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Sisplatin ve Timokinon Kombinasyonunun MCF-7 Hücrelerindeki Antiproliferatif Etkisinin Değerlendirilmesi

Year 2022, Volume 15, Issue 3, 348 - 355, 15.12.2022
https://doi.org/10.46309/biodicon.2022.1168903

Abstract

Meme kanseri, dünyada kadınlar arasında en sık en sık görülen ikinci ölüm nedeni ve en sık teşhis edilen kanser türüdür. Kemoterapötik bir ajan olan, sisplatin (CDPP), meme kanseri tedavisinde kullanılmakla birlikte ciddi yan etkilere sahiptir. Ayrıca, MCF-7 gibi meme kanseri hücrelerinin cisplatine karşı dirençli olması tedaviyi zorlaştırmaktadır. Çörek otunda bulunan ve fitokimyasal bir bileşik olan timokinon (TQ) farklı çalışmalarda antikanser ajan olarak uygulanmış ve araştırılmıştır. Bu in vitro çalışmadaki amaç, CDPP ve TQ kombinasyonunun MCF-7 hücre hattı üzerindeki antiproliferatif etkisini araştırmaktır. Bu çalışmada, MCF-7 hücreleri, 24 saat boyunca farklı TQ, CDDP konsantrasyonları ve timokinon:sisplatin kombinasyonları (TQ+CDDP) ile muamele edildi. Hücre canlılığı tayini için MTT testi ve koloni oluşumunu gözlemlemek için kristal viyole boyama yöntemleri uygulandı. MCF-7 hücre popülasyonunun %50’sini inhibe eden (IC50) değer ve kombinasyon index (CI) değerleri CompuSyn yazılım programı kullanılarak hesaplandı. MCF-7 hücreleri üzerinde TQ, CDDP ve TQ+CDDP’nin etkin dozlarının sırasıyla 58 μM, 32 μM ve 31 μM+17 μg/mL olduğu ve bu kombinasyon dozunun Fa=0.5 (IC50) olduğu durumda kombinasyon indeks değerinin 1.11 olduğu gösterildi. Sonuç olarak, TQ ve CDPP’nin tekli dozlarının MCF-7 meme kanseri hücre hattı üzerinde antiproliferatif etkiye sahip olduğu gösterildi. TQ+CDDP kombinasyonunun ise farklı Fa değerlerine denk gelen sinerjistik veya antagonistik etkilerde MCF-7 meme kanseri hücre hattına karşı antiproliferatif etki gösterdiği gözlemlendi.

References

  • Comşa, Ş., Cîmpean, A.M., Raica, M. (2015). The story of MCF-7 breast cancer cell line: 40 Years of experience in research. Anticancer Research. 35, 3147–3154.
  • Baguley, B.C., Leung, E. (2011). Heterogenity of Phenotype in Breast Cancer Cell Lines. In: Gündüz M, Gündüz E, editors. Breast Cancer. InTECH; 2011. pp. 245–256.
  • Yang, M., Li, H., Li, Y., Ruan, Y., Quan, C. (2018). Identification of genes and pathways associated with MDR in MCF-7/MDR breast cancer cells by RNA-seq analysis. Molecular Medicine Reports. 17, 6211–6226. doi:10.3892/mmr.2018.8704
  • Cepeda, V., Fuertes, M.A., Castilla, J., Alonso, C., Quevedo, C., Perez, J.M. (2008). Biochemical Mechanisms of Cisplatin Cytotoxicity. Anti-Cancer Agents in Medicinal Chemistry. 7, 3–18. doi:10.2174/187152007779314044
  • Dasari, S., Bernard Tchounwou, P. (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology. 740, 364–378. doi:10.1016/j.ejphar.2014.07.025
  • Yde, C.W., Issinger, O.G. (2006). Enhancing cisplatin sensitivity in MCF-7 human breast cancer cells by down-regulation of Bcl-2 and cyclin D1. International Journal of Oncology. 29, 1397–1404. doi:10.3892/ijo.29.6.1397
  • Ali, B.H., Blunden, G. (2003). Pharmacological and toxicological properties of Nigella sativa. Phytotherapy Research. 17, 299–305. doi:10.1002/ptr.1309
  • Darakhshan, S., Bidmeshki Pour, A., Hosseinzadeh Colagar, A., Sisakhtnezhad, S. (2015). Thymoquinone and its therapeutic potentials. Pharmacological Research. 95–96, 138–158. doi:10.1016/j.phrs.2015.03.011
  • Jafri, S.H., Glass, J., Shi, R., Zhang, S., Prince, M., Kleiner-Hancock, H. (2010). Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo. Journal of Experimental and Clinical Cancer Research. 29, 1–11. doi:10.1186/1756-9966-29-87
  • Alaufi, O.M., Noorwali, A., Zahran, F., Al-Abd, A.M., Al-Attas, S. (2017). Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro. Scientific Reports. 7, 1–12. doi:10.1038/s41598-017-13357-5
  • Chou, T.C. (2010). Drug combination studies and their synergy quantification using the chou-talalay method. Cancer Research. 70, 440–446. doi:10.1158/0008-5472.CAN-09-1947
  • Jemal, A., Bray, F., Ferlay, J. (1999). Global Cancer Statistics: 2011. CA Cancer J Clin. 49, 1,33-64. doi:10.3322/caac.20107.Available
  • Scully, O.J., Bay, B.-H., Yip, G., Yu, Y. (2012). Breast Cancer Metastasis. Cancer Genomics & Proteomics. 9, 311–320. doi:10.1007/978-981-32-9620-6_9
  • Kelland, L. (2007). The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer. 7, 573–584. doi:10.1038/nrc2167
  • Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O. ... Kroemer, G. (2012). Molecular mechanisms of cisplatin resistance. Oncogene. 31, 1869–1883. doi:10.1038/onc.2011.384
  • Pogribny, I.P., Filkowski, J.N., Tryndyak, V.P., Golubov, A., Shpyleva, S.I., Kovalchuk, O. (2010). Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. International Journal of Cancer. 127, 1785–1794. doi:10.1002/ijc.25191
  • Chavoshi, H., Vahedian, V., Saghaei, S., Pirouzpanah, M.B., Raeisi, M., Samadi, N. (2017). Adjuvant therapy with silibinin improves the efficacy of paclitaxel and cisplatin in MCF-7 breast cancer cells. Asian Pacific Journal of Cancer Prevention. 18, 2243–2247. doi:10.22034/APJCP.2017.18.8.2243
  • Jänicke, R., Anderson, M., Jänicke, R., Deveraux, Q.L., Krajewski, S., Ja, R.U. ... Marti, A. (200). Caspase-3 is essential for procaspase- 9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells Related papers. Cancer Research. 60,4386-4390.
  • Crescenzi, E., Varriale, L., Iovino, M., Chiaviello, A., Veneziani, B.M., Palumbo, G. (2004). Photodynamic therapy with indocyanine green complements and enhances low-dose cisplatin cytotoxicity in MCF-7 breast cancer cells. Molecular Cancer Therapeutics. 3, 537–544. doi:10.1158/1535-7163.537.3.5
  • Nobili, S., Lippi, D., Witort, E., Donnini, M., Bausi, L., Mini, E., ... Capaccoli, S. (2009). Natural compounds for cancer treatment and prevention. Pharmacological Research. 59, 365–378. doi:10.1016/j.phrs.2009.01.017
  • Imran, M., Rauf, A., Khan, I.A., Shahbaz, M., Qaisrani, T.B., Fatmawati, S. ... Gondal,T.A. (2018). Thymoquinone: A novel strategy to combat cancer: A review. Biomedicine and Pharmacotherapy. 106, 390–402. doi:10.1016/j.biopha.2018.06.159
  • Aslan, M., Afşar, E., Kırımlıoglu, E., Çeker, T., Yılmaz, Ç. (2021). Antiproliferative Effects of Thymoquinone in MCF-7 Breast and HepG2 Liver Cancer Cells: Possible Role of Ceramide and ER Stress. Nutrition and Cancer. 73, 460–472. doi:10.1080/01635581.2020.1751216
  • Woo, C.C., Loo, S.Y., Gee, V., Yap, C.W., Sethi, G., Kumar, A.P. ... Benn Tan, K.H. (2011). Anticancer activity of thymoquinone in breast cancer cells: Possible involvement of PPAR-γ pathway. Biochemical Pharmacology. 82, 464–475. doi:10.1016/j.bcp.2011.05.030
  • Dastjerdi, M.N., Mehdiabady, E.M., Iranpour, F.G., Bahramian, H. (2016). Effect of thymoquinone on P53 gene expression and consequence apoptosis in breast cancer cell line. International Journal of Preventive Medicine. 2016-April, 3–8. doi:10.4103/2008-7802.180412
  • Motaghed, M., Al-Hassan, F.M., Hamid, S.S. (2013). Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7. Pharmacognosy Research. 5, 200–206. doi:10.4103/0974-8490.112428
  • Aggarwal, B.B., Ichikawa, H., Garodia, P., Weerasinghe, P., Sethi, G., Bhatt, I.D. ... Nair, M.G. (2006). From traditional Ayurvedic medicine to modern medicine: Identification of therapeutic targets for suppression of inflammation and cancer. Expert Opinion on Therapeutic Targets. 10, 87–118. doi:10.1517/14728222.10.1.87

Evaluation of Antiproliferative Effect of Cisplatin and Thymoquinone Combination on MCF-7 Cells

Year 2022, Volume 15, Issue 3, 348 - 355, 15.12.2022
https://doi.org/10.46309/biodicon.2022.1168903

Abstract

Breast cancer is the second most common cause of death among women and the most frequently diagnosed cancer type in the worldwide. Cisplatin (CDPP), a chemotherapeutic agent, is used in the treatment of breast cancer, but has serious side effects. In addition, the resistance of breast cancer cells such as MCF-7 to cisplatin complicates the treatment. Thymoquinone (TQ), a phytochemical compound found in black cumin, has been applied and investigated as an anticancer agent in different studies. The aim of this in vitro study is to investigate the antiproliferative effect of CDPP and TQ combination on MCF-7 cell line. In this study, MCF-7 cells were treated with different concentrations of TQ, CDDP and thymoquinone:cisplatin combinations (TQ+CDDP) for 24 hours. MTT test were carried out for the cell viability determination and crystal violet staining methods were applied to observe colony formation. The IC50 value and combination index (CI) values that inhibit 50% of the MCF-7 cell population were calculated using the CompuSyn software program. It was shown that the IC50 dose of TQ, CDDP and TQ+CDDP on MCF-7 cells were 58 μM, 32 μM and 31 μM+17 μg/mL, respectively, and the CI value was 1.11. In conclusion, single doses of TQ and CDPP were shown to have antiproliferative effects on the MCF-7 breast cancer cell line. It was observed that the combination of TQ+CDDP showed an antiproliferative effect against MCF-7 breast cancer cell line in synergistic or antagonistic effects corresponding to different Fa values.

References

  • Comşa, Ş., Cîmpean, A.M., Raica, M. (2015). The story of MCF-7 breast cancer cell line: 40 Years of experience in research. Anticancer Research. 35, 3147–3154.
  • Baguley, B.C., Leung, E. (2011). Heterogenity of Phenotype in Breast Cancer Cell Lines. In: Gündüz M, Gündüz E, editors. Breast Cancer. InTECH; 2011. pp. 245–256.
  • Yang, M., Li, H., Li, Y., Ruan, Y., Quan, C. (2018). Identification of genes and pathways associated with MDR in MCF-7/MDR breast cancer cells by RNA-seq analysis. Molecular Medicine Reports. 17, 6211–6226. doi:10.3892/mmr.2018.8704
  • Cepeda, V., Fuertes, M.A., Castilla, J., Alonso, C., Quevedo, C., Perez, J.M. (2008). Biochemical Mechanisms of Cisplatin Cytotoxicity. Anti-Cancer Agents in Medicinal Chemistry. 7, 3–18. doi:10.2174/187152007779314044
  • Dasari, S., Bernard Tchounwou, P. (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. European Journal of Pharmacology. 740, 364–378. doi:10.1016/j.ejphar.2014.07.025
  • Yde, C.W., Issinger, O.G. (2006). Enhancing cisplatin sensitivity in MCF-7 human breast cancer cells by down-regulation of Bcl-2 and cyclin D1. International Journal of Oncology. 29, 1397–1404. doi:10.3892/ijo.29.6.1397
  • Ali, B.H., Blunden, G. (2003). Pharmacological and toxicological properties of Nigella sativa. Phytotherapy Research. 17, 299–305. doi:10.1002/ptr.1309
  • Darakhshan, S., Bidmeshki Pour, A., Hosseinzadeh Colagar, A., Sisakhtnezhad, S. (2015). Thymoquinone and its therapeutic potentials. Pharmacological Research. 95–96, 138–158. doi:10.1016/j.phrs.2015.03.011
  • Jafri, S.H., Glass, J., Shi, R., Zhang, S., Prince, M., Kleiner-Hancock, H. (2010). Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo. Journal of Experimental and Clinical Cancer Research. 29, 1–11. doi:10.1186/1756-9966-29-87
  • Alaufi, O.M., Noorwali, A., Zahran, F., Al-Abd, A.M., Al-Attas, S. (2017). Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro. Scientific Reports. 7, 1–12. doi:10.1038/s41598-017-13357-5
  • Chou, T.C. (2010). Drug combination studies and their synergy quantification using the chou-talalay method. Cancer Research. 70, 440–446. doi:10.1158/0008-5472.CAN-09-1947
  • Jemal, A., Bray, F., Ferlay, J. (1999). Global Cancer Statistics: 2011. CA Cancer J Clin. 49, 1,33-64. doi:10.3322/caac.20107.Available
  • Scully, O.J., Bay, B.-H., Yip, G., Yu, Y. (2012). Breast Cancer Metastasis. Cancer Genomics & Proteomics. 9, 311–320. doi:10.1007/978-981-32-9620-6_9
  • Kelland, L. (2007). The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer. 7, 573–584. doi:10.1038/nrc2167
  • Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O. ... Kroemer, G. (2012). Molecular mechanisms of cisplatin resistance. Oncogene. 31, 1869–1883. doi:10.1038/onc.2011.384
  • Pogribny, I.P., Filkowski, J.N., Tryndyak, V.P., Golubov, A., Shpyleva, S.I., Kovalchuk, O. (2010). Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. International Journal of Cancer. 127, 1785–1794. doi:10.1002/ijc.25191
  • Chavoshi, H., Vahedian, V., Saghaei, S., Pirouzpanah, M.B., Raeisi, M., Samadi, N. (2017). Adjuvant therapy with silibinin improves the efficacy of paclitaxel and cisplatin in MCF-7 breast cancer cells. Asian Pacific Journal of Cancer Prevention. 18, 2243–2247. doi:10.22034/APJCP.2017.18.8.2243
  • Jänicke, R., Anderson, M., Jänicke, R., Deveraux, Q.L., Krajewski, S., Ja, R.U. ... Marti, A. (200). Caspase-3 is essential for procaspase- 9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells Related papers. Cancer Research. 60,4386-4390.
  • Crescenzi, E., Varriale, L., Iovino, M., Chiaviello, A., Veneziani, B.M., Palumbo, G. (2004). Photodynamic therapy with indocyanine green complements and enhances low-dose cisplatin cytotoxicity in MCF-7 breast cancer cells. Molecular Cancer Therapeutics. 3, 537–544. doi:10.1158/1535-7163.537.3.5
  • Nobili, S., Lippi, D., Witort, E., Donnini, M., Bausi, L., Mini, E., ... Capaccoli, S. (2009). Natural compounds for cancer treatment and prevention. Pharmacological Research. 59, 365–378. doi:10.1016/j.phrs.2009.01.017
  • Imran, M., Rauf, A., Khan, I.A., Shahbaz, M., Qaisrani, T.B., Fatmawati, S. ... Gondal,T.A. (2018). Thymoquinone: A novel strategy to combat cancer: A review. Biomedicine and Pharmacotherapy. 106, 390–402. doi:10.1016/j.biopha.2018.06.159
  • Aslan, M., Afşar, E., Kırımlıoglu, E., Çeker, T., Yılmaz, Ç. (2021). Antiproliferative Effects of Thymoquinone in MCF-7 Breast and HepG2 Liver Cancer Cells: Possible Role of Ceramide and ER Stress. Nutrition and Cancer. 73, 460–472. doi:10.1080/01635581.2020.1751216
  • Woo, C.C., Loo, S.Y., Gee, V., Yap, C.W., Sethi, G., Kumar, A.P. ... Benn Tan, K.H. (2011). Anticancer activity of thymoquinone in breast cancer cells: Possible involvement of PPAR-γ pathway. Biochemical Pharmacology. 82, 464–475. doi:10.1016/j.bcp.2011.05.030
  • Dastjerdi, M.N., Mehdiabady, E.M., Iranpour, F.G., Bahramian, H. (2016). Effect of thymoquinone on P53 gene expression and consequence apoptosis in breast cancer cell line. International Journal of Preventive Medicine. 2016-April, 3–8. doi:10.4103/2008-7802.180412
  • Motaghed, M., Al-Hassan, F.M., Hamid, S.S. (2013). Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7. Pharmacognosy Research. 5, 200–206. doi:10.4103/0974-8490.112428
  • Aggarwal, B.B., Ichikawa, H., Garodia, P., Weerasinghe, P., Sethi, G., Bhatt, I.D. ... Nair, M.G. (2006). From traditional Ayurvedic medicine to modern medicine: Identification of therapeutic targets for suppression of inflammation and cancer. Expert Opinion on Therapeutic Targets. 10, 87–118. doi:10.1517/14728222.10.1.87

Details

Primary Language Turkish
Subjects Biochemistry and Molecular Biology
Journal Section Research Articles
Authors

Mete ÖZKOÇ> (Primary Author)
DOĞU AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0003-3557-4349
Kuzey Kıbrıs Türk Cumhuriyeti


Burçin Sim ÖZBAL>
DOĞU AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0002-0344-8017
Kuzey Kıbrıs Türk Cumhuriyeti


Ergül MUTLU ALTUNDAĞ>
DOĞU AKDENİZ ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0001-5355-4654
Türkiye

Early Pub Date December 16, 2022
Publication Date December 15, 2022
Submission Date August 31, 2022
Acceptance Date November 12, 2022
Published in Issue Year 2022, Volume 15, Issue 3

Cite

APA Özkoç, M. , Özbal, B. S. & Mutlu Altundağ, E. (2022). Sisplatin ve Timokinon Kombinasyonunun MCF-7 Hücrelerindeki Antiproliferatif Etkisinin Değerlendirilmesi . Biyolojik Çeşitlilik ve Koruma , 15 (3) , 348-355 . DOI: 10.46309/biodicon.2022.1168903

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