Araştırma Makalesi
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Arbutinin İnsan Yumurtalık Kanseri Hücre Hattında in vitro Sitotoksik Aktivitesinin Araştırılması

Yıl 2025, Cilt: 9 Sayı: 1, 99 - 102, 30.06.2025

Suna Karadeniz Saygılı , Remziye Kendirci

https://doi.org/10.31594/commagene.1685992

Öz

Arbutin kozmetik ürünlerde sıklıkla kullanılan aktif bileşiklerden biridir. Bu çalışmada arbutinin yumurtalık kanseri üzerindeki olası etkileri insan seröz kistadenoma kanser hücre hattında (SKOV3) belirlenmiştir. Arbutin sitotoksisite düzeyleri ve IC50 değerleri 3-(4,5-dimetil-2-tiyazolil)-2,5-difenil-2H-tetrazolium bromür (MTT) yöntemi kullanılarak belirlenmiştir. Uygulanan doz artışına bağlı olarak arbutinin hücreler üzerinde toksik aktiviteye sahip olduğu görülmüştür. IC50 değeri uygulanan hücrelerde yapılan immünositokimyasal analiz sonucunda arbutinin IC50 dozunda SKOV3 hücrelerinde kontrol grubuna göre Kaspaz 3 immünreaktivitesini artırdığı bulunmuştur. Arbutinin IC50 dozunda SKOV3 hücrelerinde apoptotik Kaspaz 3 aktivasyonunu artırdığı göz önüne alındığında, arbutinin bu etkilerinin ardındaki moleküler mekanizmaların aydınlatılması, tedavide yeni bir bakış açısı geliştirilmesine katkı sağlayabilir.

Anahtar Kelimeler

Arbutin Ovaryum kanseri SKOV3 sitotoksisite kaspaz-3.

Etik Beyan

Ethics committee approval is not required for this study.

Destekleyen Kurum

none

Proje Numarası

None

Teşekkür

none

Kaynakça

  • Berliere, M., Piette, N., Bernard, M., Lacroix, C., Gerday, A., Samartzi, V., Coyette, M., Roelants, F., …, & Duhoux, F.O.P. (2021). Hypnosis Sedation Reduces the Duration of Different Side Effects of Cancer Treatments in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancers, 13(16), 4147. https://doi.org/10.3390/cancers13164147
  • Chan, J.K., Teoh, D., Hu, J. M., Shin, J.Y., Osann, K., & Kapp, D.S. (2008). Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecologic oncology, 109(3), 370–376. https://doi.org/10.1016/j.ygyno.2008.02.006
  • Chen, X., Wu, Y., Dong, H., Zhang, C.Y., & Zhang, Y. (2013). Platinum-based agents for individualized cancer treatment. Current molecular medicine, 13(10), 1603–1612. https://doi.org/10.2174/1566524013666131111125515
  • Cortés, A., Cascante, M., Cárdenas, M.L., & Cornish-Bowden, A. (2001). Relationships between inhibition constants, inhibitor concentrations for 50% inhibition and types of inhibition: new ways of analysing data. The Biochemical journal, 357(Pt 1), 263–268. https://doi.org/10.1042/0264-6021:3570263
  • Gajjar, K., Ogden, G., Mujahid, M.I., & Razvi, K. (2012). Symptoms and risk factors of ovarian cancer: a survey in primary care. ISRN obstetrics and gynecology, 2012, 754197. https://doi.org/10.5402/2012/754197
  • Hazman, Ö., Sarıova, A., Bozkurt, M.F., & Ciğerci, İ.H. (2021). The anticarcinogen activity of β-arbutin on MCF-7 cells: Stimulation of apoptosis through estrogen receptor-α signal pathway, inflammation and genotoxicity. Molecular and cellular biochemistry, 476(1), 349–360. https://doi.org/10.1007/s11010-020-03911-7
  • Hazman, Ö., Evin, H., Bozkurt, M.F., & Ciğerci, İ.H. (2022). Two faces of arbutin in hepatocellular carcinoma (HepG2) cells: Anticarcinogenic effect in high concentration and protective effect against cisplatin toxicity through its antioxidant and anti-inflammatory activity in low concentration. Biologia, 77(1), 225-239. https://doi.org/10.1007/s11756-021-00921-8
  • Hu, H., Zhu, S., Tong, Y., Huang, G., Tan, B., & Yang, L. (2020). Antitumor activity of triptolide in SKOV3 cells and SKOV3/DDP in vivo and in vitro. Anti-cancer drugs, 31(5), 483–491. https://doi.org/10.1097/CAD.0000000000000894
  • Khadir, F., Pouramir, M., Joorsaraee, S.G., Feizi, F., Sorkhi, H., & Yousefi, F. (2015). The effect of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine-treated rats. Caspian journal of internal medicine, 6(4), 196–200.
  • Kim, J.Y., Cho, C.H., & Song, H.S. (2017). Targeted therapy of ovarian cancer including immune check point inhibitor. The Korean journal of internal medicine, 32(5), 798–804. https://doi.org/10.3904/kjim.2017.008
  • Li, H., Jeong, Y.M., Kim, S.Y., Kim, M.K., & Kim, D.S. (2011). Arbutin inhibits TCCSUP human bladder cancer cell proliferation via up-regulation of p21. Die Pharmazie, 66(4), 306–309. https://doi.org/10.1691/ph.2011.0785
  • Lim, Y.J., Lee, E.H., Kang, T.H., Ha, S.K., Oh, M.S., Kim, S.M., Yoon, T.J., Kang, C., Park, J.H., & Kim, S.Y. (2009). Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. Archives of pharmacal research, 32(3), 367–373. https://doi.org/10.1007/s12272-009-1309-8
  • Liu, J., Liu, X., Ma, W., Kou, W., Li, C., & Zhao, J. (2018). Anticancer activity of cucurbitacin-A in ovarian cancer cell line SKOV3 involves cell cycle arrest, apoptosis and inhibition of mTOR/PI3K/Akt signaling pathway. Journal of B.U.ON.: official journal of the Balkan Union of Oncology, 23(1), 124–128.
  • Mosmann T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods, 65(1-2), 55–63. https://doi.org/10.1016/0022-1759(83)90303-4
  • Naeem, A., Hu, P., Yang, M., Zhang, J., Liu, Y., Zhu, W., & Zheng, Q. (2022). Natural Products as Anticancer Agents: Current Status and Future Perspectives. Molecules (Basel, Switzerland), 27(23), 8367. https://doi.org/10.3390/molecules27238367
  • Nahar, L., Al-Groshi, A., Kumar, A., & Sarker, S.D. (2022). Arbutin: Occurrence in Plants, and Its Potential as an Anticancer Agent. Molecules (Basel, Switzerland), 27(24), 8786. https://doi.org/10.3390/molecules27248786
  • Pečivová, J., Nosál, R., Sviteková, K., & Mačičková, T. (2014). Arbutin and decrease of potentially toxic substances generated in human blood neutrophils. Interdisciplinary toxicology, 7(4), 195–200. https://doi.org/10.2478/intox-2014-0028
  • Qiao, L.J., Li, C.Z., Ji, A., & Feng, Q. (2025). Four meroterpenoids from the leaves of Psidium guajava L. and their cytotoxicity activities. Natural product research, 1–9. https://doi.org/10.1080/14786419.2025.2469323
  • Saeedi, M., Khezri, K., Seyed Zakaryaei, A., & Mohammadamini, H. (2021). A comprehensive review of the therapeutic potential of α-arbutin. Phytotherapy research: PTR, 35(8), 4136–4154. https://doi.org/10.1002/ptr.7076
  • Shen, X., Wang, J., Wang, J., Chen, Z., Yuan, Q., & Yan, Y. (2017). High-level De novo biosynthesis of arbutin in engineered Escherichia coli. Metabolic engineering, 42, 52–58. https://doi.org/10.1016/j.ymben.2017.06.001
  • Siegel, R.L., Miller, K.D., Wagle, N.S., & Jemal, A. (2023). Cancer statistics, 2023. CA: a cancer journal for clinicians, 73(1), 17–48. https://doi.org/10.3322/caac.21763
  • Su, Y., Sun, X., Wu, R., Zhang, X., & Tu, Y. (2020). Molecular spectroscopic behaviors of beta-arbutin in anti-skin cancer. Spectroscopy Letters, 53(3), 172–183. https://doi.org/10.1080/00387010.2020.1715441
  • Surapaneni, K. M., & Arulselvan, P. (2021). Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade. Journal of biochemical and molecular toxicology, 35(9), e22857. https://doi.org/10.1002/jbt.22857
  • Xu, K.X., Xue, M.G., Li, Z., Ye, B.C., & Zhang, B. (2022). Recent Progress on Feasible Strategies for Arbutin Production. Frontiers in bioengineering and biotechnology, 10, 914280. https://doi.org/10.3389/fbioe.2022.914280
  • Yadav, P., Yadav, R., Jain, S., & Vaidya, A. (2021). Caspase-3: A primary target for natural and synthetic compounds for cancer therapy. Chemical biology & drug design, 98(1), 144–165. https://doi.org/10.1111/cbdd.13860
  • Yang, Z., Shi, H., Chinnathambi, A., Salmen, S.H., Alharbi, S.A., Veeraraghavan, V.P., Surapaneni, K.M., & Arulselvan, P. (2021). Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade. Journal of biochemical and molecular toxicology, 35(9), e22857. https://doi.org/10.1002/jbt.22857

Investigation of in vitro Cytotoxic Activity of Arbutin on Human Ovarian Cancer Cell Line

Yıl 2025, Cilt: 9 Sayı: 1, 99 - 102, 30.06.2025

Suna Karadeniz Saygılı , Remziye Kendirci

https://doi.org/10.31594/commagene.1685992

Öz

Arbutin is one of the chemical compounds commonly found in cosmetics. Arbutin's potential effects on ovarian cancer were investigated in this study using the human serous cystadenoma cancer cell line (SKOV3). Cytotoxicity levels and IC50 values of arbutin were determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. Depending on the increase in the applied doses, arbutin was found to have toxic activity on cancer cells. As a result of the immunocytochemical analysis performed on the cells applied with the IC50 value, it was found that arbutin at the IC50 dose increased Caspase 3 immunoreactivity in SKOV3 cells compared to the control group. Considering that arbutin increased apoptotic Caspase 3 activation in SKOV3 cells at the IC50 dose, elucidation of the molecular mechanisms behind these effects of arbutin may contribute to the development of a new perspective in treatment.

Anahtar Kelimeler

Arbutin Ovarian cancer SKOV3 cytotoxicity caspase-3.

Etik Beyan

Ethics committee approval is not required for this study.

Destekleyen Kurum

None

Proje Numarası

None

Teşekkür

None

Kaynakça

  • Berliere, M., Piette, N., Bernard, M., Lacroix, C., Gerday, A., Samartzi, V., Coyette, M., Roelants, F., …, & Duhoux, F.O.P. (2021). Hypnosis Sedation Reduces the Duration of Different Side Effects of Cancer Treatments in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancers, 13(16), 4147. https://doi.org/10.3390/cancers13164147
  • Chan, J.K., Teoh, D., Hu, J. M., Shin, J.Y., Osann, K., & Kapp, D.S. (2008). Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecologic oncology, 109(3), 370–376. https://doi.org/10.1016/j.ygyno.2008.02.006
  • Chen, X., Wu, Y., Dong, H., Zhang, C.Y., & Zhang, Y. (2013). Platinum-based agents for individualized cancer treatment. Current molecular medicine, 13(10), 1603–1612. https://doi.org/10.2174/1566524013666131111125515
  • Cortés, A., Cascante, M., Cárdenas, M.L., & Cornish-Bowden, A. (2001). Relationships between inhibition constants, inhibitor concentrations for 50% inhibition and types of inhibition: new ways of analysing data. The Biochemical journal, 357(Pt 1), 263–268. https://doi.org/10.1042/0264-6021:3570263
  • Gajjar, K., Ogden, G., Mujahid, M.I., & Razvi, K. (2012). Symptoms and risk factors of ovarian cancer: a survey in primary care. ISRN obstetrics and gynecology, 2012, 754197. https://doi.org/10.5402/2012/754197
  • Hazman, Ö., Sarıova, A., Bozkurt, M.F., & Ciğerci, İ.H. (2021). The anticarcinogen activity of β-arbutin on MCF-7 cells: Stimulation of apoptosis through estrogen receptor-α signal pathway, inflammation and genotoxicity. Molecular and cellular biochemistry, 476(1), 349–360. https://doi.org/10.1007/s11010-020-03911-7
  • Hazman, Ö., Evin, H., Bozkurt, M.F., & Ciğerci, İ.H. (2022). Two faces of arbutin in hepatocellular carcinoma (HepG2) cells: Anticarcinogenic effect in high concentration and protective effect against cisplatin toxicity through its antioxidant and anti-inflammatory activity in low concentration. Biologia, 77(1), 225-239. https://doi.org/10.1007/s11756-021-00921-8
  • Hu, H., Zhu, S., Tong, Y., Huang, G., Tan, B., & Yang, L. (2020). Antitumor activity of triptolide in SKOV3 cells and SKOV3/DDP in vivo and in vitro. Anti-cancer drugs, 31(5), 483–491. https://doi.org/10.1097/CAD.0000000000000894
  • Khadir, F., Pouramir, M., Joorsaraee, S.G., Feizi, F., Sorkhi, H., & Yousefi, F. (2015). The effect of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine-treated rats. Caspian journal of internal medicine, 6(4), 196–200.
  • Kim, J.Y., Cho, C.H., & Song, H.S. (2017). Targeted therapy of ovarian cancer including immune check point inhibitor. The Korean journal of internal medicine, 32(5), 798–804. https://doi.org/10.3904/kjim.2017.008
  • Li, H., Jeong, Y.M., Kim, S.Y., Kim, M.K., & Kim, D.S. (2011). Arbutin inhibits TCCSUP human bladder cancer cell proliferation via up-regulation of p21. Die Pharmazie, 66(4), 306–309. https://doi.org/10.1691/ph.2011.0785
  • Lim, Y.J., Lee, E.H., Kang, T.H., Ha, S.K., Oh, M.S., Kim, S.M., Yoon, T.J., Kang, C., Park, J.H., & Kim, S.Y. (2009). Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. Archives of pharmacal research, 32(3), 367–373. https://doi.org/10.1007/s12272-009-1309-8
  • Liu, J., Liu, X., Ma, W., Kou, W., Li, C., & Zhao, J. (2018). Anticancer activity of cucurbitacin-A in ovarian cancer cell line SKOV3 involves cell cycle arrest, apoptosis and inhibition of mTOR/PI3K/Akt signaling pathway. Journal of B.U.ON.: official journal of the Balkan Union of Oncology, 23(1), 124–128.
  • Mosmann T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods, 65(1-2), 55–63. https://doi.org/10.1016/0022-1759(83)90303-4
  • Naeem, A., Hu, P., Yang, M., Zhang, J., Liu, Y., Zhu, W., & Zheng, Q. (2022). Natural Products as Anticancer Agents: Current Status and Future Perspectives. Molecules (Basel, Switzerland), 27(23), 8367. https://doi.org/10.3390/molecules27238367
  • Nahar, L., Al-Groshi, A., Kumar, A., & Sarker, S.D. (2022). Arbutin: Occurrence in Plants, and Its Potential as an Anticancer Agent. Molecules (Basel, Switzerland), 27(24), 8786. https://doi.org/10.3390/molecules27248786
  • Pečivová, J., Nosál, R., Sviteková, K., & Mačičková, T. (2014). Arbutin and decrease of potentially toxic substances generated in human blood neutrophils. Interdisciplinary toxicology, 7(4), 195–200. https://doi.org/10.2478/intox-2014-0028
  • Qiao, L.J., Li, C.Z., Ji, A., & Feng, Q. (2025). Four meroterpenoids from the leaves of Psidium guajava L. and their cytotoxicity activities. Natural product research, 1–9. https://doi.org/10.1080/14786419.2025.2469323
  • Saeedi, M., Khezri, K., Seyed Zakaryaei, A., & Mohammadamini, H. (2021). A comprehensive review of the therapeutic potential of α-arbutin. Phytotherapy research: PTR, 35(8), 4136–4154. https://doi.org/10.1002/ptr.7076
  • Shen, X., Wang, J., Wang, J., Chen, Z., Yuan, Q., & Yan, Y. (2017). High-level De novo biosynthesis of arbutin in engineered Escherichia coli. Metabolic engineering, 42, 52–58. https://doi.org/10.1016/j.ymben.2017.06.001
  • Siegel, R.L., Miller, K.D., Wagle, N.S., & Jemal, A. (2023). Cancer statistics, 2023. CA: a cancer journal for clinicians, 73(1), 17–48. https://doi.org/10.3322/caac.21763
  • Su, Y., Sun, X., Wu, R., Zhang, X., & Tu, Y. (2020). Molecular spectroscopic behaviors of beta-arbutin in anti-skin cancer. Spectroscopy Letters, 53(3), 172–183. https://doi.org/10.1080/00387010.2020.1715441
  • Surapaneni, K. M., & Arulselvan, P. (2021). Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade. Journal of biochemical and molecular toxicology, 35(9), e22857. https://doi.org/10.1002/jbt.22857
  • Xu, K.X., Xue, M.G., Li, Z., Ye, B.C., & Zhang, B. (2022). Recent Progress on Feasible Strategies for Arbutin Production. Frontiers in bioengineering and biotechnology, 10, 914280. https://doi.org/10.3389/fbioe.2022.914280
  • Yadav, P., Yadav, R., Jain, S., & Vaidya, A. (2021). Caspase-3: A primary target for natural and synthetic compounds for cancer therapy. Chemical biology & drug design, 98(1), 144–165. https://doi.org/10.1111/cbdd.13860
  • Yang, Z., Shi, H., Chinnathambi, A., Salmen, S.H., Alharbi, S.A., Veeraraghavan, V.P., Surapaneni, K.M., & Arulselvan, P. (2021). Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade. Journal of biochemical and molecular toxicology, 35(9), e22857. https://doi.org/10.1002/jbt.22857
Toplam 26 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hücre Gelişimi, Proliferasyon ve Ölümü
Bölüm Araştırma Makaleleri
Yazarlar

Suna Karadeniz Saygılı 0000-0003-1704-3720

Remziye Kendirci 0000-0002-6839-8823

Proje Numarası None
Erken Görünüm Tarihi 6 Haziran 2025
Yayımlanma Tarihi 30 Haziran 2025
Gönderilme Tarihi 28 Nisan 2025
Kabul Tarihi 28 Mayıs 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 9 Sayı: 1

Kaynak Göster

APA Karadeniz Saygılı, S., & Kendirci, R. (2025). Investigation of in vitro Cytotoxic Activity of Arbutin on Human Ovarian Cancer Cell Line. Commagene Journal of Biology, 9(1), 99-102. https://doi.org/10.31594/commagene.1685992
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