Yıl: 2021 Cilt: 46 Sayı: 1 Sayfa Aralığı: 13 - 22 Metin Dili: İngilizce İndeks Tarihi: 25-05-2022

Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability

Öz:
Many challenges of hepatocellular carcinoma treatment, such as side effects and drug resistance, still remain. Therefore, new improvements with high pharmaceutical function and low toxicity are needed. Recently, the efficacy of the combination therapy of antineoplastic drugs with natural products like pycnogenol has garnered attention. Pycnogenol® is a standardized extract from the bark of Pinus pinaster and consists of phenolic compounds. Pycnogenol is considered complementary in the treatments of some cancer besides its good tolerability and high safety. This study aims to reveal the synergistic effects of pycnogenol combination with cisplatin and its relation to human hepatocellular carcinoma (HepG2) cell viability. Effects of single and combined treatment on cell viability were evaluated in Chinese hamster lung fibroblasts (V79) and HepG2 cells using MTT assay. In HepG2 cells, this combined treatment showed a more cytotoxic effect than singledose groups. Pycnogenol increased the cytotoxicity of cisplatin at 500 μM for 24 h; at 250-500 μM for 48 h in V79 cells; and also, at 125-500 μM for 24 h; at 62.5-500 μM for 48 h in HepG2 cells (p<0.05). Our study is the first study to show that pycnogenol treatment with cisplatin has been combined in the HepG2 cell line. As a result, pycnogenol induced cisplatin cytotoxicity via combined treatment on HepG2 cells and exhibited a synergistic effect with cisplatin. In conclusion, pycnogenol may play a role in the chemotherapy of hepatocellular carcinoma; however, further studies are required to confirm their interactions with cisplatin.
Anahtar Kelime:

Piknogenol ve Sisplatin ile Kombinasyonlarının Hepatoselüler Karsinom Hücre Canlılığı Üzerine Etkileri

Öz:
Hepatoselüler karsinom tedavisinin yan etkiler ve ilaç direnci gibi birçok zorluğu devam etmektedir. Bu nedenle, farmasötik fonksiyonu yükseltecek ve toksisiteyi düşürecek yeni iyileştirmelere ihtiyaç vardır. Son zamanlarda, antineoplastik ilaçların piknogenol gibi doğal ürünlerle kombinasyonel tedavisinin etkinliği dikkat çekmektedir. Pycnogenol®, Pinus pinaster kabuğundan standartlaştırılmış bir ekstrakt olup fenolik bileşiklerden oluşur. Pycnogenolün, iyi tolere edilebilirliği ve yüksek güvenliği yanı sıra bazı kanserlerin tedavisinde de tamamlayıcı olduğu düşünülmektedir. Bu çalışmanın amacı, sisplatin ile piknogenol kombinasyonunun sinerjik etkilerini, bu etkilerin insan hepatosellüler karsinom (HepG2) hücre canlılığı ile nasıl bir ilişki olduğunu ortaya çıkarmaktır. Tek başlarına ve kombine olarak tedavinin hücre canlılığı üzerindeki etkileri, Çin hamsteri akciğer fibroblastlarında (V79) ve HepG2 hücrelerinde MTT kullanılarak değerlendirildi. HepG2 hücrelerindeki bu kombinasyon tedavi, tek doz gruplarından daha fazla sitotoksik etki gösterdi. Piknogenol, sisplatinin sitotoksisitesini V79 hücrelerinde 24 saatlik inkübasyonda 500 μM, 48 saatlik 250-500 μM konsantrasyonda ve ayrıca HepG2 hücrelerinde 24 saat için 125-500 μM, 48 saat için 62.5-500 μM’de anlamlı artırdı (p <0.05). Çalışmamız HepG2 hücre hattında piknogenolün sisplatin ile tedavisinin kombine edildiğini gösteren ilk çalışmadır. Sonuç olarak, Pycnogenol HepG2 hücreleri üzerinde kombine tedavi ile sisplatin sitotoksisitesini indükledi ve sisplatin ile sinerjistik bir etki gösterdi. Sonuç olarak, piknogenol, hepatosellüler karsinomun kemoterapisinde rol oynayabilir; bununla birlikte, sisplatin ile etkileşimlerini doğrulamak için daha ileri çalışmalara ihtiyaç vardır.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • Becit, M., & Aydın, S. (2020) An In Vitro Study on the Interactions of Pycnogenol® with Cisplatin in Human Cervical Cancer Cells. Turkish Journal of Pharmaceutical Sciences, 17(1), 1-6.
  • Belcaro, G., Cesarone, MR., Genovesi, D., Ledda, A., Vinciguerra, G., Ricci, A., & et al. (2008). Pycnogenol may alleviate adverse effects in oncologic treatment. Panminevra Med,50(3), 227-34.
  • Buz’Zard, AR., & Lau, BHS. (2007). Pycnogenol® reduces Talc-induced Neoplastic Transformation in Human Ovarian Cell Cultures. Phytotherapy Research, 21(6), 579-586.
  • Cheng, Y., Zhao, P., Wu, S., Yang, T., Chen, Y., Zhang, X., & et al. (2018). Cisplatin and Curcumin Coloaded Nano-liposomes for the Treatment of Hepatocellular Carcinoma. International Journal of Pharmaceutics, 545(1-2), 261-273.
  • D’Andrea, G. (2010). Pycnogenol: A blend of procyanidins with multifaceted therapeutic applications? Fitoterapia, 81(7), 724-36.
  • Dugbartey, GJ., Peppone LJ. & Graaf, IAM.de. (2016). An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures. Toxicology, 371, 58-66. doi. org/10.1016/j.tox.2016.10.001
  • Eryilmaz, A., Eliyatkin, N., Demirci, B., Basal, Y., Kurt Omurlu, I., Gunel, C., & et al. (2016). Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats. Pharmaceutical Biology, 54(11), 2777-2781.
  • Florea, AM., & Busselberg D. (2011). Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel), 3(1), 1351-71.
  • Grazie, ML., Biagini, MR., Tarocchi, M., Polvani, S., & Galli, A. (2017). Chemotherapy for hepatocellular carcinoma: The present and the future. World J Hepatol, 9(21), 907-20.
  • Harati, K., Slodnik, P., Chromik, AM., Behr, B., Goertz, O., Hirsch, T., & et al. (2015). Pro‑apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells. International Journal of Oncology, 46(4), 1629-36.
  • Huang, WW., Yang, JS., Lin, CF., Ho, WJ., & Lee, MR. (2005). Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL-60 cells. Leukemia Research,29(6),685-92.
  • Huynh, H.T., & Teel, R.W. (2000), Selective induction of apoptosis in human mammary cancer cells (MCF- 7) by pycnogenol, Anticancer Res, 20 (4), 2417-20.
  • Icel, E., Uçak, T., Agcayazi, B., Karakurt, Y., Yilmaz, H., Keskin Çimen, F., & et al. (2018). Effects of Pycnogenol on cisplatin-induced optic nerve injury: an experimental study. Cutaneous and Ocular Toxicology, 37(4), 396-400.
  • Ko, JW., Lee, IC., Park, SH., Moon, C., Kang, SS., Kim, SH., & et al. (2014). Protective effects of pine bark extract against cisplatin-induced hepatotoxicity and oxidative stress in rats. Laboratory Animal Research, 30(4), 174-180.
  • Lee, IC., Ko, JW., Park, SH., Shin, NR., Shin, IS., Kim, YB., & et al. (2017). Ameliorative effects of pine bark extract on cisplatin-induced acute kidney injury in rats. Ren Fail. 39(1), 363-371.
  • van Meerloo, J., Kaspers, GJ., & Cloos, J. (2011). Cell sensitivity assays: the MTT assay. Methods in Molecular Biology, 731, 237-45.
  • Nurcahyanti, AD., & Wink, M. (2016). L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells. J-PEER | Purdue University Press Open Access Journals, 4:e1542.
  • Rohdewald, P. (2005). “Pycnogenol®, French maritime pine bark extract,” in Encyclopedia of dietary supplements. Eds. P. Coates, M. Blackman, G. Cragg, M. Levine, J. Moss, and J. White (New York: Marcel Dekker), 545–553. doi: 10.1201/ b13959-57.
  • Simpson, T., Kure, C., & Stough, C. (2019). Assessing the Efficacy and Mechanisms of Pycnogenol® on Cognitive Aging From in Vitro Animal and Human Studies. Frontiers in Pharm, 10, 694.
  • Sharma, G., Tyagi, AK., Singh, RP., Chan, DC., & Agarwal, R. (2004). Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Research and Treatment, 85(1), 1-12.
  • Taner, G., Aydin, S., Aytac, Z., Basaran, AA., & Basaran, N. (2013). Assessment of the cytotoxic, genotoxic and antigenotoxic potential of Pycnogenol in in vitro mammalian cells. Food and Chemical Toxicology, 61, 203-208.
  • Taner, G., Aydin, S., Bacanli, M., Sarigol, Z., Sahin, T., Basaran, AA., & et al. (2014) Modulating effects of pycnogenol on oxidative stress and DNA damage induced by sepsis in rats. Phytotherapy Research, 28(11), 1692-700.
  • The American Botanical Council (2019). Scientific and clinical monograph for Pycnogenol (French maritime pine bark extract) Pinus pinaster Aiton subsp. atlantica [Fam. Pinaceae].
  • Yang, IH., Shin JA., Cho, SD. (2014). Pycnogenol Induces Nuclear Translocation of Apoptosisinducing Factor and Caspase-independent Apoptosis in MC-3 Human Mucoepidermoid Carcinoma Cell Line. Journal of Cancer Prevention, 19(4):265-72.
  • Yang, IH., Shin, JA., Kim, LH., Kwon, KH., & Cho, SD. (2016). The caspase 3-dependent apoptotic effect of pycnogenol in human oral squamous cell carcinoma HSC-3 cells. Journal of Clinical Biochemistry and Nutrition, 58(1), 40-7.
APA BECIT KIZILKAYA M, Aydin Dilsiz S, BAŞARAN N (2021). Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. , 13 - 22.
Chicago BECIT KIZILKAYA Merve,Aydin Dilsiz Sevtap,BAŞARAN NURŞEN Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. (2021): 13 - 22.
MLA BECIT KIZILKAYA Merve,Aydin Dilsiz Sevtap,BAŞARAN NURŞEN Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. , 2021, ss.13 - 22.
AMA BECIT KIZILKAYA M,Aydin Dilsiz S,BAŞARAN N Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. . 2021; 13 - 22.
Vancouver BECIT KIZILKAYA M,Aydin Dilsiz S,BAŞARAN N Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. . 2021; 13 - 22.
IEEE BECIT KIZILKAYA M,Aydin Dilsiz S,BAŞARAN N "Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability." , ss.13 - 22, 2021.
ISNAD BECIT KIZILKAYA, Merve vd. "Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability". (2021), 13-22.
APA BECIT KIZILKAYA M, Aydin Dilsiz S, BAŞARAN N (2021). Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. FABAD Journal of Pharmaceutical Sciences, 46(1), 13 - 22.
Chicago BECIT KIZILKAYA Merve,Aydin Dilsiz Sevtap,BAŞARAN NURŞEN Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. FABAD Journal of Pharmaceutical Sciences 46, no.1 (2021): 13 - 22.
MLA BECIT KIZILKAYA Merve,Aydin Dilsiz Sevtap,BAŞARAN NURŞEN Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. FABAD Journal of Pharmaceutical Sciences, vol.46, no.1, 2021, ss.13 - 22.
AMA BECIT KIZILKAYA M,Aydin Dilsiz S,BAŞARAN N Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. FABAD Journal of Pharmaceutical Sciences. 2021; 46(1): 13 - 22.
Vancouver BECIT KIZILKAYA M,Aydin Dilsiz S,BAŞARAN N Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability. FABAD Journal of Pharmaceutical Sciences. 2021; 46(1): 13 - 22.
IEEE BECIT KIZILKAYA M,Aydin Dilsiz S,BAŞARAN N "Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability." FABAD Journal of Pharmaceutical Sciences, 46, ss.13 - 22, 2021.
ISNAD BECIT KIZILKAYA, Merve vd. "Effects of Pycnogenol and Its Combinations with Cisplatin on Hepatocellular Carcinoma Cell Viability". FABAD Journal of Pharmaceutical Sciences 46/1 (2021), 13-22.