,” Journal of the Science of Food and Agriculture, vol. 83, pp. 136-138, 2003.
  • [8] M.M. Özcan, O. Tzakou and M. Couladis, “Essential oil composition of the turpentine tree (Pistacia terebinthus L.) fruits growing wild in Turkey,” Food Chemistry, vol. 114, no. 1, pp 282-285, 2009.
  • [9] L. Dalgiç, S.O. Sermet ve G. Özkan, “Farklı kavurma sıcaklıklarının menengiç yağ kalite parametreleri üzerine etkisi,” Akademik Gıda, c. 9, s. 3, ss. 26-36, 2011.
  • [10] E.M. Giner-Larza, S. Ma´nez, M.C. Recio, R.M. Giner, J.M. Prieto and M. Cerda´-Nicola´s, “Oleanolic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity,” Eur. J. Pharmacol, vol. 428, pp. 137-143, 2001.
  • [11] T. Bakirel, S. Sener, U. Bakirel, O. Keles, G. Sennazli and A. Gurel, “The investigation of the effects of P. terebinthus L. upon experimentally induced hypercholesterolemia and atherosclerosis in rabbits,” Turkish Journal of Veterinary Sciences, vol. 27, pp. 1283-1292, 2003.
  • [12] F. Tetik, S. Civelek and U. Cakilcioglu, “Traditional Uses of Some Medicinal Plants in Malatya (Turkey),” Journal of Ethnopharmacology, vol. 146, no. 1, pp. 331-346, 2013.
  • [13] K. Canli, A. Yetgin, I. Akata and E.M. Altuner, “Antimicrobial Activity and Chemical Composition Screening of Epilobium montanum Root,” Indian Journal of Pharmaceutical Education and Research, vol. 51, no. 3, pp. 239-243, 2017.
  • [14] M.E. Bozyel, M. Şenturan, A. Benek, E. Merdamert Bozyel, K. Canli and E.M Altuner, “In Vitro Antimicrobial Activity Screening of Heliotropium europaeum Against Wide Range of Microorganisms and Multi Drug Resistant (Mdr) Bacteria,” European Journal of Biomedical and Pharmaceutical Sciences, vol. 6, no. 3, pp. 113-117, 2019.
  • [15] H.B. El‐Serag, “Epidemiology of hepatocellular carcinoma,” The Liver: Biology and Pathobiology, pp. 758-772, 2020.
  • [16] A. Yerlikaya, E. Erdoğan, E. Okur, Ş. Yerlikaya and B. Savran, “A novel combination treatment for breast cancer cells involving BAPTA-AM and proteasome inhibitor bortezomib,” Oncology Letters, vol. 12, no. 1, pp. 323-330, 2016.
  • [17] O. Erel, “A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation,” Clinical biochemistry, vol. 37, no. 4, pp. 277-285, 2004.
  • [18] O. Erel, “A new automated colorimetric method for measuring total oxidant status,” Clinical Biochemistry, vol. 38, no. 12, pp. 1103-1111, 2005.
  • [19] M. Koldemir Gündüz, “BGM a Newly Synthesised Boron Compound, Induces Apoptosis and Reduces Oxidative Stress by Inhibiting Lipogenesis in 3T3-L1 Adipocytes via PPARγ and CTRP3,” Biol Trace Elem Res, 2022, in press.
  • [20] H. Aebi, “Catalase Invitro. In: Methods of Enzymatic Analysis,” Ed: Bergmeyer HU, FL, 2nd ed, pp. 121- 126, 1974.
  • [21] K. Walter and C. Schutt, “Acid and alkaline phosphatase in serum,” Methods of Enzymatic Analysis, vol. 2, pp. 856-860, 1974.
  • [22] A. Ledwozyw, D. Michalak, A. Stepien and A. Kadziolka, “The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis,” Clin Chim Acta, vol. 155, no. 3, pp. 275-283, 1986.
  • [23] E. Beutler, “Glutathione in red cell metabolism: a manual of biochemical methods”, 2nd ed., Grune and Stratton, NY, pp. 112-114, 1975.
  • [24] Z. Selamoğlu, “Polyphenolic Compounds in Human Health with Pharmacological Properties”, Journal of Traditional Medicine Clinical Naturopathy, vol. 6, no. 4, pp.137, 2017.
  • [25] Z. Selamoğlu, “Biotechnological Approaches on Anticancer Activity of Flavonoids”, Modern Approaches in Drug Designing, vol. 1, no. 2, pp. 510, 2017.
  • [26] G. Topçu, M. Ay, A. Bilici, C. Sarıkürkçü, M. Öztürk and A. Ulubelen, “A new flavone from antioxidant extracts of Pistacia terebinthus,” Food Chemistry, vol. 103, no. 3, pp. 816-822, 2006.
  • [27] M.Z. Durak ve G. Uçak, “Solvent optimization and characterization of fatty acid profile and antimicrobial and antioxidant activities of Turkish Pistacia terebinthus L. Extracts,” Turkish Journal of Agriculture and Forestry, vol. 39, no. 1, pp. 10-19, 2015.
  • [28] H. Zhang, H.J. Forman ve J. Choi, “γ‐Glutamyl transpeptidase in glutathione biosynthesis,” Methods in Enzymology, vol. 401, pp. 468-483, 2005.
  • [29] S. Gezici and N. Sekeroglu, “Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents,” Anticancer Agents in Medicinal Chemistry, vol. 19, no. 1, pp. 101-111, 2019.
  • [30] C. Ding, W. Zhang, J. Li, J. Lei and J. Yu, “Cytotoxic constituents of ethyl acetate fraction from Dianthus superbus,” Natural Product Research, vol. 27, no. 18, pp. 1691-1694, 2013.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Güllü Kaymak 0000-0001-6309-0208

Meliha Koldemir Gündüz 0000-0003-0969-6377

Ertan Kanbur 0000-0001-8399-8942

Proje Numarası TSA-2020-46 numaralı proje
Yayımlanma Tarihi 31 Temmuz 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 11 Sayı: 3

Kaynak Göster

APA Kaymak, G., Koldemir Gündüz, M., & Kanbur, E. (2023). Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri. Düzce Üniversitesi Bilim Ve Teknoloji Dergisi, 11(3), 1517-1528. https://doi.org/10.29130/dubited.1162385
AMA Kaymak G, Koldemir Gündüz M, Kanbur E. Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri. DÜBİTED. Temmuz 2023;11(3):1517-1528. doi:10.29130/dubited.1162385
Chicago Kaymak, Güllü, Meliha Koldemir Gündüz, ve Ertan Kanbur. “Menengiç (Pistacia Terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif Ve Antikarsinojenik Etkileri”. Düzce Üniversitesi Bilim Ve Teknoloji Dergisi 11, sy. 3 (Temmuz 2023): 1517-28. https://doi.org/10.29130/dubited.1162385.
EndNote Kaymak G, Koldemir Gündüz M, Kanbur E (01 Temmuz 2023) Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri. Düzce Üniversitesi Bilim ve Teknoloji Dergisi 11 3 1517–1528.
IEEE G. Kaymak, M. Koldemir Gündüz, ve E. Kanbur, “Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri”, DÜBİTED, c. 11, sy. 3, ss. 1517–1528, 2023, doi: 10.29130/dubited.1162385.
ISNAD Kaymak, Güllü vd. “Menengiç (Pistacia Terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif Ve Antikarsinojenik Etkileri”. Düzce Üniversitesi Bilim ve Teknoloji Dergisi 11/3 (Temmuz 2023), 1517-1528. https://doi.org/10.29130/dubited.1162385.
JAMA Kaymak G, Koldemir Gündüz M, Kanbur E. Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri. DÜBİTED. 2023;11:1517–1528.
MLA Kaymak, Güllü vd. “Menengiç (Pistacia Terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif Ve Antikarsinojenik Etkileri”. Düzce Üniversitesi Bilim Ve Teknoloji Dergisi, c. 11, sy. 3, 2023, ss. 1517-28, doi:10.29130/dubited.1162385.
Vancouver Kaymak G, Koldemir Gündüz M, Kanbur E. Menengiç (Pistacia terebinthus L) Ekstraktının Hepatoselüler Karsinom Hücrelerinde Antioksidatif ve Antikarsinojenik Etkileri. DÜBİTED. 2023;11(3):1517-28.
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