TY  - JOUR
T1  - In silico and in vitro evaluation of oxypeucedanin-induced anticancer activity: Mitotoxicity?
TT  - Oksipösedanin kaynaklı antikanser aktivitenin in siliko ve in vitro değerlendirilmesi: Mitotoksisite?
AU  - Ergüç, Ali
AU  - Okur, Hayati
AU  - Karakuş, Fuat
AU  - Albayrak, Gökay
AU  - Arzuk, Ege
AU  - Baykan, Şüra
PY  - 2023
DA  - December
Y2  - 2023
DO  - 10.30569/adiyamansaglik.1325975
JF  - Adıyaman Üniversitesi Sağlık Bilimleri Dergisi
JO  - ADYÜ Sağlık Bilimleri Derg
PB  - Adıyaman University
WT  - DergiPark
SN  - 2458-9179
SP  - 153
EP  - 161
VL  - 9
IS  - 3
LA  - en
AB  - Aim: This study aims to evaluate the alterations in Oxypeucedanin (OXY)-mediated anticancer activity in different media. Second aim is to predict the affinity of OXY to electron transfer chain (ETC) complexes.Materials and Methods: MTT and LDH leakage assays were performed with OXY. Molecular docking studies were also conducted to predict the affinity of OXY to ETC complexes.Results: 250 µM OXY reduced viability in glucose media. ≥50 µM OXY decreased viability in galactose media. ≥50 µM OXY increased membrane disruption in galactose media. Molecular docking studies also showed that OXY might possess the capacity to bind to the inhibition sites of Complex I and IV.Conclusion: Galactose-conditioned media exacerbated the OXY-mediated cytotoxicity. Preliminary results suggested that mitotoxicity might take part in anticancer activity. Furthermore, OXY might cause ETC dysfunctions due to selective inhibition of Complex I and IV.
KW  - Oxypeucedanin
KW  - Mitotoxicity
KW  - Anticancer activity
KW  - In silico
N2  - Amaç: Çalışmanın amacı, farklı ortamlarda Oksipösedanin (OKS) aracılı antikanser aktivitedeki değişiklikleri değerlendirmektir. İkinci amaç, OKS’inin elektron transfer zincirine (ETZ) karşı afinitesini öngörmektir.Gereç ve Yöntem: MTT ve LDH sızma deneyleri OKS ile gerçekleştirilmiştir. Ayrıca, OKS’inin ETZ komplekslerine karşı afinitesini öngörmek için moleküler kenetlenme çalışmaları uygulanmıştır.Bulgular: Glukoz içeren ortamda 250 µM OKS canlılığı azaltmıştır. Galaktoz içeren ortamda ≥50 µM OKS hücre canlılığını azalmıştır. Galaktoz içeren ortamda ≥50 µM OKS membran parçalanmasını artırmıştır. Moleküler kenetlenme çalışmaları, OKS'inin Kompleks I ve IV'ün inhibisyon bölgelerine bağlanma kapasitesine sahip olabileceğini göstermektedir.Sonuç: Galaktoz içeren ortam, OKS aracılı sitotoksisiteyi artırmıştır. Ön sonuçlar, antikanser aktivitede mitotoksisitenin yer alabileceğini göstermektedir. Ayrıca OKS, Kompleks I ve IV'ün seçici inhibisyonu nedeni ile ETZ disfonksiyonuna neden olabilmektedir.
CR  - González-Vallinas M, González-Castejón M, Rodríguez-Casado A, Ramírez de Molina A. Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives. Nutrition Reviews. 2013;71(9):585-599. doi: 10.1111/nure.12051
CR  - Wong SC, Kamarudin MNA, Naidu R. Anticancer Mechanism of Curcumin on Human Glioblastoma. Nutrients. 2021;13(3):950. doi:10.3390/nu13030950
CR  - Mottaghipisheh J, Kiss T, Tóth B, Csupor D. The Prangos genus: a comprehensive review on traditional use, phytochemistry, and pharmacological activities. Phytochemistry Reviews. 2020;19(6):1449-1470. doi: 10.1007/s11101-020-09688-3
CR  - Mottaghipisheh J. Oxypeucedanin: Chemotaxonomy, Isolation, and Bioactivities. Plants (Basel). 2021;10(8):1577. doi:10.3390/plants10081577
CR  - Oh H, Lee HS, Kim T, et al. Furocoumarins from Angelica dahurica with hepatoprotective activity on tacrine-induced cytotoxicity in HepG2 cells. Planta Medica. 2002;68(5):463-464. doi:10.1055/s-2002-32075
CR  - Park SH, Hong JY, Park HJ, Lee SK. The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells. Molecules. 2020;25(3):501. doi:10.3390/molecules25030501
CR  - Pfeffer CM, Singh ATK. Apoptosis: A Target for Anticancer Therapy. International Journal of Molecular Sciences. 2018;19(2):448. doi:10.3390/ijms19020448
CR  - Liu Y, Shi Y. Mitochondria as a target in cancer treatment. MedComm. 2020;1(2):129-139. doi:10.1002/mco2.16
CR  - Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nature Reviews. Drug Discovery. 2010;9(6):447-464. doi:10.1038/nrd3137
CR  - Badrinath N, Yoo SY. Mitochondria in cancer: in the aspects of tumorigenesis and targeted therapy. Carcinogenesis. 2018;39(12):1419-1430. doi:10.1093/carcin/bgy148
CR  - Pereira CV, Oliveira PJ, Will Y, Nadanaciva S. Mitochondrial bioenergetics and drug-induced toxicity in a panel of mouse embryonic fibroblasts with mitochondrial DNA single nucleotide polymorphisms. Toxicology and Applied Pharmacology. 2012;264(2):167-181. doi:10.1016/j.taap.2012.07.030
CR  - Ong MM, Latchoumycandane C, Boelsterli UA. Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. Toxicological Sciences. 2007;97(1):205-213. doi:10.1093/toxsci/kfl180
CR  - Ramachandran A, Lebofsky M, Weinman SA, Jaeschke H. The impact of partial manganese superoxide dismutase (SOD2)-deficiency on mitochondrial oxidant stress, DNA fragmentation and liver injury during acetaminophen hepatotoxicity. Toxicology and Applied Pharmacology. 2011;251(3):226-233. doi:10.1016/j.taap.2011.01.004
CR  - Diaz-Ruiz R, Rigoulet M, Devin A. The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression. Biochimica et Biophysica Acta. 2011;1807(6):568-576. doi:10.1016/j.bbabio.2010.08.010
CR  - Pascale RM, Calvisi DF, Simile MM, Feo CF, Feo F. The Warburg Effect 97 Years after Its Discovery. Cancers (Basel). 2020;12(10):2819. doi:10.3390/cancers12102819
CR  - Marroquin LD, Hynes J, Dykens JA, Jamieson JD, Will Y. Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicological Sciences. 2007;97(2):539-547. doi:10.1093/toxsci/kfm052
CR  - Swiss R, Will Y. Assessment of mitochondrial toxicity in HepG2 cells cultured in high-glucose- or galactose-containing media. Current Protocols in Toxicology. 2011;49(1):2-20. doi:10.1002/0471140856.tx0220s49
CR  - Will Y, Dykens J. Mitochondrial toxicity assessment in industry-a decade of technology development and insight. Expert Opinion on Drug Metabolism Toxicology. 2014;10(8):1061-1067. doi:10.1517/17425255.2014.939628
CR  - Dott W, Mistry P, Wright J, Cain K, Herbert KE. Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity. Redox Biology. 2014;2:224-233. doi:10.1016/j.redox.2013.12.028
CR  - Tavakoli S, Delnavazi MR, Hadjiaghaee R, et al. Bioactive coumarins from the roots and fruits of Ferulago trifida Boiss., an endemic species to Iran. Natural Product Research. 2018;32(22):2724-2728. doi:10.1080/14786419.2017.1375915
CR  - Kim YK, Kim YS, Ryu SY. Antiproliferative effect of furanocoumarins from the root of Angelica dahurica on cultured human tumor cell lines. Phytotherapy Research. 2007;21(3):288-290. doi:10.1002/ptr.2043
CR  - Mottaghipisheh J, Nové M, Spengler G, Kúsz N, Hohmann J, Csupor D. Antiproliferative and cytotoxic activities of furocoumarins of Ducrosia anethifolia. Pharmaceutical Biology. 2018;56(1):658-664. doi:10.1080/13880209.2018.1548625
CR  - Albayrak G, Demir S, Kose FA, Baykan S. New coumarin glycosides from endemic Prangos heyniae H. Duman & M.F. Watson. Natural Product Research. 2023;37(2):227-239. doi:10.1080/14786419.2021.1961138
CR  - Kuzu B, Ergüç A, Karakuş F, Arzuk E. Design, synthesis, and antiproliferative activities of novel thiazolyl-pyrazole hybrid derivatives. Medicinal Chemistry Research. 2023;32:1690-1700. doi:10.1007/s00044-023-03090-2
CR  - Ergüç A, Karakuş F, Arzuk E, Mutlu N, Orhan H. Role of Oxidative Stress and Reactive Metabolites in Cytotoxicity & Mitotoxicity of Clozapine, Diclofenac and Nifedipine in CHO-K1 Cells In Vitro. Endocrine, Metabolic & Immune Disorders Drug Targets. 2023;(in press). doi: 10.2174/1871530323666230419084613
CR  - Guo R, Zong S, Wu M, Gu J, Yang M. Architecture of Human Mitochondrial Respiratory Megacomplex I2III2IV2. Cell. 2017;170(6):1247-1257. doi:10.1016/j.cell.2017.07.050
CR  - Du Z, Zhou X, Lai Y, et al. Structure of the human respiratory complex II. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(18). doi:10.1073/pnas.2216713120
CR  - Zong S, Wu M, Gu J, Liu T, Guo R, Yang M. Structure of the intact 14-subunit human cytochrome c oxidase. Cell Research. 2018;28(10):1026-1034. doi:10.1038/s41422-018-0071-1
CR  - Heinz S, Freyberger A, Lawrenz B, Schladt L, Schmuck G, Ellinger-Ziegelbauer H. Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation. Scientific Reports. 2017;7:45465. doi:10.1038/srep45465
CR  - Patra S, Pradhan B, Nayak R, et al. Apoptosis and autophagy modulating dietary phytochemicals in cancer therapeutics: Current evidences and future perspectives. Phytotherapy Research. 2021;35(8):4194-4214. doi:10.1002/ptr.7082
CR  - Sitarek P, Synowiec E, Kowalczyk T, et al. Anticancer Properties of Plectranthus ornatus-Derived Phytochemicals Inducing Apoptosis via Mitochondrial Pathway. International Journal of Molecular Sciences. 2022;23(19):11653. doi:10.3390/ijms231911653
CR  - Xiao J, Wang J, Yuan L, Hao L, Wang D. Study on the mechanism and intervention strategy of sunitinib induced nephrotoxicity. European Journal of Pharmacology. 2019;864:172709. doi:10.1016/j.ejphar.2019.172709
CR  - Jalilian F, Moieni-Arya M, Hosseinzadeh L, Shokoohinia Y. Oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl protect PC12 pheochromocytoma cells from oxidative stress and apoptosis induced by doxorubicin. Research in Pharmaceutical Sciences. 2021;17(1):12-21. doi:10.4103/1735-5362.329922
CR  - Jalilian F, Moieni-Arya M, Hosseinzadeh L, Shokoohinia Y. Oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl protect PC12 pheochromocytoma cells from oxidative stress and apoptosis induced by doxorubicin. Research in Pharmaceutical Sciences. 2021;17(1):12-21. doi:10.4103/1735-5362.329922
CR  - Birsoy K, Wang T, Chen WW, Freinkman E, Abu-Remaileh M, Sabatini DM. An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. Cell. 2015;162(3):540-551. doi:10.1016/j.cell.2015.07.016
CR  - Li Y, Park JS, Deng JH, Bai Y. Cytochrome c oxidase subunit IV is essential for assembly and respiratory function of the enzyme complex. Journal of Bioenergetics and Biomembranes. 2006;38(5-6):283-291. doi:10.1007/s10863-006-9052-z
UR  - https://doi.org/10.30569/adiyamansaglik.1325975
L1  - https://dergipark.org.tr/en/download/article-file/3257942
ER  -