T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells

Ergül, Mustafa

doi:10.17776/csj.1238418

T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells

Mustafa ERGÜL (Sivas Cumhuriyet Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, Sivas, Türkiye)

Cumhuriyet Science Journal

3 0

Yıl: 2023 Cilt: 44 Sayı: 2 Sayfa Aralığı: 254 - 257 Metin Dili: İngilizce DOI: 10.17776/csj.1238418 İndeks Tarihi: 12-07-2023

T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells

Öz:

Accumulating evidence reports that T-type calcium channels play crucial roles in tumor formation and development. However, the roles of inhibiting calcium channels in tumor cells with various inhibitors in tumor progression remain unclear. This study aimed to investigate the cytotoxic and apoptotic effects of NNC 55-0396, a T-type calcium channel inhibitor, against SNU-1 gastric cancer cells. Cytotoxic and apoptotic effects of NNC 55-0396 were evaluated by the XTT assay and flow cytometry. The results showed that NNC 55-0396 had concentration-dependent cytotoxicity in SNU-1 cells and its the half-maximal inhibitory concentration (IC50) value was calculated as 4.17 µM. The results of the Annexin V experiments also showed that this inhibitor significantly increased apoptosis in SNU-1 cells. In conclusion, these results demonstrated that NNC 55-0396 induces cytotoxic effects by increasing apoptosis in gastric cancer cells. However, further research is required for its use as a possible therapeutic agent in the treatment of gastric cancer.

Anahtar Kelime: Gastric cancer NNC 55-0396 Cytotoxicity Apoptosis.

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

[1] Smyth E.C., Nilsson M., Grabsch H.I., van Grieken N.C., & Lordick F., Gastric cancer, Lancet (London, England), 396 (10251) (2020) 635–648.
[2] Karimi P., Islami F., Anandasabapathy S., Freedman N.D., & Kamangar F., Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention, Cancer Epidemiol Biomarkers Prev., 23 (5) (2014) 700–713.
[3] Joshi S.S., Badgwell B.D., Current treatment and recent progress in gastric cancer, CA Cancer J Clin., 71 (3) (2021) 264-279.
[4] Harada K., Sakamoto N., Ukai S., Yamamoto Y., Pham Q.T., Taniyama D., Honma R., Maruyama R., Takashima T., Ota H., Takemoto Y., Tanabe K., Ohdan H., & Yasui, W., Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance, Gastric Cancer, 24(6) (2021) 1264–1277.
[5] Gonçalves J.C.R., Coulidiati T.H., Monteiro A.L., Carvalho-Gonçalves L.C.T., Valença W.O., Oliveira R.N., Câmara C.A., Araújo D.A.M., Antitumoral activity of novel 1,4-naphthoquinonederivative involves L-type calcium channel activation in human colorectal cancer cell line, Journal of Applied Biomedicine, 14(3) (2016) 229-234.
[6] Monteith G.R., Davis F.M., Roberts-Thomson S.J., Calcium channels and pumps in cancer: changes and consequences, J. Biol. Chem., 287(38) (2012) 31666-31673.
[7] Wu L., Lin W., Liao Q., Wang H., Lin C., Tang L., Lian W., Chen Z., Li K., Xu L., Zhou R., Ding Y., & Zhao, L., Calcium Channel Blocker Nifedipine Suppresses Colorectal Cancer Progression and Immune Escape by Preventing NFAT2 Nuclear Translocation, Cell Reports, 33(4) (2020) 108327.
[8] Phan N.N., Wang C.Y., Chen C.F., Sun Z., Lai M.D., & Lin Y.C., Voltage-gated calcium channels: Novel targets for cancer therapy, Oncology Letters, 14(2) (2017) 2059–2074.
[9] Mason R.P., Calcium channel blockers, apoptosis and cancer: is there a biologic relationship?, Journal of the American College of Cardiology, 34(7) (1999) 1857–1866.
[10] Huang W., Lu C., Wu Y., Ouyang S., & Chen Y., T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell proliferation and induce cell apoptosis in leukemia cell lines, J. Exp. Clin. Cancer Res., 34(1) (2015) 54.
[11] Ergul M., Bakar-Ates F., A specific inhibitor of polo-like kinase 1, GSK461364A, suppresses proliferation of Raji Burkitt's lymphoma cells through mediating cell cycle arrest, DNA damage, and apoptosis, Chem Biol Interact., 332 (2020) 109288.
[12] Dziegielewska B., Gray L.S., Dziegielewski J., T-type calcium channels blockers as new tools in cancer therapies, Pflugers Arch., 466(4) (2014) 801-810.
[13] Nam Y., Ryu K.D., Jang C., Moon Y.H., Kim M., Ko D., Chung K.S., Gandini M.A., Lee K. T., Zamponi G.W., & Lee J.Y., Synthesis and cytotoxic effects of 2-thio-3,4-dihydroquinazoline derivatives as novel T-type calcium channel blockers, Bioorganic & Medicinal Chemistry, 28(11) (2020) 115491.
[14] Panner A., & Wurster R.D., T-type calcium channels and tumor proliferation, Cell Calcium, 40(2) (2006) 253–259.
[15] Das A., Pushparaj C., Herreros J., Nager M., Vilella R., Portero M., Pamplona R., Matias-Guiu X., Martí R.M., & Cantí C., T-type calcium channel blockers inhibit autophagy and promote apoptosis of malignant melanoma cells, Pigment cell & Melanoma Research, 26(6) (2013) 874–885.
[16] Valerie N.C., Dziegielewska B., Hosing A.S., Augustin E., Gray L.S., Brautigan D.L., Larner J.M., & Dziegielewski J., Inhibition of T-type calcium channels disrupts Akt signaling and promotes apoptosis in glioblastoma cells, Biochemical Pharmacology, 85(7) (2013) 888–897.
[17] Ohkubo T., & Yamazaki J., T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer cells, International Journal of Oncology, 41(1) (2012) 267–275.
[18] Granados K., Hüser L., Federico A., Sachindra S., Wolff G., Hielscher T., Novak D., Madrigal-Gambo, V., Sun Q., Vierthaler M., Larribère L., Umansky V., & Utikal J., T-type calcium channel inhibition restores sensitivity to MAPK inhibitors in de-differentiated and adaptive melanoma cells, British Journal of Cancer, 122(7) (2020) 1023–1036.

APA	Ergül M (2023). T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. , 254 - 257. 10.17776/csj.1238418
Chicago	Ergül Mustafa T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. (2023): 254 - 257. 10.17776/csj.1238418
MLA	Ergül Mustafa T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. , 2023, ss.254 - 257. 10.17776/csj.1238418
AMA	Ergül M T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. . 2023; 254 - 257. 10.17776/csj.1238418
Vancouver	Ergül M T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. . 2023; 254 - 257. 10.17776/csj.1238418
IEEE	Ergül M "T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells." , ss.254 - 257, 2023. 10.17776/csj.1238418
ISNAD	Ergül, Mustafa. "T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells". (2023), 254-257. https://doi.org/10.17776/csj.1238418

APA	Ergül M (2023). T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. Cumhuriyet Science Journal, 44(2), 254 - 257. 10.17776/csj.1238418
Chicago	Ergül Mustafa T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. Cumhuriyet Science Journal 44, no.2 (2023): 254 - 257. 10.17776/csj.1238418
MLA	Ergül Mustafa T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. Cumhuriyet Science Journal, vol.44, no.2, 2023, ss.254 - 257. 10.17776/csj.1238418
AMA	Ergül M T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. Cumhuriyet Science Journal. 2023; 44(2): 254 - 257. 10.17776/csj.1238418
Vancouver	Ergül M T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells. Cumhuriyet Science Journal. 2023; 44(2): 254 - 257. 10.17776/csj.1238418
IEEE	Ergül M "T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells." Cumhuriyet Science Journal, 44, ss.254 - 257, 2023. 10.17776/csj.1238418
ISNAD	Ergül, Mustafa. "T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells". Cumhuriyet Science Journal 44/2 (2023), 254-257. https://doi.org/10.17776/csj.1238418