SavedAdd your journal

Journals / Turkish Journal of Biology / 2018 / Cilt: 42 - Sayı: 3

Comparison of a ceramidase inhibitor (ceranib-2) with C2 ceramide and cisplatin on cytotoxicity and apoptosis of glioma cells

Gökhan KUŞ
Mete ÖZKURT
Pınar ÖZTOPCU VATAN
Ruhi UYAR
Selda KABADERE
Pages
259–265
Publication Date
2018-06-13
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

This cytotoxicity was stronger than that of C2 ceramide and cisplatin.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Inhibiting ceramidase activity in cancer cells has been identified as a promising target for cancer therapy in recent studies.
📊
Key Findings & Data:Thus, we examined the possible role of ceranib-2, a novel ceramidase inhibitor, on growth and apoptotic mechanisms of the human normal glia cell line (HNA), human glioma cell lines (T-98G and U-87MG), and a rat glioma cell line (C6).
💡
Conclusion & Impact:This cytotoxicity was stronger than that of C2 ceramide and cisplatin.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Ceranib-2 · C2 ceramide · cisplatin

Abstract

Inhibiting ceramidase activity in cancer cells has been identified as a promising target for cancer therapy in recent studies. Thus, we examined the possible role of ceranib-2, a novel ceramidase inhibitor, on growth and apoptotic mechanisms of the human normal glia cell line (HNA), human glioma cell lines (T-98G and U-87MG), and a rat glioma cell line (C6). We also compared the results with the effects of C2 ceramide and cisplatin. We determined the in vitro survival rate with MTT assay, apoptosis with flow cytometry, gene expressions with qRT-PCR, and statistical significance by one-way analysis of variance together with Tukey's test. Calculated from MTT outcomes, the inhibitory ranking was as follows: T-98G > U-87MG > C6 > HNA. Ceranib-2 had the most growth-suppressive activity on human T-98G cells with an IC50 of 7 μM for 24 h and 0.9 μM for 48 h. Only the 25 μM dose of ceranib-2 induced apoptosis of human T-98G and U-87MG cells after 24 h of treatment; however, it increased apoptosis of C6 cells dose- and time-dependently. Ceranib-2 increased the cytochrome c gene expression level during 24 h in T-98G cells. Ceranib-2 had cytotoxic and apoptotic effects on glioma cells but the cytotoxic effect was weaker on normal glia cells. This cytotoxicity was stronger than that of C2 ceramide and cisplatin.

🔖

Cite This Article

KUŞ, G., ÖZKURT, M., VATAN, P. Ö., UYAR, R., KABADERE, S. (2018). Comparison of a ceramidase inhibitor (ceranib-2) with C2 ceramide and cisplatin on cytotoxicity and apoptosis of glioma cells. Turkish Journal of Biology, Cilt: 42 - Sayı: 3, 259–265. https://ajindex.com/articles/181377

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (13)

  1. Draper JM, Xia Z, Smith RA, Zhuang Y, Wang W, Smith CD (2011). Discovery and evaluation of inhibitors of human ceramidase. Mol Cancer Ther 10: 2052-2061.
  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009). Cancer statistics, 2009. CA Cancer J Clin 59: 225-249.
  3. Gorojod RM, Alaimo A, Alcon SP, Saravia F, Kotler M L (2017). Interplay between lysosomal, mitochondrial and death receptor pathways during manganese-induced apoptosis in glial cells. Arc Toxicol 91: 3065-3078.
  4. Kim WH, Choi CH, Kang SK, Kwon CH, Kim YK (2005). Ceramide induces non-apoptotic cell death in human glioma cells. Neurochem Res 30: 969-979.
  5. Kus G, Kabadere S, Uyar R, Kutlu HM (2015). Induction of apoptosis in prostate cancer cells by the novel ceramidase inhibitor ceranib-2. In Vitro Cell & Dev Biol-An 51: 1056-1063.
  6. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63.
  7. Osawa Y, Uchinami H, Bielawski J, Schwabe RF, Hannun YA, Brenner DA (2005). Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte apoptosis in response to tumor necrosis factor-α. J Biol Chem 280: 27879-27887.
  8. Oskouian B, Saba JD (2010). Cancer treatment strategies targeting sphingolipid metabolism. Adv Exp Med Biol 688: 185-205.
  9. Oztopçu P, Kabadere S, Mercangöz A, Uyar R (2004). Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro. Acta Neurol Belg 104: 106-110.
  10. Park JB, Kim YB, Park EY (2015). Synergistic effect of nerve growth factor and insulin-like growth factor-1 on providing a pro- survival, anti-apoptotic benefit and increased extracellular matrix synthesis in stressed rat intervertebral disc cells. J Neurol Sci Turk 32: 728-737.
  11. Proksch D, Klein JJ, Arenz C (2011). Potent inhibition of acid ceramidase by novel B-13 analogues. J Lipids 2011: 971618. Realini N, Palese F, Pizzirani D, Pontis S, Basit A, Bach A, Ganesan A, Piomelli D (2016). Acid ceramidase in melanoma expression, localization, and effects of pharmacological inhibition. J Biol Chem 291: 2422-2434.
  12. Sawada M, Nakashima S, Banno Y, Yamakawa H, Hayashi K, Takenaka K, Nishimura Y, Sakai N, Nozawa Y (2000). Ordering of ceramide formation, caspase activation and Bax/Bcl-2 expression during etoposide-induced apoptosis in C6 glioma cells. Cell Death Differ 7: 761-772.
  13. Seelan RS, Qian C, Yokomizo A, Bostwick DG, Smith DI, Liu W (2000). Human acid ceramidase is overexpre