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Potential Anti-Cancer Effects of Extra Virgin Olive Oil and Its Phenolic Extracts on Hepatocellular Carcinoma Cells

Yıl 2023, Cilt: 7 Sayı: 2, 112 - 122, 30.12.2023
https://doi.org/10.47947/ijnls.1397191

Öz

In this study, three types of Extra Virgin olive oils (EVOO) grown in different regions of Türkiye (Kilis Yaglik, Ayvalik, Izmir Sofralik) and their phenolic extracts (EVOOP) were evaluated for their anti-cancer activity in hepatocellular carcinoma (HCC) cells (Hep40) and a complete profiling of the fatty acid, sterol and polyphenol content of these olive oils was performed by HPLC and GC method. It was shown that genetic diversity and differences in growing conditions of the olive oils studied significantly modified the phenolic composition. The biophenol content was found as 655.4 mg/kg, 508.75 mg/kg and 197.86 mg/kg in Kilis Yaglik, Izmir Sofralik and Ayvalık respectively. The highest content of oleocanthal was found in İzmir Sofralik EVOO (142.00 mg/kg) and its anti-proliferative effect was found to be high. The highest amount of hydroxytyrosol was found in Kilis Yaglik (42.14 mg/kg) and the highest amount of tyrosol was found in Izmir Sofralik (43.86 mg/kg). It was shown that there was a significant difference in the responses of polyphenols in Hep40 cells. The direct use of olive oil in Hep40 cells and the comparison with EVOOPs were evaluated for the first time in this study. The evaluation of the anti-cancer effect of EVOOs and EVOOPs was tested by MTT and the IC50 value of Ayvalik EVOO was found to be the lowest at %12.84. In EVOOPs, Izmir Sofralik was the most effective in Hep40 cells with an IC50 value of 35.40 µg/mL.

Etik Beyan

The authors declare that there is no conflict of interest and that the authors made this study's experimentation, analysis, writing, etc. all steps.

Destekleyen Kurum

This research received financial support from the Coordination of Scientific Research Projects at Ankara University (Project number: 21L0430007).

Proje Numarası

21L0430007

Teşekkür

We express our gratitude to Ankara University Scientific Research Projects Coordination Office for their support. Additionally, we acknowledge with gratitude the contributions of Hedef Ziraat (Izmir Sofralik), Buta Assos (Ayvalik), and Masmana (Kilis Yaglik), the companies from Türkiye that supplied olive oil for this study.

Kaynakça

  • Abid, K., Jabri, J., Yaich, H., Malek, A., Rekhis, J., & Kamoun, M. (2023). Bioconversion of alperujo into an alternative feed for ruminants by pretreatment with live yeasts and/or exogenous fibrolytic enzymes. Environmental Science and Pollution Research, 1-8. https://doi.org/10.1007/s11356-023-27056-4
  • Antoniou, C., & Hull, J. (2021). The anti-cancer effect of Olea europaea L. products: A review. Current Nutrition Reports, 10, 99-124. https://doi.org/10.1007/s13668-021-00350-8
  • Bakrim, S., El Omari, N., El Hachlafi, N., Bakri, Y., Lee, L.-H., & Bouyahya, A. (2022). Dietary phenolic compounds as anti-cancer natural drugs: recent update on molecular mechanisms and clinical trials. Foods, 11 (21), 3323. https://doi.org/10.3390/foods11213323
  • Bouyahya, A., Omari, N. E., Bakrim, S., Hachlafi, N. E., Balahbib, A., Wilairatana, P., & Mubarak, M. S. (2022). Advances in Dietary Phenolic Compounds to Improve Chemosensitivity of Anti-cancer Drugs. Cancers, 14(19), 4573. https://doi.org/10.3390/cancers14194573
  • Boselli, E., Di Lecce, G., Strabbioli, R., Pieralisi, G., & Frega, N. G. (2009). Are virgin olive oils obtained below 27° C better than those produced at higher temperatures?. LWT-Food Science and Technology, 42 (3), 748-757. https://doi.org/10.1016/j.lwt.2008.09.018
  • Choi, S., Kim, B. K., Yon, D. K., Lee, S. W., Lee, H. G., Chang, H. H., Park, S., Koyanagi, A., Jacob, L., & Dragioti, E. (2023). Global burden of primary liver cancer and its association with underlying aetiologies, sociodemographic status, and sex differences from 1990–2019: A DALY-based analysis of the Global Burden of Disease 2019 study. Clinical and molecular hepatology, 29(2), 433. https://doi.org/10.3350/cmh.2022.0316
  • Coccia, A., Mosca, L., Puca, R., Mangino, G., Rossi, A., & Lendaro, E. (2016). Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells. Oncol Rep, 36 (6), 3095-3104. https://doi.org/10.3892/or.2016.5150
  • Daher, S., Massarwa, M., Benson, A. A., & Khoury, T. (2018). Current and future treatment of hepatocellular carcinoma: an updated comprehensive review. Journal of Clinical and Translational Hepatology, 6 (1), 69. https://doi.org/10.14218/JCTH.2017.00031
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  • Emma, M. R., Augello, G., Di Stefano, V., Azzolina, A., Giannitrapani, L., Montalto, G., Cervello, M., & Cusimano, A. (2021). Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies. International Journal of Molecular Sciences, 22 (3), 1234. https://doi.org/10.3390/ijms22031234
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  • Goren, L., Zhang, G., Kaushik, S., Breslin, P. A. S., Du, Y. N., & Foster, D. A. (2019). (-)-Oleocanthal and (-)-oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells. PLoS One, 14 (8), e0216024. https://doi.org/10.1371/journal.pone.0216024
  • Hashim, Y. Z., Worthington, J., Allsopp, P., Ternan, N. G., Brown, E. M., McCann, M. J., Rowland, I. R., Esposto, S., Servili, M., & Gill, C. I. (2014). Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo. Food Funct, 5 (7), 1513-1519. https://doi.org/10.1039/c4fo00090k
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  • Hosseini-Zare, M. S., Sarhadi, M., Zarei, M., Thilagavathi, R., & Selvam, C. (2021). Synergistic effects of curcumin and its analogs with other bioactive compounds: A comprehensive review. European Journal of Medicinal Chemistry, 210, 113072. https://doi.org/10.1016/j.ejmech.2020.113072
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Yıl 2023, Cilt: 7 Sayı: 2, 112 - 122, 30.12.2023
https://doi.org/10.47947/ijnls.1397191

Öz

Proje Numarası

21L0430007

Kaynakça

  • Abid, K., Jabri, J., Yaich, H., Malek, A., Rekhis, J., & Kamoun, M. (2023). Bioconversion of alperujo into an alternative feed for ruminants by pretreatment with live yeasts and/or exogenous fibrolytic enzymes. Environmental Science and Pollution Research, 1-8. https://doi.org/10.1007/s11356-023-27056-4
  • Antoniou, C., & Hull, J. (2021). The anti-cancer effect of Olea europaea L. products: A review. Current Nutrition Reports, 10, 99-124. https://doi.org/10.1007/s13668-021-00350-8
  • Bakrim, S., El Omari, N., El Hachlafi, N., Bakri, Y., Lee, L.-H., & Bouyahya, A. (2022). Dietary phenolic compounds as anti-cancer natural drugs: recent update on molecular mechanisms and clinical trials. Foods, 11 (21), 3323. https://doi.org/10.3390/foods11213323
  • Bouyahya, A., Omari, N. E., Bakrim, S., Hachlafi, N. E., Balahbib, A., Wilairatana, P., & Mubarak, M. S. (2022). Advances in Dietary Phenolic Compounds to Improve Chemosensitivity of Anti-cancer Drugs. Cancers, 14(19), 4573. https://doi.org/10.3390/cancers14194573
  • Boselli, E., Di Lecce, G., Strabbioli, R., Pieralisi, G., & Frega, N. G. (2009). Are virgin olive oils obtained below 27° C better than those produced at higher temperatures?. LWT-Food Science and Technology, 42 (3), 748-757. https://doi.org/10.1016/j.lwt.2008.09.018
  • Choi, S., Kim, B. K., Yon, D. K., Lee, S. W., Lee, H. G., Chang, H. H., Park, S., Koyanagi, A., Jacob, L., & Dragioti, E. (2023). Global burden of primary liver cancer and its association with underlying aetiologies, sociodemographic status, and sex differences from 1990–2019: A DALY-based analysis of the Global Burden of Disease 2019 study. Clinical and molecular hepatology, 29(2), 433. https://doi.org/10.3350/cmh.2022.0316
  • Coccia, A., Mosca, L., Puca, R., Mangino, G., Rossi, A., & Lendaro, E. (2016). Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells. Oncol Rep, 36 (6), 3095-3104. https://doi.org/10.3892/or.2016.5150
  • Daher, S., Massarwa, M., Benson, A. A., & Khoury, T. (2018). Current and future treatment of hepatocellular carcinoma: an updated comprehensive review. Journal of Clinical and Translational Hepatology, 6 (1), 69. https://doi.org/10.14218/JCTH.2017.00031
  • Donne, R., & Lujambio, A. (2022). The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma. Hepatology. https://doi.org/10.1002/hep.32740
  • Emma, M. R., Augello, G., Di Stefano, V., Azzolina, A., Giannitrapani, L., Montalto, G., Cervello, M., & Cusimano, A. (2021). Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies. International Journal of Molecular Sciences, 22 (3), 1234. https://doi.org/10.3390/ijms22031234
  • Fang, X., Yan, Q., Liu, S., & Guan, X.-Y. (2022). Cancer stem cells in hepatocellular carcinoma: intrinsic and extrinsic molecular mechanisms in stemness regulation. International journal of molecular sciences, 23 (20), 12327. https://doi.org/10.3390/ijms232012327
  • Finicelli, M., Di Salle, A., Galderisi, U., & Peluso, G. (2022). The Mediterranean diet: an update of the clinical trials. Nutrients, 14 (14), 2956. doi/10.3390/nu14142956
  • George, E. S., Sood, S., Broughton, A., Cogan, G., Hickey, M., Chan, W. S., Sudan, S., & Nicoll, A. J. (2021). The association between diet and hepatocellular carcinoma: a systematic review. Nutrients, 13 (1), 172. https://doi.org/10.1016/j.cgh.2005.12.007
  • Goren, L., Zhang, G., Kaushik, S., Breslin, P. A. S., Du, Y. N., & Foster, D. A. (2019). (-)-Oleocanthal and (-)-oleocanthal-rich olive oils induce lysosomal membrane permeabilization in cancer cells. PLoS One, 14 (8), e0216024. https://doi.org/10.1371/journal.pone.0216024
  • Hashim, Y. Z., Worthington, J., Allsopp, P., Ternan, N. G., Brown, E. M., McCann, M. J., Rowland, I. R., Esposto, S., Servili, M., & Gill, C. I. (2014). Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo. Food Funct, 5 (7), 1513-1519. https://doi.org/10.1039/c4fo00090k
  • Hatimy, A., & Kadmiri, N. E. (2021). Benefits of phenolic compounds isolated from olive oil on prevention of cancer. Health Sciences, 2 (1), 3. https://doi.org/10.3390/ijms19082305
  • Hosseini-Zare, M. S., Sarhadi, M., Zarei, M., Thilagavathi, R., & Selvam, C. (2021). Synergistic effects of curcumin and its analogs with other bioactive compounds: A comprehensive review. European Journal of Medicinal Chemistry, 210, 113072. https://doi.org/10.1016/j.ejmech.2020.113072
  • Huang, D. Q., Singal, A. G., Kono, Y., Tan, D. J., El-Serag, H. B., & Loomba, R. (2022). Changing global epidemiology of liver cancer from 2010 to 2019: NASH is the fastest growing cause of liver cancer. Cell Metabolism, 34 (7), 969-977. https://doi.org/10.1016/j.cmet.2022.05.003
  • IOC (2017).International Olive Council. Determination of composition of triacylglycerols and composition and content of di-acylglycerols by capillary gas chromatography, in vegetable oils. https://www.internationaloliveoil.org/wp-content/uploads/2019/11/Method-COI-T.20-Doc.-No-23-Rev.1-2017-2.pdf
  • Jain, D., Murti, Y., Khan, W. U., Hossain, R., Hossain, M. N., Agrawal, K. K., Ashraf, R. A., Islam, M. T., Janmeda, P., & Taheri, Y. (2021). Roles of therapeutic bioactive compounds in hepatocellular carcinoma. Oxidative Medicine and Cellular Longevity, 2021. https://doi.org/10.1155/2021/9068850
  • Jovtchev, G., Stankov, A., Georgieva, A., Dobreva, A., Bakalova, R., Aoki, I., & Mileva, M. (2018). Cytotoxic and genotoxic potential of Bulgarian Rosa alba L. essential oil–in vitro model study. Biotechnology & Biotechnological Equipment, 32 (2), 513-519. https://doi.org/10.1080/13102818.2017.1423245
  • Kapoor, D. U., Yele, S., & Prajapati, B. G. (2023). Biophenols for cancer treatment: Current perspective and future potential. International Journal of Pharmaceutical Chemistry and Analysis, 10, 100-109. https://doi.org/10.18231/j.ijpca.2023.019
  • Kouka, P., Tsakiri, G., Tzortzi, D., Dimopoulou, S., Sarikaki, G., Stathopoulos, P., Veskoukis, A. S., Halabalaki, M., Skaltsounis, A. L., & Kouretas, D. (2019). The Polyphenolic Composition of Extracts Derived from Different Greek Extra Virgin Olive Oils Is Correlated with Their Antioxidant Potency. Oxid Med Cell Longev, 1870965. https://doi.org/10.1155/2019/1870965
  • Koulouris, A., Tsagkaris, C., Spyrou, V., Pappa, E., Troullinou, A., & Nikolaou, M. (2021). Hepatocellular carcinoma: an overview of the changing landscape of treatment options. Journal of Hepatocellular Carcinoma, 387-401. https://doi.org/10.2147/JHC.S300182
  • Kulig, M., Galanty, A., Grabowska, K., & Podolak, I. (2022). Assessment of safety and health-benefits of Citrus hystrix DC. peel essential oil, with regard to its bioactive constituents in an in vitro model of physiological and pathological skin conditions. Biomedicine & Pharmacotherapy, 151, 113151. https://doi.org/10.1016/j.biopha.2022.113151
  • Markellos, C., Ourailidou, M.-E., Gavriatopoulou, M., Halvatsiotis, P., Sergentanis, T. N., & Psaltopoulou, T. (2022). Olive oil intake and cancer risk: A systematic review and meta-analysis. PLoS One, 17 (1), e0261649. https://doi.org/10.1371/journal.pone.0261649
  • Martín‐Peláez, S., Covas, M. I., Fito, M., Kušar, A., & Pravst, I. (2013). Health effects of olive oil polyphenols: recent advances and possibilities for the use of health claims. Molecular Nutrition & Food Research, 57 (5), 760-771. https://doi.org/10.1002/mnfr.201200421
  • Mentella, M. C., Scaldaferri, F., Ricci, C., Gasbarrini, A., & Miggiano, G. A. D. (2019). Cancer and Mediterranean diet: a review. Nutrients, 11 (9), 2059. https://doi.org/10.3390/nu11092059
  • Monti, P. M., Rohsenow, D. J., Swift, R. M., Gulliver, S. B., Colby, S. M., Mueller, T. I., Brown, R. A., Gordon, A., Abrams, D. B., & Niaura, R. S. (2001). Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1‐year outcomes. Alcoholism: Clinical and Experimental Research, 25 (11), 1634-1647. https://doi.org/10.1111/j.1530-0277.2001.tb02170.x
  • Moral, R., & Escrich, E. (2022). Influence of olive oil and its components on breast cancer: Molecular mechanisms. Molecules, 27 (2), 477. https://doi.org/10.3390/molecules27020477
  • Motamedi, M., Yerushalmi, L., Haghighat, F., & Chen, Z. (2022). Recent developments in photocatalysis of industrial effluents։ A review and example of phenolic compounds degradation. Chemosphere, 296, 133688. https://doi.org/10.1016/j.chemosphere.2022.133688
  • Negro, C., Aprile, A., Luvisi, A., Nicolì, F., Nutricati, E., Vergine, M., Miceli, A., Blando, F., Sabella, E., & De Bellis, L. (2019). Phenolic profile and antioxidant activity of Italian monovarietal extra virgin olive oils. Antioxidants, 8 (6), 161. https://doi.org/10.3390/antiox8060161
  • Newman, D. J. (2018). Bioactive cyclic molecules and drug design. Expert Opinion on Drug Discovery, 13 (5), 379-385. https://doi.org/10.1080/17460441.2018.1445085
  • Özkaya, M. T. (2021). Antalya ilinde yetiştirilen Tavşan Yüeği zeytin çeşidi, Beylik ve Karazeytin zeytin tiplerinin coğrafi işaretetemel oluşurabilecek şekilde yöresel farklılıkların tspit edilmesi projesi raporu. www.antalyaborsa.org.tr
  • Panigrahy, N., Priyadarshini, A., Sahoo, M. M., Verma, A. K., Daverey, A., & Sahoo, N. K. (2022). A comprehensive review on eco-toxicity and biodegradation of phenolics: Recent progress and future outlook. Environmental Technology & Innovation, 27, 102423. https://doi.org/10.1016/j.eti.2022.102423
  • Rahaiee, S., Assadpour, E., Esfanjani, A. F., Silva, A. S., & Jafari, S. M. (2020). Application of nano/microencapsulated phenolic compounds against cancer. Advances in Colloid and Interface Science, 279, 102153. https://doi.org/10.1016/j.cis.2020.102153
  • Rizvi, N.B., Fatima, A., Busquets, R. et al. (2023). Effect of the media in the folin-ciocalteu assay for the analysis of the total phenolic content of olive products. Food Anal. Methods, in press. https://doi.org/10.1007/s12161-023-02527-z
  • Rodríguez-López, P., Lozano-Sanchez, J., Borrás-Linares, I., Emanuelli, T., Menéndez, J. A., & Segura-Carretero, A. (2020). Structure–biological activity relationships of extra-virgin olive oil phenolic compounds: Health properties and bioavailability. Antioxidants, 9 (8), 685. https://doi.org/10.3390/antiox9080685
  • Rumgay, H., Arnold, M., Ferlay, J., Lesi, O., Cabasag, C. J., Vignat, J., Laversanne, M., McGlynn, K. A., & Soerjomataram, I. (2022). Global burden of primary liver cancer in 2020 and predictions to 2040. Journal of Hepatology, 77 (6), 1598-1606. https://doi.org/10.1016/j.jhep.2022.08.021
  • Serra, F., Spatafora, F., Toni, S., Farinetti, A., Gelmini, R., & Mattioli, A. V. (2022). Polyphenols, olive oil and colonrectal cancer: the effect of Mediterranean diet in the prevention. Acta Bio Medica: Atenei Parmensis, 92, 6. https://doi.org/10.23750/abm.v92i6.10390
  • Serreli, G., & Deiana, M. (2020). Extra virgin olive oil polyphenols: Modulation of cellular pathways related to oxidant species and inflammation in aging. Cells, 9 (2), 478. https://doi.org/10.3390/cells9020478
  • Seydi, H., Nouri, K., Rezaei, N., Tamimi, A., Hassan, M., Mirzaei, H., & Vosough, M. (2023). Autophagy orchestrates resistance in hepatocellular carcinoma cells. Biomedicine & Pharmacotherapy, 161, 114487. https://doi.org/10.1016/j.biopha.2023.114487
  • Soto-Alarcon, S. A., Valenzuela, R., Valenzuela, A., & Videla, L. A. (2018). Liver protective effects of extra virgin olive oil: Interaction between its chemical composition and the cell-signaling pathways involved in protection. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders), 18 (1), 75-84. https://doi.org/10.2174/1871530317666171114120552
  • Spagnuolo, C., Moccia, S., Tedesco, I., Crescente, G., Volpe, M. G., Russo, M., & Russo, G. L. (2022). Phenolic extract from extra virgin olive oil induces different anti-proliferative pathways in human bladder cancer cell lines. Nutrients, 15 (1), 182. https://doi.org/10.3390/nu15010182
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  • Toledo, E., Salas-Salvadó, J., Donat-Vargas, C., Buil-Cosiales, P., Estruch, R., Ros, E., Corella, D., Fito, M., Hu, F. B., & Arós, F. (2015). Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: a randomized clinical trial. JAMA Internal Medicine, 175 (11), 1752-1760. https://doi.org/10.1001/jamainternmed.2015.4838
  • Torić, J., Barbarić, M., & Brala, J. (2019). Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health. Molecules (Basel, Switzerland), 24,10. https://doi.org/10.3390/molecules24102001
  • Turati, F., Trichopoulos, D., Polesel, J., Bravi, F., Rossi, M., Talamini, R., Franceschi, S., Montella, M., Trichopoulou, A., & La Vecchia, C. (2014). Mediterranean diet and hepatocellular carcinoma. Journal of Hepatology, 60 (3), 606-611. https://doi.org/10.1016/j.jhep.2013.10.034
  • Vachliotis, I. D., Valsamidis, I., & Polyzos, S. A. (2023). Tumor necrosis factor-alpha and adiponectin in nonalcoholic fatty liver disease-associated hepatocellular carcinoma. Cancers, 15 (21), 5306. https://doi.org/10.3390/cancers15215306
  • WHO. (2022). All Cancer. https://www.gdforum.org/health-diplomacy course?gclid=CjwKCAiAsIGrBhAAEiwAEzMlC5938U27Gj8QAuBG83NBybXrP4ooFl414Labk3hoc_BAbfugthJAQRoCDVAQAvD_BwE
  • Xie, P., Cecchi, L., Bellumori, M., Balli, D., Giovannelli, L., Huang, L., & Mulinacci, N. (2021). Phenolic Compounds and triterpenes in different olive tissues and olive oil by-products, and cytotoxicity on human colorectal cancer cells: the case of Frantoio, Moraiolo and Leccino cultivars (Olea europaea L.). Foods, 10, 11. https://doi.org/10.3390/foods10112823
  • Yadav, G., & Ahmaruzzaman, M. (2023). Recent development of novel nanocomposites for photocatalysis mediated remediation of phenolic derivatives: A comprehensive review. Journal of Industrial and Engineering Chemistry, 27, 18-35. https://doi.org/10.1016/j.jiec.2023.07.02
  • Yang, W., Zeng, X., Liu, Z., Zhao, Q., Tan, Y., Gao, J., et al. (2020). Diet and liver cancer risk: A narrative review of epidemiological evidence. British Journal of Nutrition, 124 (3), 330-340. https://doi.org/10.1017/S0007114520001208
  • Zhao, C., Liu, S., Gao, F., Zou, Y., Ren, Z., & Yu, Z. (2022). The role of tumor microenvironment reprogramming in primary liver cancer chemotherapy resistance. Frontiers in Oncology, 12, 1008902. https://doi.org/10.3389/fonc.2022.1008902
Toplam 54 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyokimya ve Hücre Biyolojisi (Diğer), Gıda Bilimleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Gül Kahraman 0000-0001-8724-8954

Mücahit Taha Özkaya 0000-0002-6571-5985

Özlem Yıldırım 0000-0003-1018-0335

Proje Numarası 21L0430007
Erken Görünüm Tarihi 8 Aralık 2023
Yayımlanma Tarihi 30 Aralık 2023
Gönderilme Tarihi 28 Kasım 2023
Kabul Tarihi 8 Aralık 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 7 Sayı: 2

Kaynak Göster

APA Kahraman, G., Özkaya, M. T., & Yıldırım, Ö. (2023). Potential Anti-Cancer Effects of Extra Virgin Olive Oil and Its Phenolic Extracts on Hepatocellular Carcinoma Cells. International Journal of Nature and Life Sciences, 7(2), 112-122. https://doi.org/10.47947/ijnls.1397191