Araştırma Makalesi
BibTex RIS Kaynak Göster

ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS

Yıl 2023, Cilt: 47 Sayı: 3, 836 - 844, 20.09.2023

Ali Ergüç Ege Arzuk Gökay Albayrak Fuat Karakuş Hayati Okur Şüra Baykan

https://doi.org/10.33483/jfpau.1312637

Öz

Objective: The first goal of the present study is to investigate the role of mitochondria due to the Crabtree effect in HepG2 cells exposed to ISO in either glucose- or galactose-conditioned media. The second aim is to predict the interactions between electron transport chain (ETC) complexes and ISO, which might be the possible reason for mitochondrial dysfunction.
Material and Method: Cell viability and membrane damage for HepG2 cells exposed to ISO (12.5, 25, 50, 100, and 250 µM) were assessed by MTT and LDH leakage assays in either glucose- or galactose-conditioned media. The affinity of ISO to ETC complexes was also determined by a molecular docking study.
Result and Discussion: MTT assay showed that 250 µM ISO leads to cytotoxic activity in glucose-conditioned media, while 25 µM and higher concentrations of ISO decrease cell viability in galactose-conditioned media. A membrane damage assay conducted in a glucose-conditioned media assay revealed that 250 µM ISO disrupts the cell membrane. 100 and 250 µM ISO increased membrane damage in galactose-conditioned media. According to docking simulations, binding affinities of ISO to ETC complexes are in descending order: Complex IV > Complex I > Complex III > Complex II. Inhibition of complex IV by ISO inhibits the transfer of electrons from cytochrome c to oxygen, and the proton gradient collapses. The present study proposed that ISO leads to mitochondrial dysfunction via inhibition of the ETC.

Anahtar Kelimeler

Anticancer crabtree effect electron transport chain isoimperatorin mitochondrial dysfunction

Teşekkür

We gratefully thank Prof. Ayşe NALBANTSOY (Bioengineering Department, Ege University) for the laboratory facilities.

Kaynakça

  • 1. 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: A Cancer Journal for Clinicians, 71(3), 209-249. [CrossRef]
  • 2. Zugazagoitia, J., Guedes, C., Ponce, S., Ferrer, I., Molina-Pinelo, S., Paz-Ares, L. (2016). Current challenges in cancer treatment. Clinical Therapeutics, 38(7), 1551-1566. [CrossRef]
  • 3. Tsimberidou, A.M., Fountzilas, E., Nikanjam, M., Kurzrock, R. (2020). Review of precision cancer medicine: Evolution of the treatment paradigm. Cancer Treatment Reviews, 86, 102019. [CrossRef]
  • 4. Liberti, M.V., Locasale, J.W. (2016). The warburg effect: How does it benefit cancer cells? Trends in Biochemical Sciences, 41(3), 211-218. [CrossRef]
  • 5. Marroquin, L.D., Hynes, J., Dykens, J.A., Jamieson, J.D., Will, Y. (2007). Circumventing the crabtree effect: Replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicological sciences: An Official Journal of the Society of Toxicology, 97(2), 539-547. [CrossRef]
  • 6. Pereira, C.V., Oliveira, P.J., Will, Y., Nadanaciva, S. (2012). Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms. Toxicology and Applied Pharmacology, 264(2), 167-181. [CrossRef]
  • 7. Swiss, R., Will, Y. (2011). Assessment of mitochondrial toxicity in HepG2 cells cultured in high-glucose- or galactose-containing media. Current Protocols in Toxicology, Chapter 2, Unit2.20. [CrossRef]
  • 8. Will, Y., Dykens, J. (2014). Mitochondrial toxicity assessment in industry-A decade of technology development and insight. Expert Opinion on Drug Metabolism & Toxicology, 10(8), 1061-1067. [CrossRef]
  • 9. Dott, W., Mistry, P., Wright, J., Cain, K., Herbert, K.E. (2014). Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity. Redox Biology, 2, 224-233. [CrossRef]
  • 10. Liu, Y., Shi, Y. (2020). Mitochondria as a target in cancer treatment. MedComm, 1(2), 129-139. [CrossRef]
  • 11. González-Vallinas, M., González-Castejón, M., Rodríguez-Casado, A., Ramírez de Molina, A. (2013). Dietary phytochemicals in cancer prevention and therapy: A complementary approach with promising perspectives. Nutrition Reviews, 71(9), 585-599. [CrossRef]
  • 12. Wong, S.C., Kamarudin, M.N.A., Naidu, R. (2021). Anticancer mechanism of curcumin on human glioblastoma. Nutrients, 13(3), 950. [CrossRef]
  • 13. Danchul, T.Y., Kuznetsova, G., Sokolova, E., Kuz’mina, L. (1979). Coumarins from the roots of Prangos lamellata. Chemistry of Natural Compounds 15, 753.
  • 14. Kuznetsova, G., Danchul. T.Y., Sokolova, E., Kuz'mina, L. (1979b). Coumarins from the roots of Prangos arcis-romanae Chemistry of Natural Compounds, 15, 751-752.
  • 15. Wei, Y., Ito, Y. (2006). Preparative isolation of imperatorin, oxypeucedanin and isoimperatorin from traditional Chinese herb "bai zhi" Angelica dahurica (Fisch.ex Hoffm) Benth. et Hook using multidimensional high-speed counter-current chromatography. Journal of Chromatography. A, 1115(1-2), 112-117. [CrossRef]
  • 16. Baek, N.I., Ahn, E.M., Kim, H.Y., Park, Y.D. (2000). Furanocoumarins from the root of Angelica dahurica. Archives of Pharmacal Research, 23(5), 467-470. [CrossRef]
  • 17. Bruni, R., Barreca, D., Protti, M., Brighenti, V., Righetti, L., Anceschi, L., Mercolini, L., Benvenuti, S., Gattuso, G., Pellati, F. (2019). Botanical sources, chemistry, analysis, and biological activity of furanocoumarins of pharmaceutical interest. Molecules, 24(11), 2163. [CrossRef]
  • 18. Moon, T.C., Jin, M., Son, J.K., Chang, H.W. (2008). The effects of isoimperatorin isolated from Angelicae dahuricae on cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells. Archives of Pharmacal Research, 31(2), 210-215. [CrossRef]
  • 19. Park, H.Y., Kwon, S.B., Heo, N.K., Chun, W.J., Kim, M.J., Kwon, Y.S. (2011). Constituents of the stem of Angelica gigas with rat lens aldose reductase inhibitory activity. Journal of the Korean Society for Applied Biological Chemistry, 54(2), 194-199. [CrossRef]
  • 20. Kim, Y.K., Kim, Y.S., Ryu, S.Y. (2007). Antiproliferative effect of furanocoumarins from the root of Angelica dahurica on cultured human tumor cell lines. Phytotherapy Research, 21(3), 288-290. [CrossRef]
  • 21. Tong, K., Xin, C., Chen, W. (2017). Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway. Oncology Letters, 13(1), 518-524. [CrossRef]
  • 22. Albayrak, G. (2020). PhD Thesis. Investigation on phytochemistry and bioactivity of endemic Prangos heyniae H. Duman & M.F. watson and Prangos uechtritzii Boiss. & Hausskn. Species naturally distributed in Anatolia. Department of Pharmaceutical Botany, Faculty of Pharmacy, Ege University, İzmir, Turkey.
  • 23. Albayrak, G., Demir, S., Koyu, H., Baykan, S. (2023). Anticholinesterase and antityrosinase activities of endemic Prangos heyniae H. Duman & M.F. Watson and its metabolites. İstanbul Journal of Pharmacy, 53 (1), 51-57. [CrossRef]
  • 24. Kuzu, B., Ergüç, A., Karakuş, F., Arzuk, E. (2023). Design, synthesis, and antiproliferative activities of novel thiazolyl-pyrazole hybrid derivatives. Medicinal Chemistry Research, in press. [CrossRef]
  • 25. Adan, A., Kiraz, Y., Baran, Y. (2016). Cell proliferation and cytotoxicity assays. Current Pharmaceutical Biotechnology, 17(14), 1213-1221. [CrossRef]
  • 26. Hassoun, E.A., Roche, V.F., Stohs, S.J. (1993). Release of enzymes by ricin from macrophages and Chinese hamster ovary cells in culture. Toxicology Methods, 3(2), 119-129. [CrossRef]
  • 27. Desler, C., Munch-Petersen, B., Stevnsner, T., Matsui, S., Kulawiec, M., Singh, K.K., Rasmussen, L.J. (2007). Mitochondria as determinant of nucleotide pools and chromosomal stability. Mutation Research, 625(1-2), 112-124. [CrossRef]
  • 28. Kamalian, L., Chadwick, A.E., Bayliss, M., French, N.S., Monshouwer, M., Snoeys, J., Park, B.K. (2015). The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death. Toxicology in Vitro, 29(4), 732-740. [CrossRef]
  • 29. Vaupel, P., Schmidberger, H., Mayer, A. (2019). The warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression. International Journal of Radiation Biology, 95(7), 912-919. [CrossRef]
  • 30. Shokoohinia, Y., Sajjadi, S.E., Gholamzadeh, S., Fattahi, A., Behbahani, M. (2014). Antiviral and cytotoxic evaluation of coumarins from Prangos ferulacea. Pharmaceutical Biology, 52(12), 1543-1549. [CrossRef]
  • 31. Bruno, M., Ilardi, V., Lupidi, G., Quassinti, L., Bramucci, M., Fiorini, D., Venditti, A., Maggi, F. (2019). The nonvolatile and volatile metabolites of prangos ferulacea and their biological properties. Planta Medica, 85(11-12), 815-824. [CrossRef]
  • 32. Yang X., Liang L., Wang X. (2018). Protective effects of isoimperatorin on CCL4 induced acute liver injury in mice. Chinese Journal of Hospital Pharmacy, 38(13), 19-23.
  • 33. Nolfi-Donegan, D., Braganza, A., Shiva, S. (2020). Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement. Redox Biology, 37, 101674. [CrossRef]
  • 34. Kühlbrandt, W. (2015). Structure and function of mitochondrial membrane protein complexes. BMC Biology, 13, 89. [CrossRef]

İZOİMPERATORİN ARACILIKLI ANTİKANSER AKTİVİTE: MİTOKONDRİYAL DİSFONKSİYONUN HEPG2 HÜCRELERİNDEKİ ROLÜ

Yıl 2023, Cilt: 47 Sayı: 3, 836 - 844, 20.09.2023

Ali Ergüç Ege Arzuk Gökay Albayrak Fuat Karakuş Hayati Okur Şüra Baykan

https://doi.org/10.33483/jfpau.1312637

Öz

Amaç: Çalışma kapsamındaki ilk amaç, glukoz veya galaktoz içeren besiyerlerinde İzoimperatorin’e (İZO) maruz kalmış HepG2 hücrelerindeki mitokondrinin rolünü Crabtree etkisi nedeni ile araştırmaktır. İkinci amaç, mitokondriyal disfonksiyonun ortaya çıkmasında rolü olabilecek olan İZO ve elektron transfer zinciri arasındaki (ETZ) etkileşimi öngörmektir.
Gereç ve Yöntem: Glukoz veya galaktoz içeren besiyerlerinde İZO (12.5, 25, 50, 100 ve 250 µM) ile inkübe edilen HepG2 hücrelerin canlılığı ve membran hasarı MTT ve LDH sızma deneyleri ile gerçekleştirilmiştir. İZO‘nun ETZ kompleksleri üzerine olan afinitesi moleküler kenetleme çalışması ile analiz edilmiştir.
Sonuç ve Tartışma: MTT deneyi sonuçlarına göre glukoz içeren besiyerinde 250 µM İZO sitotoksik etki gösterirken, galaktoz içeren besiyerinde 25 µM ve daha yüksek konsantrasyonlar hücre canlılığını azaltmıştır. Glukoz içeren besiyerinde gerçekleştirilen membran hasarı deneyi, 250 uM İZO’nun membran bütünlüğünü bozduğunu göstermiştir. Galaktoz içeren besiyerinde 100 ve 250 uM İSO membran hasarını artırmıştır. Moleküler kenetlenme çalışma sonuçlarına göre İZO’nun ETZ komplekleri üzerine olan afinitesi Kompleks IV > Kompleks I > Kompleks III > Kompleks II şeklindedir. İZO, elektronun sitokrom C’den oksijene aktarılmasını engelleyerek kompleks IV’ün inhibisyonunu yapmakta ve proton gradiyentinin azalmasına neden olmaktadır. Elde edilen sonuçlar, İZO’nun gerçekleştirdiği ETZ inhibisyonunun mitokondriyal disfonksiyona neden olabileceğini göstermektedir.

Anahtar Kelimeler

Antikanser crabtree etkisi elektron transfer zinciri izoimperatorin mitokondriyal disfonksiyon

Kaynakça

  • 1. 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: A Cancer Journal for Clinicians, 71(3), 209-249. [CrossRef]
  • 2. Zugazagoitia, J., Guedes, C., Ponce, S., Ferrer, I., Molina-Pinelo, S., Paz-Ares, L. (2016). Current challenges in cancer treatment. Clinical Therapeutics, 38(7), 1551-1566. [CrossRef]
  • 3. Tsimberidou, A.M., Fountzilas, E., Nikanjam, M., Kurzrock, R. (2020). Review of precision cancer medicine: Evolution of the treatment paradigm. Cancer Treatment Reviews, 86, 102019. [CrossRef]
  • 4. Liberti, M.V., Locasale, J.W. (2016). The warburg effect: How does it benefit cancer cells? Trends in Biochemical Sciences, 41(3), 211-218. [CrossRef]
  • 5. Marroquin, L.D., Hynes, J., Dykens, J.A., Jamieson, J.D., Will, Y. (2007). Circumventing the crabtree effect: Replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicological sciences: An Official Journal of the Society of Toxicology, 97(2), 539-547. [CrossRef]
  • 6. Pereira, C.V., Oliveira, P.J., Will, Y., Nadanaciva, S. (2012). Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms. Toxicology and Applied Pharmacology, 264(2), 167-181. [CrossRef]
  • 7. Swiss, R., Will, Y. (2011). Assessment of mitochondrial toxicity in HepG2 cells cultured in high-glucose- or galactose-containing media. Current Protocols in Toxicology, Chapter 2, Unit2.20. [CrossRef]
  • 8. Will, Y., Dykens, J. (2014). Mitochondrial toxicity assessment in industry-A decade of technology development and insight. Expert Opinion on Drug Metabolism & Toxicology, 10(8), 1061-1067. [CrossRef]
  • 9. Dott, W., Mistry, P., Wright, J., Cain, K., Herbert, K.E. (2014). Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity. Redox Biology, 2, 224-233. [CrossRef]
  • 10. Liu, Y., Shi, Y. (2020). Mitochondria as a target in cancer treatment. MedComm, 1(2), 129-139. [CrossRef]
  • 11. González-Vallinas, M., González-Castejón, M., Rodríguez-Casado, A., Ramírez de Molina, A. (2013). Dietary phytochemicals in cancer prevention and therapy: A complementary approach with promising perspectives. Nutrition Reviews, 71(9), 585-599. [CrossRef]
  • 12. Wong, S.C., Kamarudin, M.N.A., Naidu, R. (2021). Anticancer mechanism of curcumin on human glioblastoma. Nutrients, 13(3), 950. [CrossRef]
  • 13. Danchul, T.Y., Kuznetsova, G., Sokolova, E., Kuz’mina, L. (1979). Coumarins from the roots of Prangos lamellata. Chemistry of Natural Compounds 15, 753.
  • 14. Kuznetsova, G., Danchul. T.Y., Sokolova, E., Kuz'mina, L. (1979b). Coumarins from the roots of Prangos arcis-romanae Chemistry of Natural Compounds, 15, 751-752.
  • 15. Wei, Y., Ito, Y. (2006). Preparative isolation of imperatorin, oxypeucedanin and isoimperatorin from traditional Chinese herb "bai zhi" Angelica dahurica (Fisch.ex Hoffm) Benth. et Hook using multidimensional high-speed counter-current chromatography. Journal of Chromatography. A, 1115(1-2), 112-117. [CrossRef]
  • 16. Baek, N.I., Ahn, E.M., Kim, H.Y., Park, Y.D. (2000). Furanocoumarins from the root of Angelica dahurica. Archives of Pharmacal Research, 23(5), 467-470. [CrossRef]
  • 17. Bruni, R., Barreca, D., Protti, M., Brighenti, V., Righetti, L., Anceschi, L., Mercolini, L., Benvenuti, S., Gattuso, G., Pellati, F. (2019). Botanical sources, chemistry, analysis, and biological activity of furanocoumarins of pharmaceutical interest. Molecules, 24(11), 2163. [CrossRef]
  • 18. Moon, T.C., Jin, M., Son, J.K., Chang, H.W. (2008). The effects of isoimperatorin isolated from Angelicae dahuricae on cyclooxygenase-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells. Archives of Pharmacal Research, 31(2), 210-215. [CrossRef]
  • 19. Park, H.Y., Kwon, S.B., Heo, N.K., Chun, W.J., Kim, M.J., Kwon, Y.S. (2011). Constituents of the stem of Angelica gigas with rat lens aldose reductase inhibitory activity. Journal of the Korean Society for Applied Biological Chemistry, 54(2), 194-199. [CrossRef]
  • 20. Kim, Y.K., Kim, Y.S., Ryu, S.Y. (2007). Antiproliferative effect of furanocoumarins from the root of Angelica dahurica on cultured human tumor cell lines. Phytotherapy Research, 21(3), 288-290. [CrossRef]
  • 21. Tong, K., Xin, C., Chen, W. (2017). Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway. Oncology Letters, 13(1), 518-524. [CrossRef]
  • 22. Albayrak, G. (2020). PhD Thesis. Investigation on phytochemistry and bioactivity of endemic Prangos heyniae H. Duman & M.F. watson and Prangos uechtritzii Boiss. & Hausskn. Species naturally distributed in Anatolia. Department of Pharmaceutical Botany, Faculty of Pharmacy, Ege University, İzmir, Turkey.
  • 23. Albayrak, G., Demir, S., Koyu, H., Baykan, S. (2023). Anticholinesterase and antityrosinase activities of endemic Prangos heyniae H. Duman & M.F. Watson and its metabolites. İstanbul Journal of Pharmacy, 53 (1), 51-57. [CrossRef]
  • 24. Kuzu, B., Ergüç, A., Karakuş, F., Arzuk, E. (2023). Design, synthesis, and antiproliferative activities of novel thiazolyl-pyrazole hybrid derivatives. Medicinal Chemistry Research, in press. [CrossRef]
  • 25. Adan, A., Kiraz, Y., Baran, Y. (2016). Cell proliferation and cytotoxicity assays. Current Pharmaceutical Biotechnology, 17(14), 1213-1221. [CrossRef]
  • 26. Hassoun, E.A., Roche, V.F., Stohs, S.J. (1993). Release of enzymes by ricin from macrophages and Chinese hamster ovary cells in culture. Toxicology Methods, 3(2), 119-129. [CrossRef]
  • 27. Desler, C., Munch-Petersen, B., Stevnsner, T., Matsui, S., Kulawiec, M., Singh, K.K., Rasmussen, L.J. (2007). Mitochondria as determinant of nucleotide pools and chromosomal stability. Mutation Research, 625(1-2), 112-124. [CrossRef]
  • 28. Kamalian, L., Chadwick, A.E., Bayliss, M., French, N.S., Monshouwer, M., Snoeys, J., Park, B.K. (2015). The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death. Toxicology in Vitro, 29(4), 732-740. [CrossRef]
  • 29. Vaupel, P., Schmidberger, H., Mayer, A. (2019). The warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression. International Journal of Radiation Biology, 95(7), 912-919. [CrossRef]
  • 30. Shokoohinia, Y., Sajjadi, S.E., Gholamzadeh, S., Fattahi, A., Behbahani, M. (2014). Antiviral and cytotoxic evaluation of coumarins from Prangos ferulacea. Pharmaceutical Biology, 52(12), 1543-1549. [CrossRef]
  • 31. Bruno, M., Ilardi, V., Lupidi, G., Quassinti, L., Bramucci, M., Fiorini, D., Venditti, A., Maggi, F. (2019). The nonvolatile and volatile metabolites of prangos ferulacea and their biological properties. Planta Medica, 85(11-12), 815-824. [CrossRef]
  • 32. Yang X., Liang L., Wang X. (2018). Protective effects of isoimperatorin on CCL4 induced acute liver injury in mice. Chinese Journal of Hospital Pharmacy, 38(13), 19-23.
  • 33. Nolfi-Donegan, D., Braganza, A., Shiva, S. (2020). Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement. Redox Biology, 37, 101674. [CrossRef]
  • 34. Kühlbrandt, W. (2015). Structure and function of mitochondrial membrane protein complexes. BMC Biology, 13, 89. [CrossRef]
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Toksikoloji
Bölüm Araştırma Makalesi
Yazarlar

Ali Ergüç 0000-0002-9791-4399

Ege Arzuk 0000-0002-3239-4855

Gökay Albayrak 0000-0002-5729-0796

Fuat Karakuş 0000-0002-5260-3650

Hayati Okur 0000-0001-6807-8208

Şüra Baykan 0000-0002-3624-4811

Erken Görünüm Tarihi 24 Temmuz 2023
Yayımlanma Tarihi 20 Eylül 2023
Gönderilme Tarihi 11 Haziran 2023
Kabul Tarihi 20 Temmuz 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 47 Sayı: 3

Kaynak Göster

APA Ergüç, A., Arzuk, E., Albayrak, G., Karakuş, F., vd. (2023). ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS. Journal of Faculty of Pharmacy of Ankara University, 47(3), 836-844. https://doi.org/10.33483/jfpau.1312637
AMA Ergüç A, Arzuk E, Albayrak G, Karakuş F, Okur H, Baykan Ş. ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS. Ankara Ecz. Fak. Derg. Eylül 2023;47(3):836-844. doi:10.33483/jfpau.1312637
Chicago Ergüç, Ali, Ege Arzuk, Gökay Albayrak, Fuat Karakuş, Hayati Okur, ve Şüra Baykan. “ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS”. Journal of Faculty of Pharmacy of Ankara University 47, sy. 3 (Eylül 2023): 836-44. https://doi.org/10.33483/jfpau.1312637.
EndNote Ergüç A, Arzuk E, Albayrak G, Karakuş F, Okur H, Baykan Ş (01 Eylül 2023) ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS. Journal of Faculty of Pharmacy of Ankara University 47 3 836–844.
IEEE A. Ergüç, E. Arzuk, G. Albayrak, F. Karakuş, H. Okur, ve Ş. Baykan, “ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS”, Ankara Ecz. Fak. Derg., c. 47, sy. 3, ss. 836–844, 2023, doi: 10.33483/jfpau.1312637.
ISNAD Ergüç, Ali vd. “ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS”. Journal of Faculty of Pharmacy of Ankara University 47/3 (Eylül 2023), 836-844. https://doi.org/10.33483/jfpau.1312637.
JAMA Ergüç A, Arzuk E, Albayrak G, Karakuş F, Okur H, Baykan Ş. ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS. Ankara Ecz. Fak. Derg. 2023;47:836–844.
MLA Ergüç, Ali vd. “ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS”. Journal of Faculty of Pharmacy of Ankara University, c. 47, sy. 3, 2023, ss. 836-44, doi:10.33483/jfpau.1312637.
Vancouver Ergüç A, Arzuk E, Albayrak G, Karakuş F, Okur H, Baykan Ş. ISOIMPERATORIN-MEDIATED ANTICANCER ACTIVITY: ROLE OF MITOCHONDRIAL DYSFUNCTION IN HEPG2 CELLS. Ankara Ecz. Fak. Derg. 2023;47(3):836-44.
 Kapak Resmi İndir

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.