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Combinational effects of ponatinib and some Turkish endemic plant extracts on breast cancer cells

Yıl 2022, , 232 - 243, 13.06.2022
https://doi.org/10.19161/etd.1126901

Öz

Aim: Breast cancer is the most common malignancy in women worldwide. Therefore, there is a need to define new strategies that can overcome the deficiencies of existing treatments. In our study, we aimed to define new herbal combination therapies that can be used to target breast cancer cells. For this purpose, we investigated the cytotoxic, apoptotic, anti-proliferative and cell cycle regulatory effects of Centaurea calolepis (CCI), Origanum sipyleum (OSM) and Phlomis lycia (PLI) plant extracts in combination with ponatinib on MCF-7 cells.


Materials and Methods: The cytotoxic effects of OSM, CCI, PLI and ponatinib on MCF-7 cells were measured in real time by xCELLigence. The median-effect equation was used for the analysis of combinations of ponatinib with CCI (p-CCI), OSM (p-OSM), PLI (p-PLI). Apoptosis, proliferation and cell cycle regulation were evaluated by flow cytometry.

Results: The IC50 doses of CCI, OSM and PLI extracts in MCF-7 cells were calculated as 59.5, 57, 44.2 μg/ml at 48 hours and 51.6, 54.21, 42.52 μg/ml at 72 hours, respectively. Combination analyses revealed that p-CCI was additive, p-OSM and p-PLI showed a moderate synergistic effect at 48th hours. It was determined that apoptosis induced by ponatinib was significantly increased with the combinations of CCI and PLI. CCI and PLI treatments exhibited moderate anti-proliferative effects on MCF-7 cells, while OSM extract suppressed proliferation most significantly. Consistent with the proliferation results, the highest G0/G1 arrest was observed with OSM treatment. It was revealed that combined p-CCI and p-PLI treatments significantly increased the anti-proliferative effect of ponatinib and caused a higher level of G0/G1 accumulation.


Conclusion: Combinations of ponatinib and CCI, OSM, PLI plant extracts exhibited anti-cancer activity in breast cancer with induction of apoptosis, suppression of proliferation and cell cycle arrest. In light of the high anti-cancer effects identified, extracts of these Turkish endemic plants may represent a potential strategy in the treatment of breast cancer patients.

Kaynakça

  • Arya GC, Kaur K, Jaitak V. Isoxazole derivatives as anticancer agent: A review on synthetic strategies, mechanism of action and SAR studies. Eur J Med Chem 2021; 221: 113511.
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69 (1): 7-34.
  • Lumachi F, Santeufemia DA, Basso SM. Current medical treatment of estrogen receptor-positive breast cancer. World J Biol Chem 2015; 6 (3): 231-9.
  • Eric I, Petek Eric A, Kristek J, Koprivcic I, Babic M. Breast Cancer in Young Women: Pathologic and Immunohistochemical Features. Acta Clin Croat 2018; 57 (3): 497-502.
  • Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, ve ark. Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J Med Chem 2010; 53 (12): 4701-19.
  • Zhou T, Commodore L, Huang WS, Wang Y, Thomas M, Keats J, ve ark. Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance. Chem Biol Drug Des 2011; 77 (1): 1-11.
  • O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, ve ark. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 2009; 16 (5): 401-12.
  • Dickson C, Spencer-Dene B, Dillon C, Fantl V. Tyrosine kinase signalling in breast cancer: fibroblast growth factors and their receptors. Breast Cancer Res 2000; 2 (3): 191-6.
  • Jitariu AA, Raica M, Cimpean AM, Suciu SC. The role of PDGF-B/PDGFR-BETA axis in the normal development and carcinogenesis of the breast. Crit Rev Oncol Hematol 2018; 131: 46-52.
  • Singh DD, Yadav DK. TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy. Biomedicines 2021; 9 (8): 876
  • Musumeci F, Greco C, Grossi G, Molinari A, Schenone S. Recent Studies on Ponatinib in Cancers Other Than Chronic Myeloid Leukemia. Cancers (Basel) 2018; 10 (11): 430
  • Shao W, Li S, Li L, Lin K, Liu X, Wang H, ve ark. Chemical genomics reveals inhibition of breast cancer lung metastasis by Ponatinib via c-Jun. Protein Cell 2019; 10 (3): 161-77.
  • Kim S, You D, Jeong Y, Yoon SY, Kim SA, Lee JE. Inhibition of platelet-derived growth factor C and their receptors additionally increases doxorubicin effects in triple-negative breast cancer cells. Eur J Pharmacol 2021; 895: 173868.
  • Kim S, You D, Jeong Y, Yoon SY, Kim SA, Lee JE. Inhibition of platelet-derived growth factor receptor synergistically increases the pharmacological effect of tamoxifen in estrogen receptor alpha positive breast cancer. Oncol Lett 2021; 21 (4): 294.
  • Tekeli Y, Sezgin M, Aktumsek A, Ozmen Guler G, Aydin Sanda M. Fatty acid composition of six Centaurea species growing in Konya, Turkey. Nat Prod Res 2010; 24 (20): 1883-9.
  • Ozbilgin A, Durmuskahya C, Kayalar H, Ertabaklar H, Gunduz C, Ural IO, ve ark. Antileishmanial activity of selected Turkish medicinal plants. Tropical Journal of Pharmaceutical Research 2014;13(12):2047-55.
  • Erel SB, Karaalp C, Bedir E, Kaehlig H, Glasl S, Khan S, ve ark. Secondary metabolites of Centaurea calolepis and evaluation of cnicin for anti-inflammatory, antioxidant, and cytotoxic activities. Pharm Biol 2011; 49 (8): 840-9.
  • Baser K, Özek T, Kürkçüoglu M, Tümen G. Composition of the essential oil of Origanum sipyleum of Turkish origin. Journal of Essential Oil Research 1992; 4 (2): 139-42.
  • Durmuşkahya C, Alp H, Hortooğlu ZS, Toktas Ü, Kayalar H. X-ray fluorescence spectroscopic determination of heavy metals and trace elements in aerial parts of Origanum sipyleum L from Turkey. Tropical Journal of Pharmaceutical Research 2016; 15 (5): 1013-5.
  • Kargıoğlu M, Cenkci S, Serteser A, Evliyaoğlu N, Konuk M, Kök MŞ, ve ark. An ethnobotanical survey of inner-West Anatolia, Turkey. Human Ecology 2008; 36 (5): 763-77.
  • Zengin G, Ferrante C, Orlando G, Zheleva-Dimitrova D, Gevrenova R, Recinella L, ve ark. Chemical profiling and pharmaco-toxicological activity of Origanum sipyleum extracts: Exploring for novel sources for potential therapeutic agents. J Food Biochem 2019; 43 (11): e13003.
  • Saracoğlu İ, Harput Üş, Çaliş İ, Ogihara Y. Phenolic Constituents From Phlomis Lycia. Turkish Journal Of Chemistry 2002; 26 (1): 133-42.
  • Fakir H, Korkmaz M, Güller B. Medicinal Plant Diversity Of Western Mediterrenean Region In Turkey. Journal Of Applied Biological Sciences 2009; 3 (2): 33-43.
  • Okcanoğlu TB, Kayabaşı Ç, Süslüer SY, Gündüz C. The Relationship Between Long Non-Coding RNA Expressions and Ponatinib in Breast Cancer. Cyprus Journal of Medical Sciences 2019; 4 (2): 125-30.
  • Dogan Sigva ZO, Balci Okcanoglu T, Biray Avci C, Yilmaz Susluer S, Kayabasi C, Turna B, ve ark. Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines. Gene 2019; 687: 261-71.
  • Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010; 70 (2): 440-6.
  • Kayabasi C, Yelken BO, Asik A, Okcanoglu TB, Sogutlu F, Gasimli R, ve ark. PI3K/mTOR dual-inhibition with VS-5584 enhances anti-leukemic efficacy of ponatinib in blasts and Ph-negative LSCs of chronic myeloid leukemia. Eur J Pharmacol 2021; 910: 174446.
  • Gulla S, Lomada D, Araveti PB, Srivastava A, Murikinati MK, Reddy KR, ve ark. Titanium dioxide nanotubes conjugated with quercetin function as an effective anticancer agent by inducing apoptosis in melanoma cells. Journal of Nanostructure in Chemistry 2021: 1-14.
  • Mughees M, Wajid S, Samim M. Cytotoxic potential of Artemisia absinthium extract loaded polymeric nanoparticles against breast cancer cells: Insight into the protein targets. Int J Pharm 2020;586:119583.
  • Talbert DR, Doherty KR, Trusk PB, Moran DM, Shell SA, Bacus S. A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity. Toxicol Sci 2015; 143 (1): 147-55.
  • Çelik Ta, Aslantürk Ös. Carpobrotus acınaiformis L. Metanol Ekstresinin Fitokimyasal Taraması ve Ekstrenin İnsan Metastatik Meme Kanseri (MCF-7) ve İnsan Kolon Kanseri (Caco-2) Hücreleri Üzerindeki Sitotoksik ve Apoptotik Etkisinin Araştırılması. Marmara Fen Bilimleri Dergisi; 30 (2): 163-75.
  • Çağlar HO, Süslüer SY, Kavaklı Ş, Gündüz C, Ertürk B, Özkınay F, ve ark. Meme kanseri kök hücrelerinde elajik asit ile indüklenmiş miRNA’ların ifadesi ve elajik asidin apoptoz üzerine etkisi. Ege Tıp Dergisi 2017; 56 (4): 183-92.
  • Altundag Em, Becer E, Gencalp D, Vatansever S. Kuersetin, Kurkumin Ve Kombinasyonlarinin Meme Kanseri Hücre Hatlari Üzerindeki Antiproliferatif Etkilerinin Araştirilmasi. Journal of Faculty of Pharmacy of Ankara University; 44 (3): 424-36.
  • Yin SY, Wei WC, Jian FY, Yang NS. Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med 2013; 2013: 302426.
  • 35. Nasr FA, Shahat AA, Alqahtani AS, Ahmed MZ, Qamar W, Al-Mishari AA, ve ark. Centaurea bruguierana inhibits cell proliferation, causes cell cycle arrest, and induces apoptosis in human MCF-7 breast carcinoma cells. Mol Biol Rep 2020; 47 (8): 6043-51.
  • Keyvanloo Shahrestanaki M, Bagheri M, Ghanadian M, Aghaei M, Jafari SM. Centaurea cyanus extracted 13-O-acetylsolstitialin A decrease Bax/Bcl-2 ratio and expression of cyclin D1/Cdk-4 to induce apoptosis and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines. J Cell Biochem 2019; 120 (10): 18309-19.
  • Bahmani F, Esmaeili S, Bashash D, Dehghan-Nayeri N, Mashati P, Gharehbaghian A. Centaurea albonitens extract enhances the therapeutic effects of Vincristine in leukemic cells by inducing apoptosis. Biomed Pharmacother 2018; 99: 598-607.
  • Al Dhaheri Y, Eid A, AbuQamar S, Attoub S, Khasawneh M, Aiche G, ve ark. Mitotic arrest and apoptosis in breast cancer cells induced by Origanum majorana extract: upregulation of TNF-alpha and downregulation of survivin and mutant p53. PLoS One 2013; 8 (2): e56649.
  • Tuncer E, Unver-Saraydin S, Tepe B, Karadayi S, Ozer H, Karadayi K, ve ark. Antitumor effects of Origanum acutidens extracts on human breast cancer. J BUON 2013; 18 (1): 77-85.
  • Kubatka P, Kello M, Kajo K, Kruzliak P, Vybohova D, Mojzis J, ve ark. Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model. Eur J Nutr 2017; 56 (3): 1303-16.
  • Kamel KM, Khalil IA, Rateb ME, Elgendy H, Elhawary S. Chitosan-Coated Cinnamon/Oregano-Loaded Solid Lipid Nanoparticles to Augment 5-Fluorouracil Cytotoxicity for Colorectal Cancer: Extract Standardization, Nanoparticle Optimization, and Cytotoxicity Evaluation. J Agric Food Chem 2017; 65 (36): 7966-81.
  • Stojkovic D, Gasic U, Drakulic D, Zengin G, Stevanovic M, Rajcevic N, ve ark. Chemical profiling, antimicrobial, anti-enzymatic, and cytotoxic properties of Phlomis fruticosa L. J Pharm Biomed Anal 2021; 195: 113884.
  • Yarmolinsky L, Budovsky A, Ben-Shabat S, Khalfin B, Gorelick J, Bishitz Y, ve ark. Recent Updates on the Phytochemistry and Pharmacological Properties of Phlomis viscosa Poiret. Rejuvenation Res 2019; 22 (4): 282-8.

Ponatinib ve Türkiye’de yetişen bazı endemik bitki ekstrelerinin kombinasyonlarının meme kanseri hücreleri üzerindeki etkileri

Yıl 2022, , 232 - 243, 13.06.2022
https://doi.org/10.19161/etd.1126901

Öz

Amaç: Meme kanseri, dünya genelinde kadınlarda en yaygın gözlenen malignansidir. Bu nedenle mevcut tedavilerin eksiklerini giderebilecek yeni stratejilerin tanımlanmasına ihtiyaç vardır. Çalışmamızda meme kanseri hücrelerinin hedeflenmesinde kullanılabilecek yeni bitkisel kombinasyon terapileri tanımlamayı hedefledik. Bu amaçla, Centaurea calolepis (CCİ), Origanum sipyleum (OSM) ve Phlomis lycia (PLİ) bitki ekstrelerinin ponatinib ile kombinasyonlarının MCF-7 hücreleri üzerindeki sitotoksik, apoptotik, anti-proliferatif ve hücre döngüsü üzerindeki etkileri araştırılmıştır.

Gereç ve Yöntem: MCF-7 hücrelerinde OSM, CCİ, PLİ ve ponatinibin sitotoksik etkileri xCELLigence ile gerçek-zamanlı olarak ölçüldü. Ponatinib ile CCİ (p-CCİ), OSM (p-OSM), PLİ (p-PLİ) kombinasyonlarının analizleri için medyan-etki denklemini kullanıldı. Apoptoz, proliferasyon, hücre döngüsü düzenlenmesi akım sitometride değerlendirildi.

Bulgular: MCF-7 hücrelerinde CCİ, OSM ve PLİ ekstrelerinin IC50 dozları sırasıyla 48. saatte 59,5, 57, 44,2 μg/ml ve 72. saatte 51,6, 54,21, 42,52 μg/ml olarak hesaplandı. Kombinasyon analizi sonuçlarına göre 48. saatte p-CCİ additif, p-OSM ve p-PLİ ılımlı sinerjistik etki sergilemekteydi. Ponatinib ile indüklenen apoptozun, CCİ ve PLİ kombinasyonlarıyla anlamlı düzeyde arttığı belirlendi. CCİ ve PLİ uygulamaları MCF-7 hücreleri üzerinde ılımlı düzeyde anti-proliferatif etki sergilerken, proliferasyonu en belirgin düzeyde OSM ekstresinin baskıladığı saptandı. Proliferasyon sonuçları ile uyumlu olarak, en yüksek G0/G1 tutulumu OSM uygulaması ile gözlendi. Kombine p-CCİ ve p-PLİ uygulamalarının ponatinibin anti-proliferatif etkisini anlamlı düzeyde arttırdıkları ve daha yüksek düzeyde G0/G1 birikimine neden oldukları ortaya koyuldu.

Sonuç: Ponatinib ile CCİ, OSM, PLİ bitki ekstrelerinin kombinasyonları apoptozu indükleyerek, proliferasyonu baskılayarak ve hücre döngüsünün durdurarak meme kanserinde anti-kanser aktivitesi sergiledi. Belirlenen yüksek anti-kanser etkilerinin ışığında, Türkiye’de yetişen bu endemik bitki ekstreleri meme kanseri tedavisinde potansiyel strateji temsil edebilir.

Kaynakça

  • Arya GC, Kaur K, Jaitak V. Isoxazole derivatives as anticancer agent: A review on synthetic strategies, mechanism of action and SAR studies. Eur J Med Chem 2021; 221: 113511.
  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69 (1): 7-34.
  • Lumachi F, Santeufemia DA, Basso SM. Current medical treatment of estrogen receptor-positive breast cancer. World J Biol Chem 2015; 6 (3): 231-9.
  • Eric I, Petek Eric A, Kristek J, Koprivcic I, Babic M. Breast Cancer in Young Women: Pathologic and Immunohistochemical Features. Acta Clin Croat 2018; 57 (3): 497-502.
  • Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, ve ark. Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J Med Chem 2010; 53 (12): 4701-19.
  • Zhou T, Commodore L, Huang WS, Wang Y, Thomas M, Keats J, ve ark. Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance. Chem Biol Drug Des 2011; 77 (1): 1-11.
  • O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, ve ark. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 2009; 16 (5): 401-12.
  • Dickson C, Spencer-Dene B, Dillon C, Fantl V. Tyrosine kinase signalling in breast cancer: fibroblast growth factors and their receptors. Breast Cancer Res 2000; 2 (3): 191-6.
  • Jitariu AA, Raica M, Cimpean AM, Suciu SC. The role of PDGF-B/PDGFR-BETA axis in the normal development and carcinogenesis of the breast. Crit Rev Oncol Hematol 2018; 131: 46-52.
  • Singh DD, Yadav DK. TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy. Biomedicines 2021; 9 (8): 876
  • Musumeci F, Greco C, Grossi G, Molinari A, Schenone S. Recent Studies on Ponatinib in Cancers Other Than Chronic Myeloid Leukemia. Cancers (Basel) 2018; 10 (11): 430
  • Shao W, Li S, Li L, Lin K, Liu X, Wang H, ve ark. Chemical genomics reveals inhibition of breast cancer lung metastasis by Ponatinib via c-Jun. Protein Cell 2019; 10 (3): 161-77.
  • Kim S, You D, Jeong Y, Yoon SY, Kim SA, Lee JE. Inhibition of platelet-derived growth factor C and their receptors additionally increases doxorubicin effects in triple-negative breast cancer cells. Eur J Pharmacol 2021; 895: 173868.
  • Kim S, You D, Jeong Y, Yoon SY, Kim SA, Lee JE. Inhibition of platelet-derived growth factor receptor synergistically increases the pharmacological effect of tamoxifen in estrogen receptor alpha positive breast cancer. Oncol Lett 2021; 21 (4): 294.
  • Tekeli Y, Sezgin M, Aktumsek A, Ozmen Guler G, Aydin Sanda M. Fatty acid composition of six Centaurea species growing in Konya, Turkey. Nat Prod Res 2010; 24 (20): 1883-9.
  • Ozbilgin A, Durmuskahya C, Kayalar H, Ertabaklar H, Gunduz C, Ural IO, ve ark. Antileishmanial activity of selected Turkish medicinal plants. Tropical Journal of Pharmaceutical Research 2014;13(12):2047-55.
  • Erel SB, Karaalp C, Bedir E, Kaehlig H, Glasl S, Khan S, ve ark. Secondary metabolites of Centaurea calolepis and evaluation of cnicin for anti-inflammatory, antioxidant, and cytotoxic activities. Pharm Biol 2011; 49 (8): 840-9.
  • Baser K, Özek T, Kürkçüoglu M, Tümen G. Composition of the essential oil of Origanum sipyleum of Turkish origin. Journal of Essential Oil Research 1992; 4 (2): 139-42.
  • Durmuşkahya C, Alp H, Hortooğlu ZS, Toktas Ü, Kayalar H. X-ray fluorescence spectroscopic determination of heavy metals and trace elements in aerial parts of Origanum sipyleum L from Turkey. Tropical Journal of Pharmaceutical Research 2016; 15 (5): 1013-5.
  • Kargıoğlu M, Cenkci S, Serteser A, Evliyaoğlu N, Konuk M, Kök MŞ, ve ark. An ethnobotanical survey of inner-West Anatolia, Turkey. Human Ecology 2008; 36 (5): 763-77.
  • Zengin G, Ferrante C, Orlando G, Zheleva-Dimitrova D, Gevrenova R, Recinella L, ve ark. Chemical profiling and pharmaco-toxicological activity of Origanum sipyleum extracts: Exploring for novel sources for potential therapeutic agents. J Food Biochem 2019; 43 (11): e13003.
  • Saracoğlu İ, Harput Üş, Çaliş İ, Ogihara Y. Phenolic Constituents From Phlomis Lycia. Turkish Journal Of Chemistry 2002; 26 (1): 133-42.
  • Fakir H, Korkmaz M, Güller B. Medicinal Plant Diversity Of Western Mediterrenean Region In Turkey. Journal Of Applied Biological Sciences 2009; 3 (2): 33-43.
  • Okcanoğlu TB, Kayabaşı Ç, Süslüer SY, Gündüz C. The Relationship Between Long Non-Coding RNA Expressions and Ponatinib in Breast Cancer. Cyprus Journal of Medical Sciences 2019; 4 (2): 125-30.
  • Dogan Sigva ZO, Balci Okcanoglu T, Biray Avci C, Yilmaz Susluer S, Kayabasi C, Turna B, ve ark. Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines. Gene 2019; 687: 261-71.
  • Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010; 70 (2): 440-6.
  • Kayabasi C, Yelken BO, Asik A, Okcanoglu TB, Sogutlu F, Gasimli R, ve ark. PI3K/mTOR dual-inhibition with VS-5584 enhances anti-leukemic efficacy of ponatinib in blasts and Ph-negative LSCs of chronic myeloid leukemia. Eur J Pharmacol 2021; 910: 174446.
  • Gulla S, Lomada D, Araveti PB, Srivastava A, Murikinati MK, Reddy KR, ve ark. Titanium dioxide nanotubes conjugated with quercetin function as an effective anticancer agent by inducing apoptosis in melanoma cells. Journal of Nanostructure in Chemistry 2021: 1-14.
  • Mughees M, Wajid S, Samim M. Cytotoxic potential of Artemisia absinthium extract loaded polymeric nanoparticles against breast cancer cells: Insight into the protein targets. Int J Pharm 2020;586:119583.
  • Talbert DR, Doherty KR, Trusk PB, Moran DM, Shell SA, Bacus S. A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity. Toxicol Sci 2015; 143 (1): 147-55.
  • Çelik Ta, Aslantürk Ös. Carpobrotus acınaiformis L. Metanol Ekstresinin Fitokimyasal Taraması ve Ekstrenin İnsan Metastatik Meme Kanseri (MCF-7) ve İnsan Kolon Kanseri (Caco-2) Hücreleri Üzerindeki Sitotoksik ve Apoptotik Etkisinin Araştırılması. Marmara Fen Bilimleri Dergisi; 30 (2): 163-75.
  • Çağlar HO, Süslüer SY, Kavaklı Ş, Gündüz C, Ertürk B, Özkınay F, ve ark. Meme kanseri kök hücrelerinde elajik asit ile indüklenmiş miRNA’ların ifadesi ve elajik asidin apoptoz üzerine etkisi. Ege Tıp Dergisi 2017; 56 (4): 183-92.
  • Altundag Em, Becer E, Gencalp D, Vatansever S. Kuersetin, Kurkumin Ve Kombinasyonlarinin Meme Kanseri Hücre Hatlari Üzerindeki Antiproliferatif Etkilerinin Araştirilmasi. Journal of Faculty of Pharmacy of Ankara University; 44 (3): 424-36.
  • Yin SY, Wei WC, Jian FY, Yang NS. Therapeutic applications of herbal medicines for cancer patients. Evid Based Complement Alternat Med 2013; 2013: 302426.
  • 35. Nasr FA, Shahat AA, Alqahtani AS, Ahmed MZ, Qamar W, Al-Mishari AA, ve ark. Centaurea bruguierana inhibits cell proliferation, causes cell cycle arrest, and induces apoptosis in human MCF-7 breast carcinoma cells. Mol Biol Rep 2020; 47 (8): 6043-51.
  • Keyvanloo Shahrestanaki M, Bagheri M, Ghanadian M, Aghaei M, Jafari SM. Centaurea cyanus extracted 13-O-acetylsolstitialin A decrease Bax/Bcl-2 ratio and expression of cyclin D1/Cdk-4 to induce apoptosis and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines. J Cell Biochem 2019; 120 (10): 18309-19.
  • Bahmani F, Esmaeili S, Bashash D, Dehghan-Nayeri N, Mashati P, Gharehbaghian A. Centaurea albonitens extract enhances the therapeutic effects of Vincristine in leukemic cells by inducing apoptosis. Biomed Pharmacother 2018; 99: 598-607.
  • Al Dhaheri Y, Eid A, AbuQamar S, Attoub S, Khasawneh M, Aiche G, ve ark. Mitotic arrest and apoptosis in breast cancer cells induced by Origanum majorana extract: upregulation of TNF-alpha and downregulation of survivin and mutant p53. PLoS One 2013; 8 (2): e56649.
  • Tuncer E, Unver-Saraydin S, Tepe B, Karadayi S, Ozer H, Karadayi K, ve ark. Antitumor effects of Origanum acutidens extracts on human breast cancer. J BUON 2013; 18 (1): 77-85.
  • Kubatka P, Kello M, Kajo K, Kruzliak P, Vybohova D, Mojzis J, ve ark. Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model. Eur J Nutr 2017; 56 (3): 1303-16.
  • Kamel KM, Khalil IA, Rateb ME, Elgendy H, Elhawary S. Chitosan-Coated Cinnamon/Oregano-Loaded Solid Lipid Nanoparticles to Augment 5-Fluorouracil Cytotoxicity for Colorectal Cancer: Extract Standardization, Nanoparticle Optimization, and Cytotoxicity Evaluation. J Agric Food Chem 2017; 65 (36): 7966-81.
  • Stojkovic D, Gasic U, Drakulic D, Zengin G, Stevanovic M, Rajcevic N, ve ark. Chemical profiling, antimicrobial, anti-enzymatic, and cytotoxic properties of Phlomis fruticosa L. J Pharm Biomed Anal 2021; 195: 113884.
  • Yarmolinsky L, Budovsky A, Ben-Shabat S, Khalfin B, Gorelick J, Bishitz Y, ve ark. Recent Updates on the Phytochemistry and Pharmacological Properties of Phlomis viscosa Poiret. Rejuvenation Res 2019; 22 (4): 282-8.
Toplam 43 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Çağla Kayabaşı 0000-0002-6797-7655

Çığır Biray Avcı 0000-0001-8251-4520

Sunde Yılmaz Süslüer 0000-0002-0535-150X

Tuğçe Balcı Okcanoğlu 0000-0003-0613-765X

Besra Özmen Yelken 0000-0002-0659-1097

Cansu Çalışkan Kurt 0000-0003-3397-6854

Bakiye Göker Bağca 0000-0002-5714-7455

Cenk Durmuşkahya 0000-0002-8092-9770

Hüsniye Kayalar 0000-0001-7882-0517

Ahmet Özbilgin 0000-0003-3613-8741

Cumhur Gündüz 0000-0002-6593-3237

Yayımlanma Tarihi 13 Haziran 2022
Gönderilme Tarihi 25 Eylül 2021
Yayımlandığı Sayı Yıl 2022

Kaynak Göster

Vancouver Kayabaşı Ç, Avcı ÇB, Yılmaz Süslüer S, Balcı Okcanoğlu T, Özmen Yelken B, Çalışkan Kurt C, Göker Bağca B, Durmuşkahya C, Kayalar H, Özbilgin A, Gündüz C. Ponatinib ve Türkiye’de yetişen bazı endemik bitki ekstrelerinin kombinasyonlarının meme kanseri hücreleri üzerindeki etkileri. ETD. 2022;61(2):232-43.

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