KUERSETİN, KURKUMİN VE KOMBİNASYONLARININ MEME KANSERİ HÜCRE HATLARI ÜZERİNDEKİ ANTİPROLİFERATİF ETKİLERİNİN ARAŞTIRILMASI

Abstract

Amaç: Meme kanseri, kadınlarda malignite ve mortalite oranı yüksek olan ve Doğu Akdeniz bölgesinde sıklıkla görülen bir kanser türüdür. Kuersetin ve kurkumin, kanser hücrelerinin büyümesini inhibe etme özelliği olduğu bilinen flavonoid türleridir. Bu çalışmanın amacı, antikanser özelliğe sahip olduğu bilinen kuersetin ve kurkumin flavonoidlerinin tek başına ve kombine kullanımının metastatik ve metastatik olmayan meme kanser hücre hatlarındaki antiproliferatif etkisinin belirlenmesidir.

Gereç ve Yöntem: Bu çalışmada, kuersetin, kurkumin ve kombinasyonları M4A4 ve MCF-7 meme kanseri hücrelerine uygulandı. Hem M4A4 hem de MCF-7 hücreleri üzerindeki antiproliferatif etkinin belirlenmesi için MTT yöntemi kullanıldı. Combosyn programı kullanılarak %50’sini inhibe eden (IC50) ve kombinasyon indeks (CI) değerleri belirlendi.

Sonuç ve Tartışma: M4A4 hücre popülasyonunun IC50 etkin kuersetin dozu 72 saat sonucunda 49 µM olarak, MCF-7 hücre popülasyonu için ise 72 saat sonunda 120 µM olarak hesaplandı. M4A4 ve MCF-7 hücrelerine uygulanan kurkumin polifenolü için IC50 dozları sırasıyla 27 µM ve 54 µM olarak belirlendi. MCF-7 hücrelerine uygulanan kuersetin:kurkumin kombinasyonlarının sinerjistik etki gösterdiği, M4A4 hücreleri için ise antagonistik etki gösterdiği belirlendi. Hücrelere farklı doz ve zamanlarda kuersetin ve kurkumin uygulanmasının sonucunda, her iki polifenolün ayrı ayrı hücre canlılığını inhibe ettiği bulundu. Elde edilen bulgular, kuersetin ve kurkumin polifenoliyle birlikte kombinasyonun metastatik olmayan meme kanserinde kullanılabileceğini gösterirken, metastatik meme kanseri için farklı kombinasyon çalışmalarına ihtiyaç duyulduğunu göstermektedir.

Keywords

• Antiproliferatif etki
• kuersetin
• kurkumin
• meme kanseri

THE INVESTIGATION OF ANTIPROLIFERATIVE EFFECTS OF QUERCETIN, CURCUMIN AND THEIR COMBINATIONS ON BREAST CANCER CELL LINES

Abstract

Objective: Breast cancer is a type of cancer that has high malignancy and mortality rates in women and is frequently seen in the Eastern Mediterranean region. Flavonoids such as quercetin and curcumin are known to have an ability to inhibit the growth of cancer cells. The aim of this study was to determine the antiproliferative effect of quercetin and curcumin which are flavonoids known to have anticancer properties on human metastatic and non metastatic breast cancer cell lines of alone and in combination usage.

Material and Method: Cell growth and cytotoxicity of quercetin, curcumin and quercetin:curcumin combinations were measured with MTT assay both on M4A4 and MCF-7 breast cancer cell lines. Combosyn program was used to determine IC50 and combination index (CI) values. 

Result and Discussion: Half-maximal inhibitory concentrations (IC50) of quercetin for 72 hours were 49 µM and 120 µM on M4A4 and MCF-7 cells, respectively. IC50 doses for curcumin on M4A4 and MCF-7 cells were determined as 27 µM and 54 µM, respectively. It was determined that quercetin:curcumin combinations applied were shown a synergistic and antagonistic effect on MCF-7 and M4A4 cells. It was found that both quercetin and curcumin treatment inhibit cell viability in a dose and time-dependent manner. Findings show that combination with quercetin and curcumin polyphenol can be used in non-metastatic breast cancer, while different combination studies are needed for metastatic breast cancer.

Keywords

• Antiproliferative effect
• quercetin
• curcumin
• breast cancer

References

1. 1. Akkuzu, M.Z., Küçüköner, M., Irtegun, S et al. (2019). Meme Kanserinde Brca-1 ve Brca-2’ de Sık Görülen Polimorfizm Mutasyonların Bölgemizde Varlığı. Dicle Med J, 46, 623–631 .
2. 2. Elbachiri, M., Fatima, S., Bouchbika, Z et al. (2017). Breast cancer in men: About 40 cases and literature review. Pan Afr. Med. J, 28, 287.
3. 3. Foley, N.M., Coll, J.M., Lowery, A.J et al. (2018). Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER−/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact? Pathol. Oncol. Res, 24, 881–884.
4. 4. Anderson, W.F, Chatterjee. N., Ershler, W.B, Brawley, O.W. (2002). Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res. Treat, 76, 27–36.
5. 5. Nadji, M., Gomez-Fernandez, C., Ganjei-Azar, P., Morales, A.R. (2005). Immunohistochemistry of Estrogen and Progesterone Receptors Reconsidered. Am. J. Clin. Pathol, 123, 21–27.
6. 6. Erić, I., Erić, A.P., Kristek, J., Koprivčić, I., Babić, M. (2018). Breast cancer in young women: Pathologic and immunohistochemical features. Acta Clin. Croat, 57, 497–502.
7. 7. Kampa, M., Nifli, A.P., Notas, G., Castanas, E. (2007). Polyphenols and cancer cell growth. Rev. Physiol. Biochem. Pharmacol, 159, 79–113.
8. 8. Birman, H. (2012). Bitkisel Flavonoid Bileşiklerinin Biyoaktiviteleri ve Muhtemel Etki Mekanizmaları. İstanbul Tıp Fakültesi Derg, 75, 46–49.

9. 9. Slimestad, R., Fossen, T., Vågen, I.M. (2007). Onions: A source of unique dietary flavonoids. J Agr Food Chem, 55, 10067–10080.
10. 10. Spagnuolo, C., Russo, M., Bilotto, S., Tedesco, I., Laratta, B., Russo, G.L. (2012). Dietary polyphenols in cancer prevention: the example of the flavonoid quercetin in leukemia. Ann. N. Y. Acad. Sci, 1259, 95–103.
11. 11. Nam, J.S., Sharma, A.R., Nguyen, L.T., Chakraborty, C., Sharma, G., Lee, S. (2016). Application of bioactive quercetin in oncotherapy: From nutrition to nanomedicine. Molecules, 21(1), E108.
12. 12. Mutlu Altundağ, E., Yılmaz, A.M., Kocturk, S., Taga, Y., Yalçın, A.S. (2017). Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells. Nutr Cancer, 70, 97-108.
13. 13. Nagahama, K., Utsimi, T., Kumano, T., Maekawa, S., Oyama, N., Kawakami, J. (2016). Discovery of a new function of curcumin which enhances its anticancer therapeutic potency. Sci. Rep, 6, 30962.
14. 14. Troselj, K., Kujundzic, R. (2014). Curcumin in Combined Cancer Therapy. Curr. Pharm. Des, 20, 6682–6696.
15. 15. Kunnumakkara, A.B., Bordoloi, D., Padmavathi, G et al. (2017). Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases. Br. J. Pharmacol, 174, 1325–1348.
16. 16. Comşa, Ş., Cîmpean, A.M., Raica, M. (2015). The story of MCF-7 breast cancer cell line: 40 Years of experience in research. Anticancer Res, 35, 3147–3154.
17. 17. Sweeney, E.E., McDaniel, R.E., Maximov, P.Y., Fan, P., Craig Jordan, V. (2012). Models and mechanisms of acquired antihormone resistance in breast cancer: Significant clinical progress despite limitations. Horm. Mol. Biol. Clin. Investig, 9, 143–163.
18. 18. Urquidi, V., Sioan, D., Kawai, K et al. (2002). Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis. Clin. Cancer Res, 8, 61–74 .
19. 19. Goodison, S., Viars, C., Grazzini, M. & Urquidi, V. (2003). The interrelationship between DRIM gene expression and cytogenetic and phenotypic characteristics in human breast tumor cell lines. BMC Genomics, 4, 39.
20. 20. Srivastava, N.S., Srivastava, R.A.K. (2019). Curcumin and quercetin synergistically inhibit cancer cell proliferation in multiple cancer cells and modulate Wnt/β-catenin signaling and apoptotic pathways in A375 cells. Phytomedicine, 52, 117–128 .
21. 21. Chou, T.C. (2010). Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res, 70, 440–446.
22. 22. Li, X., Zhou, N., Wang, J et al. (2018). Quercetin suppresses breast cancer stem cells (CD44+/CD24−) by inhibiting the PI3K/Akt/mTOR-signaling pathway. Life Sci, 196, 56–62.
23. 23. Ranganathan, S., Halagowder, D., Sivasithambaram, N.D. (2015). Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells. PLoS One, 10(10), e0141370.
24. 24. Liu, J.L., Pan, Y.Y., Chen, O et al. (2017). Curcumin inhibits MCF‑7 cells by modulating the NF‑κB signaling pathway. Oncol. Lett, 14, 5581–5584.