Calculus bovis Ekstraktının Antioksidan, Sitotoksik, Apoptotik/Nekrotik ve Gen Ekspresyon Düzeylerinin Belirlenmesi
Yıl 2025,
Cilt: 15 Sayı: 1, 1 - 20
Semih Dalkılıç
,
Lütfiye Kadıoğlu Dalkılıç
,
Ayşenur Çil
,
Gökhan Akay
,
İsmail Korkmaz
,
Songül Fidan
Öz
Kanser, her yıl milyonlarca insanın ölümüne neden olmakta ve tüm insanlığı etkilemektedir. 2030 yılına kadar 22 milyon yeni vaka öngörülmektedir. Standart kemoterapötik ajanların yan etkileri ve tedavi sonrası tümör tekrarı, doğal ve yenilebilir ürünlerden elde edilen moleküllerin geliştirilmesine yönlendirmiştir. Bu çalışmada, Calculus bovis ekstraktlarının kanser hücreleri üzerindeki etkileri incelenmiştir. MDA-MB-231, A549, PANC-1 ve OVCAR-3 hücre hatlarında MTT testi ile sitotoksik aktivite değerlendirilmiştir. Apoptotik/nekrotik etki çift boyama yöntemi ile analiz edilmiştir. Bax, Bcl-2, p21 ve p53 gen ekspresyon seviyeleri OVCAR-3 hücre hattında metanol ektraktında qRT-PCR yöntemiyle ölçülmüştür. Elde edilen sonuçlar gösteriyor ki aseton ekstraktı, OVCAR-3 hücre hattında belirgin sitotoksik etki göstermiştir. Aynı hücre hattında metanol ektraktında Bcl-2 gen ekspresyonunun baskılandığı ve apoptozu tetiklediği belirlenmiştir. Bulgular, Calculus bovis’in özellikle over ve meme kanseri tedavisi için potansiyel bir kemoterapötik ajan olabileceğini göstermektedir. Ekstraktın farklı kanser hücre hatlarına karşı yan etki göstermeden etkili olacağını umuyoruz. Ancak, yan etki profili henüz belirlenmediğinden araştırması gerekmektedir.
Proje Numarası
1919B012001124
Kaynakça
-
Abdullah, A.-S. H., Mohammed, A. S., Abdullah, R., Mirghani, M. E. S., & Al-Qubaisi, M. (2014). Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract. BMC Complementary and Alternative Medicine, 14, 199. https://doi.org/10.1186/1472-6882-14-199
-
Akbaş, P., Uslu, H., Uslu, G. A., & Alkan, H. (2020). Hyoscyamus reticulatus L. Tohum Ekstraktının Antimikrobiyal ve Apoptotik Etkinliğinin Araştırılması. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 24, Article 2. https://doi.org/10.19113/sdufenbed.631074
-
Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018). How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death and Differentiation, 25(1), 104–113. https://doi.org/10.1038/cdd.2017.169
-
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263. https://doi.org/10.3322/caac.21834
-
Bukholm, I. K., & Nesland, J. M. (2000). Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Archiv: An International Journal of Pathology, 436(3), 224–228. https://doi.org/10.1007/s004280050034
-
Burçak, G., & Andican, G. (2014). Oksidatif DNA Hasarı ve Yaşlanma. Cerrahpaşa Tıp Dergisi, 35(4), Article 4.
Coleman, R. A., Qiao, Z., Singh, S. K., Peng, C. S., Cianfrocco, M., Zhang, Z., Piasecka, A., Aldeborgh, H., Basishvili, G., & Liu, W. L. (2017). P53 Dynamically Directs TFIID Assembly on Target Gene Promoters. Molecular and Cellular Biology, 37(13), e00085-17. https://doi.org/10.1128/MCB.00085-17
-
Coşkun, G., & Özgür, H. (2011). Apoptoz ve Nekrozun Moleküler Mekanizması. Arşiv Kaynak Tarama Dergisi, 20, Article 3.
-
Dalkılıç, S., Korkmaz, İ., Dalkılıç, L. K., Akay, G., & Fidan, S. (2022). In vitro cytotoxic effects of Smilax aspera L. roots on cancer cell lines. Food Bioscience, 46, 101501. https://doi.org/10.1016/j.fbio.2021.101501
-
Demir, T., Akpınar, Ö., Kara, H., & Gungor, H. (2019). In Vitro Antidiabetic, Antiinflammatory, Cytotoxic, Antioxidant and Antimicrobial Activities of Pomegranate (Punica granatum L.) Peel. Akademik Gıda, 61–71. https://doi.org/10.24323/akademik-gida.544647
-
Dhanani, T., Tapadia, S., Gajbhiye, N., & Kumar, S. (2013). Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera. Arabian Journal of Chemistry. https://doi.org/10.1016/j.arabjc.2013.02.015
-
Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, 35(4), 495–516. https://doi.org/10.1080/01926230701320337
-
Ergi̇n, A., Özdi̇lek, R., & Dutucu, N. (2019). 2012-2017 Yılları Arasında Kadınlarda Görülen Kanser Türleri ve Dağılımları: Bir Üniversite Hastanesi Örneği. Kadın Sağlığı Hemşireliği Dergisi, 5(1), Article 1.
-
George, F., & John A, T. (2006). In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicology Letters, 160(2). https://doi.org/10.1016/j.toxlet.2005.07.001
-
Haileselassie, W., Mulugeta, T., Tigeneh, W., Kaba, M., & Labisso, W. L. (2019). The Situation of Cancer Treatment in Ethiopia: Challenges and Opportunities. Journal of Cancer Prevention, 24(1), 33–42. https://doi.org/10.15430/JCP.2019.24.1.33
-
He, W., Xu, Y., Zhang, C., Lu, J., Li, J., Xiang, D., Yang, J., Chang, M., & Liu, D. (2017). Hepatoprotective effect of calculus bovis sativus on nonalcoholic fatty liver disease in mice by inhibiting oxidative stress and apoptosis of hepatocytes. Drug Design, Development and Therapy, 11, 3449. https://doi.org/10.2147/DDDT.S150187
-
Horowitz, N. S., Hua, J., Powell, M. A., Gibb, R. K., Mutch, D. G., & Herzog, T. J. (2007). Novel cytotoxic agents from an unexpected source: Bile acids and ovarian tumor apoptosis. Gynecologic Oncology, 107(2), 344–349. https://doi.org/10.1016/j.ygyno.2007.07.072
-
Huang, Z., Meng, F.-Y., Lu, L.-Z., Guo, Q.-Q., Lv, C.-J., Tan, N.-H., Deng, Z., Chen, J.-Y., Zhang, Z.-S., Zou, B., Long, H.-P., Zhou, Q., Tian, S., Mei, S., & Tian, X.-F. (2024). Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer. World Journal of Gastroenterology, 30(29), 3511. https://doi.org/10.3748/wjg.v30.i29.3511
-
Jabs, J., Zickgraf, F. M., Park, J., Wagner, S., Jiang, X., Jechow, K., Kleinheinz, K., Toprak, U. H., Schneider, M. A., Meister, M., Spaich, S., Sütterlin, M., Schlesner, M., Trumpp, A., Sprick, M., Eils, R., & Conrad, C. (2017). Screening drug effects in patient‐derived cancer cells links organoid responses to genome alterations. Molecular Systems Biology. https://doi.org/10.15252/msb.20177697
-
Kadıoğlu Dalkılıç, L., Dalkilic, S., & Uygur, L. (2023). Investigation of apoptotic, cytotoxic, and antioxidant effects of Juglans regia against MDA-MB-231 and A549 cell lines. International Journal of Plant Based Pharmaceuticals, 3, 62–67. https://doi.org/10.29228/ijpbp.17
-
Karakaş, D. (2013). Kültür ortamında fibroblastların varlığında A-549 akciğer kanseri hücre hattının farklı kemoterapi ilaçlarına verdiği yanıtın araştırılması. http://hdl.handle.net/11452/6599
-
Karakaş, D., Ari, F., & Ulukaya, E. (2017). The MTT viability assay yields strikingly false-positive viabilities although the cells are killed by some plant extracts. Turkish Journal of Biology = Turk Biyoloji Dergisi, 41(6), 919–925. https://doi.org/10.3906/biy-1703-104
-
Kaya, C., Çalişkan, Y., & Yönden, Z. (2015). Apoptozis. The Medical Journal of Mustafa Kemal University, 3(11), Article 11.
-
Kong, W., Jin, C., Xiao, X., Zhao, Y., Li, Z., Zhang, P., Liu, W., & Li, X.-F. (2010). Comparative study of effects of two bile acid derivatives on Staphylococcus aureus by multiple analytical methods. Journal of Hazardous Materials, 179(1–3), 742–747. https://doi.org/10.1016/j.jhazmat.2010.03.064
-
Liu, D., Wu, T., Zhang, C.-L., Xu, Y.-J., Chang, M.-J., Li, X.-P., & Cai, H.-J. (2014). Beneficial effect of Calculus Bovis Sativus on 17α-ethynylestradiol-induced cholestasis in the rat. Life Sciences, 113(1–2), 22–30. https://doi.org/10.1016/j.lfs.2014.07.024
-
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.), 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
-
Luca, F., Salvatore, S., & Massimo, L. (2018). Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.01300
-
Mai, N. N. H., Yamaguchi, Y., Choijookhuu, N., Matsumoto, J., Nanashima, A., Takagi, H., Sato, K., Tuan, L. Q., & Hishikawa, Y. (2020). Photodynamic Therapy Using a Novel Phosphorus Tetraphenylporphyrin Induces an Anticancer Effect via Bax/Bcl-xL-related Mitochondrial Apoptosis in Biliary Cancer Cells. Acta Histochemica Et Cytochemica, 53(4), 61–72. https://doi.org/10.1267/ahc.20-00002
-
Man, S., Gao, W., Wei, C., & Liu, C. (2012). Anticancer drugs from traditional toxic Chinese medicines. Phytotherapy Research: PTR, 26(10), 1449–1465. https://doi.org/10.1002/ptr.4609
-
Menon, U., Gentry-Maharaj, A., Burnell, M., Singh, N., Ryan, A., Karpinskyj, C., Carlino, G., Taylor, J., Massingham, S. K., Raikou, M., Kalsi, J. K., Woolas, R., Manchanda, R., Arora, R., Casey, L., Dawnay, A., Dobbs, S., Leeson, S., Mould, T., … Parmar, M. (2021). Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. Lancet (London, England), 397(10290), 2182–2193. https://doi.org/10.1016/S0140-6736(21)00731-5
-
Ou, H., Hoffmann, R., González‐López, C., Doherty, G. J., Korkola, J. E., & Muñoz‐Espín, D. (2021). Cellular senescence in cancer: From mechanisms to detection. Molecular Oncology, 15(10), 2634–2671. https://doi.org/10.1002/1878-0261.12807
-
Peng, C., Tian, J., Lv, M., Huang, Y., Tian, Y., & Zhang, Z. (2014). Development and validation of a sensitive LC-MS-MS method for the simultaneous determination of multicomponent contents in artificial Calculus Bovis. Journal of Chromatographic Science, 52(2), 128–136. https://doi.org/10.1093/chromsci/bms256
-
Pérez-Herrero, E., & Fernández-Medarde, A. (2015). Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik e.V, 93, 52–79. https://doi.org/10.1016/j.ejpb.2015.03.018
-
Plengsuriyakarn, T., Viyanant, V., Eursitthichai, V., Tesana, S., Chaijaroenkul, W., Itharat, A., & Na-Bangchang, K. (2012). Cytotoxicity, toxicity, and anticancer activity of Zingiber officinale Roscoe against cholangiocarcinoma. Asian Pacific Journal of Cancer Prevention: APJCP, 13(9), 4597–4606. https://doi.org/10.7314/apjcp.2012.13.9.4597
-
Qin, X. (2008). Bilirubin would be the indispensable component for some of the most important therapeutic effects of Calculus Bovis (Niuhuang). Chinese Medical Journal, 121(5), 480.
-
Qiujun, G., Jinyin, L., Rui, L., Yebo, G., Shulin, H., Xinyao, X., Baojin, H., Conghuang, L., Wei, H., Honggang, Z., & Yanju, B. (2015). Review on the Applications and Molecular Mechanisms of Xihuang Pill in Tumor Treatment.
Evidence-Based Complementary and Alternative Medicine : eCAM, 2015. https://doi.org/10.1155/2015/854307
-
Shanmugapriya, K., Kim, H., & Kang, H. W. (2019). In vitro antitumor potential of astaxanthin nanoemulsion against cancer cells via mitochondrial mediated apoptosis. International Journal of Pharmaceutics, 560, 334–346. https://doi.org/10.1016/j.ijpharm.2019.02.015
-
Su, Z., Yang, Z., Xu, Y., Chen, Y., & Yu, Q. (2015). Apoptosis, autophagy, necroptosis, and cancer metastasis. Molecular Cancer, 14, 48. https://doi.org/10.1186/s12943-015-0321-5
-
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. https://doi.org/10.3322/caac.21660
-
Tacar, O., Sriamornsak, P., & Dass, C. R. (2013). Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of Pharmacy and Pharmacology, 65(2), 157–170. https://doi.org/10.1111/j.2042-7158.2012.01567.x
-
Tor, Y. S., Yazan, L. S., Foo, J. B., Armania, N., Cheah, Y. K., Abdullah, R., Imam, M. U., Ismail, N., & Ismail, M. (2014). Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa. BMC Complementary and Alternative Medicine, 14(1), 55. https://doi.org/10.1186/1472-6882-14-55
-
Ulukaya, E., Ozdikicioglu, F., Oral, A. Y., & Demirci, M. (2008). The MTT assay yields a relatively lower result of growth inhibition than the ATP assay depending on the chemotherapeutic drugs tested. Toxicology in Vitro: An International Journal Published in Association with BIBRA, 22(1), 232–239. https://doi.org/10.1016/j.tiv.2007.08.006
-
Wang, D. Q.-H., & Carey, M. C. (2014). Therapeutic uses of animal biles in traditional Chinese medicine: An ethnopharmacological, biophysical chemical and medicinal review. World Journal of Gastroenterology : WJG, 20(29), 9952–9975. https://doi.org/10.3748/wjg.v20.i29.9952
-
Wong, R. S. Y. (2011). Apoptosis in cancer: From pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research: CR, 30(1), 87. https://doi.org/10.1186/1756-9966-30-87
-
Xavier, C. P. R., & Palmeira, A. (2024). Special Issue: “Drug Repurposing for Cancer Therapies.” International Journal of Molecular Sciences, 25(2), 1092. https://doi.org/10.3390/ijms25021092
-
Xiang, D., Wu, T., Feng, C.-Y., Li, X.-P., Xu, Y.-J., He, W.-X., Lei, K., Cai, H.-J., Zhang, C.-L., & Liu, D. (2017). Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis. Evidence-Based Complementary and Alternative Medicine: eCAM, 2017, 1640187. https://doi.org/10.1155/2017/1640187
-
Xiang, D., Yang, J., Liu, Y., He, W., Zhang, S., Li, X., Zhang, C., & Liu, D. (2019). Calculus Bovis Sativus Improves Bile Acid Homeostasis via Farnesoid X Receptor-Mediated Signaling in Rats With Estrogen-Induced Cholestasis. Frontiers in Pharmacology, 10, 48. https://doi.org/10.3389/fphar.2019.00048
-
Yalçın, E., Azap, E., & Çavuşoğlu, K. (2017). Smilax Excelsa L. Ekstraktlarının Ames/Salmonella/Mikrozom Test Sistemi İle Antimutajenik Etkisinin Araştırılması. Duzce University Journal of Science and Technology, 5(2), Article 2.
-
Yang X., & Wu X.-Z. (2016). Revaluation of Xihuang Pill on tumor treatment: From ancient literatures to modern studies. Traditional Medicine Research, 1. https://www.tmrjournals.com/article.html?J_num=1&a_id=430
-
Yu, Z.-J., Xu, Y., Peng, W., Liu, Y.-J., Zhang, J.-M., Li, J.-S., Sun, T., & Wang, P. (2020). Calculus bovis: A review of the traditional usages, origin, chemistry, pharmacological activities and toxicology. Journal of Ethnopharmacology, 254, 112649. https://doi.org/10.1016/j.jep.2020.112649
-
Zang, Q.-C., Wang, J.-B., Kong, W.-J., Jin, C., Ma, Z.-J., Chen, J., Gong, Q.-F., & Xiao, X.-H. (2011). Searching for the main anti-bacterial components in artificial Calculus bovis using UPLC and microcalorimetry coupled with multi-linear regression analysis. Journal of Separation Science, 34(23), 3330–3338. https://doi.org/10.1002/jssc.201100500
-
Zhao, H.-T. (2024). From traditional Chinese medicine formulations to effective anticancer agents: Insights from Calculus bovis. World Journal of Gastroenterology, 30(35), 4011–4013. https://doi.org/10.3748/wjg.v30.i35.4011
-
Zhou, Q. (2017). Targeting Cyclin-Dependent Kinases in Ovarian Cancer. Cancer Investigation, 35(6), 367–376. https://doi.org/10.1080/07357907.2017.1283508
Determination of Antioxidant, Cytotoxic, Apoptotic/Necrotic and Gene Expression Levels of Calculus bovis Extract
Yıl 2025,
Cilt: 15 Sayı: 1, 1 - 20
Semih Dalkılıç
,
Lütfiye Kadıoğlu Dalkılıç
,
Ayşenur Çil
,
Gökhan Akay
,
İsmail Korkmaz
,
Songül Fidan
Öz
Cancer kills millions of people every year and affects all of humanity. 22 million new cases are projected by 2030. Side effects of standard chemotherapeutic agents and tumor recurrence after treatment have led to the development of molecules derived from natural and edible products. In this study, the impact of Calculus bovis extracts on cancer cells was examined. In MDA-MB-231, A549, PANC-1, and OVCAR-3 cell lines, cytotoxic activity was evaluated by MTT assay. The apoptotic/necrotic effect was analyzed by the double staining method. Bax, Bcl-2, p21, and p53 gene expression levels were measured by qRT-PCR in methanol extract in the OVCAR-3 cell line. The results showed that acetone extract showed a significant cytotoxic effect in the OVCAR-3 cell line. In the same cell line, the methanol extract suppressed Bcl-2 gene expression and triggered apoptosis. The findings suggest that Calculus bovis may be a potential chemotherapeutic agent, especially for the treatment of ovarian and breast cancer. We expect the extract to be effective against different cancer cell lines without side effects. However, its side effect profile is yet to be determined and needs further research.
Etik Beyan
Our study did not involve any procedures requiring ethical approval; therefore, ethical approval was not obtained.
Destekleyen Kurum
The authors declared that they did not receive funding for this study and that there was no private economic interest in conducting the research.
Proje Numarası
1919B012001124
Teşekkür
We are grateful to all researchers. This research was part of PhD Project, which is supported by The Scientific and Technological Research Council of Turkey (TUBITAK) 2209-A Program, project no:1919B012001124. We would like to thank Prof. Dr. Mustafa Kaplan for his support and the opportunity to use the laboratory facilities of Firat University Faculty of Medicine, Department of Parasitology in this study.
Kaynakça
-
Abdullah, A.-S. H., Mohammed, A. S., Abdullah, R., Mirghani, M. E. S., & Al-Qubaisi, M. (2014). Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract. BMC Complementary and Alternative Medicine, 14, 199. https://doi.org/10.1186/1472-6882-14-199
-
Akbaş, P., Uslu, H., Uslu, G. A., & Alkan, H. (2020). Hyoscyamus reticulatus L. Tohum Ekstraktının Antimikrobiyal ve Apoptotik Etkinliğinin Araştırılması. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 24, Article 2. https://doi.org/10.19113/sdufenbed.631074
-
Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018). How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death and Differentiation, 25(1), 104–113. https://doi.org/10.1038/cdd.2017.169
-
Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263. https://doi.org/10.3322/caac.21834
-
Bukholm, I. K., & Nesland, J. M. (2000). Protein expression of p53, p21 (WAF1/CIP1), bcl-2, Bax, cyclin D1 and pRb in human colon carcinomas. Virchows Archiv: An International Journal of Pathology, 436(3), 224–228. https://doi.org/10.1007/s004280050034
-
Burçak, G., & Andican, G. (2014). Oksidatif DNA Hasarı ve Yaşlanma. Cerrahpaşa Tıp Dergisi, 35(4), Article 4.
Coleman, R. A., Qiao, Z., Singh, S. K., Peng, C. S., Cianfrocco, M., Zhang, Z., Piasecka, A., Aldeborgh, H., Basishvili, G., & Liu, W. L. (2017). P53 Dynamically Directs TFIID Assembly on Target Gene Promoters. Molecular and Cellular Biology, 37(13), e00085-17. https://doi.org/10.1128/MCB.00085-17
-
Coşkun, G., & Özgür, H. (2011). Apoptoz ve Nekrozun Moleküler Mekanizması. Arşiv Kaynak Tarama Dergisi, 20, Article 3.
-
Dalkılıç, S., Korkmaz, İ., Dalkılıç, L. K., Akay, G., & Fidan, S. (2022). In vitro cytotoxic effects of Smilax aspera L. roots on cancer cell lines. Food Bioscience, 46, 101501. https://doi.org/10.1016/j.fbio.2021.101501
-
Demir, T., Akpınar, Ö., Kara, H., & Gungor, H. (2019). In Vitro Antidiabetic, Antiinflammatory, Cytotoxic, Antioxidant and Antimicrobial Activities of Pomegranate (Punica granatum L.) Peel. Akademik Gıda, 61–71. https://doi.org/10.24323/akademik-gida.544647
-
Dhanani, T., Tapadia, S., Gajbhiye, N., & Kumar, S. (2013). Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera. Arabian Journal of Chemistry. https://doi.org/10.1016/j.arabjc.2013.02.015
-
Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, 35(4), 495–516. https://doi.org/10.1080/01926230701320337
-
Ergi̇n, A., Özdi̇lek, R., & Dutucu, N. (2019). 2012-2017 Yılları Arasında Kadınlarda Görülen Kanser Türleri ve Dağılımları: Bir Üniversite Hastanesi Örneği. Kadın Sağlığı Hemşireliği Dergisi, 5(1), Article 1.
-
George, F., & John A, T. (2006). In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicology Letters, 160(2). https://doi.org/10.1016/j.toxlet.2005.07.001
-
Haileselassie, W., Mulugeta, T., Tigeneh, W., Kaba, M., & Labisso, W. L. (2019). The Situation of Cancer Treatment in Ethiopia: Challenges and Opportunities. Journal of Cancer Prevention, 24(1), 33–42. https://doi.org/10.15430/JCP.2019.24.1.33
-
He, W., Xu, Y., Zhang, C., Lu, J., Li, J., Xiang, D., Yang, J., Chang, M., & Liu, D. (2017). Hepatoprotective effect of calculus bovis sativus on nonalcoholic fatty liver disease in mice by inhibiting oxidative stress and apoptosis of hepatocytes. Drug Design, Development and Therapy, 11, 3449. https://doi.org/10.2147/DDDT.S150187
-
Horowitz, N. S., Hua, J., Powell, M. A., Gibb, R. K., Mutch, D. G., & Herzog, T. J. (2007). Novel cytotoxic agents from an unexpected source: Bile acids and ovarian tumor apoptosis. Gynecologic Oncology, 107(2), 344–349. https://doi.org/10.1016/j.ygyno.2007.07.072
-
Huang, Z., Meng, F.-Y., Lu, L.-Z., Guo, Q.-Q., Lv, C.-J., Tan, N.-H., Deng, Z., Chen, J.-Y., Zhang, Z.-S., Zou, B., Long, H.-P., Zhou, Q., Tian, S., Mei, S., & Tian, X.-F. (2024). Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer. World Journal of Gastroenterology, 30(29), 3511. https://doi.org/10.3748/wjg.v30.i29.3511
-
Jabs, J., Zickgraf, F. M., Park, J., Wagner, S., Jiang, X., Jechow, K., Kleinheinz, K., Toprak, U. H., Schneider, M. A., Meister, M., Spaich, S., Sütterlin, M., Schlesner, M., Trumpp, A., Sprick, M., Eils, R., & Conrad, C. (2017). Screening drug effects in patient‐derived cancer cells links organoid responses to genome alterations. Molecular Systems Biology. https://doi.org/10.15252/msb.20177697
-
Kadıoğlu Dalkılıç, L., Dalkilic, S., & Uygur, L. (2023). Investigation of apoptotic, cytotoxic, and antioxidant effects of Juglans regia against MDA-MB-231 and A549 cell lines. International Journal of Plant Based Pharmaceuticals, 3, 62–67. https://doi.org/10.29228/ijpbp.17
-
Karakaş, D. (2013). Kültür ortamında fibroblastların varlığında A-549 akciğer kanseri hücre hattının farklı kemoterapi ilaçlarına verdiği yanıtın araştırılması. http://hdl.handle.net/11452/6599
-
Karakaş, D., Ari, F., & Ulukaya, E. (2017). The MTT viability assay yields strikingly false-positive viabilities although the cells are killed by some plant extracts. Turkish Journal of Biology = Turk Biyoloji Dergisi, 41(6), 919–925. https://doi.org/10.3906/biy-1703-104
-
Kaya, C., Çalişkan, Y., & Yönden, Z. (2015). Apoptozis. The Medical Journal of Mustafa Kemal University, 3(11), Article 11.
-
Kong, W., Jin, C., Xiao, X., Zhao, Y., Li, Z., Zhang, P., Liu, W., & Li, X.-F. (2010). Comparative study of effects of two bile acid derivatives on Staphylococcus aureus by multiple analytical methods. Journal of Hazardous Materials, 179(1–3), 742–747. https://doi.org/10.1016/j.jhazmat.2010.03.064
-
Liu, D., Wu, T., Zhang, C.-L., Xu, Y.-J., Chang, M.-J., Li, X.-P., & Cai, H.-J. (2014). Beneficial effect of Calculus Bovis Sativus on 17α-ethynylestradiol-induced cholestasis in the rat. Life Sciences, 113(1–2), 22–30. https://doi.org/10.1016/j.lfs.2014.07.024
-
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.), 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
-
Luca, F., Salvatore, S., & Massimo, L. (2018). Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.01300
-
Mai, N. N. H., Yamaguchi, Y., Choijookhuu, N., Matsumoto, J., Nanashima, A., Takagi, H., Sato, K., Tuan, L. Q., & Hishikawa, Y. (2020). Photodynamic Therapy Using a Novel Phosphorus Tetraphenylporphyrin Induces an Anticancer Effect via Bax/Bcl-xL-related Mitochondrial Apoptosis in Biliary Cancer Cells. Acta Histochemica Et Cytochemica, 53(4), 61–72. https://doi.org/10.1267/ahc.20-00002
-
Man, S., Gao, W., Wei, C., & Liu, C. (2012). Anticancer drugs from traditional toxic Chinese medicines. Phytotherapy Research: PTR, 26(10), 1449–1465. https://doi.org/10.1002/ptr.4609
-
Menon, U., Gentry-Maharaj, A., Burnell, M., Singh, N., Ryan, A., Karpinskyj, C., Carlino, G., Taylor, J., Massingham, S. K., Raikou, M., Kalsi, J. K., Woolas, R., Manchanda, R., Arora, R., Casey, L., Dawnay, A., Dobbs, S., Leeson, S., Mould, T., … Parmar, M. (2021). Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. Lancet (London, England), 397(10290), 2182–2193. https://doi.org/10.1016/S0140-6736(21)00731-5
-
Ou, H., Hoffmann, R., González‐López, C., Doherty, G. J., Korkola, J. E., & Muñoz‐Espín, D. (2021). Cellular senescence in cancer: From mechanisms to detection. Molecular Oncology, 15(10), 2634–2671. https://doi.org/10.1002/1878-0261.12807
-
Peng, C., Tian, J., Lv, M., Huang, Y., Tian, Y., & Zhang, Z. (2014). Development and validation of a sensitive LC-MS-MS method for the simultaneous determination of multicomponent contents in artificial Calculus Bovis. Journal of Chromatographic Science, 52(2), 128–136. https://doi.org/10.1093/chromsci/bms256
-
Pérez-Herrero, E., & Fernández-Medarde, A. (2015). Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik e.V, 93, 52–79. https://doi.org/10.1016/j.ejpb.2015.03.018
-
Plengsuriyakarn, T., Viyanant, V., Eursitthichai, V., Tesana, S., Chaijaroenkul, W., Itharat, A., & Na-Bangchang, K. (2012). Cytotoxicity, toxicity, and anticancer activity of Zingiber officinale Roscoe against cholangiocarcinoma. Asian Pacific Journal of Cancer Prevention: APJCP, 13(9), 4597–4606. https://doi.org/10.7314/apjcp.2012.13.9.4597
-
Qin, X. (2008). Bilirubin would be the indispensable component for some of the most important therapeutic effects of Calculus Bovis (Niuhuang). Chinese Medical Journal, 121(5), 480.
-
Qiujun, G., Jinyin, L., Rui, L., Yebo, G., Shulin, H., Xinyao, X., Baojin, H., Conghuang, L., Wei, H., Honggang, Z., & Yanju, B. (2015). Review on the Applications and Molecular Mechanisms of Xihuang Pill in Tumor Treatment.
Evidence-Based Complementary and Alternative Medicine : eCAM, 2015. https://doi.org/10.1155/2015/854307
-
Shanmugapriya, K., Kim, H., & Kang, H. W. (2019). In vitro antitumor potential of astaxanthin nanoemulsion against cancer cells via mitochondrial mediated apoptosis. International Journal of Pharmaceutics, 560, 334–346. https://doi.org/10.1016/j.ijpharm.2019.02.015
-
Su, Z., Yang, Z., Xu, Y., Chen, Y., & Yu, Q. (2015). Apoptosis, autophagy, necroptosis, and cancer metastasis. Molecular Cancer, 14, 48. https://doi.org/10.1186/s12943-015-0321-5
-
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. https://doi.org/10.3322/caac.21660
-
Tacar, O., Sriamornsak, P., & Dass, C. R. (2013). Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of Pharmacy and Pharmacology, 65(2), 157–170. https://doi.org/10.1111/j.2042-7158.2012.01567.x
-
Tor, Y. S., Yazan, L. S., Foo, J. B., Armania, N., Cheah, Y. K., Abdullah, R., Imam, M. U., Ismail, N., & Ismail, M. (2014). Induction of apoptosis through oxidative stress-related pathways in MCF-7, human breast cancer cells, by ethyl acetate extract of Dillenia suffruticosa. BMC Complementary and Alternative Medicine, 14(1), 55. https://doi.org/10.1186/1472-6882-14-55
-
Ulukaya, E., Ozdikicioglu, F., Oral, A. Y., & Demirci, M. (2008). The MTT assay yields a relatively lower result of growth inhibition than the ATP assay depending on the chemotherapeutic drugs tested. Toxicology in Vitro: An International Journal Published in Association with BIBRA, 22(1), 232–239. https://doi.org/10.1016/j.tiv.2007.08.006
-
Wang, D. Q.-H., & Carey, M. C. (2014). Therapeutic uses of animal biles in traditional Chinese medicine: An ethnopharmacological, biophysical chemical and medicinal review. World Journal of Gastroenterology : WJG, 20(29), 9952–9975. https://doi.org/10.3748/wjg.v20.i29.9952
-
Wong, R. S. Y. (2011). Apoptosis in cancer: From pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research: CR, 30(1), 87. https://doi.org/10.1186/1756-9966-30-87
-
Xavier, C. P. R., & Palmeira, A. (2024). Special Issue: “Drug Repurposing for Cancer Therapies.” International Journal of Molecular Sciences, 25(2), 1092. https://doi.org/10.3390/ijms25021092
-
Xiang, D., Wu, T., Feng, C.-Y., Li, X.-P., Xu, Y.-J., He, W.-X., Lei, K., Cai, H.-J., Zhang, C.-L., & Liu, D. (2017). Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis. Evidence-Based Complementary and Alternative Medicine: eCAM, 2017, 1640187. https://doi.org/10.1155/2017/1640187
-
Xiang, D., Yang, J., Liu, Y., He, W., Zhang, S., Li, X., Zhang, C., & Liu, D. (2019). Calculus Bovis Sativus Improves Bile Acid Homeostasis via Farnesoid X Receptor-Mediated Signaling in Rats With Estrogen-Induced Cholestasis. Frontiers in Pharmacology, 10, 48. https://doi.org/10.3389/fphar.2019.00048
-
Yalçın, E., Azap, E., & Çavuşoğlu, K. (2017). Smilax Excelsa L. Ekstraktlarının Ames/Salmonella/Mikrozom Test Sistemi İle Antimutajenik Etkisinin Araştırılması. Duzce University Journal of Science and Technology, 5(2), Article 2.
-
Yang X., & Wu X.-Z. (2016). Revaluation of Xihuang Pill on tumor treatment: From ancient literatures to modern studies. Traditional Medicine Research, 1. https://www.tmrjournals.com/article.html?J_num=1&a_id=430
-
Yu, Z.-J., Xu, Y., Peng, W., Liu, Y.-J., Zhang, J.-M., Li, J.-S., Sun, T., & Wang, P. (2020). Calculus bovis: A review of the traditional usages, origin, chemistry, pharmacological activities and toxicology. Journal of Ethnopharmacology, 254, 112649. https://doi.org/10.1016/j.jep.2020.112649
-
Zang, Q.-C., Wang, J.-B., Kong, W.-J., Jin, C., Ma, Z.-J., Chen, J., Gong, Q.-F., & Xiao, X.-H. (2011). Searching for the main anti-bacterial components in artificial Calculus bovis using UPLC and microcalorimetry coupled with multi-linear regression analysis. Journal of Separation Science, 34(23), 3330–3338. https://doi.org/10.1002/jssc.201100500
-
Zhao, H.-T. (2024). From traditional Chinese medicine formulations to effective anticancer agents: Insights from Calculus bovis. World Journal of Gastroenterology, 30(35), 4011–4013. https://doi.org/10.3748/wjg.v30.i35.4011
-
Zhou, Q. (2017). Targeting Cyclin-Dependent Kinases in Ovarian Cancer. Cancer Investigation, 35(6), 367–376. https://doi.org/10.1080/07357907.2017.1283508