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Investigation of The Antiproliferative Effect of Colchicine on SNU-1 Gastric Cancer Cells

Year 2023, , 263 - 267, 30.06.2023

Fatih Yulak

https://doi.org/10.17776/csj.1256954

Abstract

In this study, colchicine's cytotoxic effects on SNU-1 cells were examined, and a probable mechanism behind its cytotoxicity was revealed. According to the results of the study, colchicine displayed considerable cytotoxicity with an IC50 value of 14.81ng/ml when it was administered to the cells for 24 hours at different doses ranging from 5 to 100ng/ml. Furthermore, according to mechanistic studies, usege of colchicine significantly increased both early and late apoptotic cells in flow cytometry experiments. The late apoptotic cell population percentage in the control group (5.14 ± 1.27%) dramatically increased to 22.83 ± 1.38% in 14.81ng/ml colchicine treated cells. The early apoptotic cell population percentage in the control group (2.00 ± 1.12%) increased to 6.57 ± 2.35% in 14.81ng/ml colchicine treated cells. ELISA method was used to evaluate how colchicine affects the expression of pro- and anti-apoptotic proteins in SNU-1 cells. Colchicine treatment increased pro-apoptotic Bax and cleaved caspase 3 activities, while anti-apoptotic BCL-2 levels decreased. It is concluded that colchicine increases apoptosis in SNU-1 cells, which leads to an overall increase in cell death. Colchicine's promise as an anticancer drug to treat stomach cancer, however, needs additional research to be determined.

Keywords

Gastric cancer Colchicine Antiproliferative effect Apoptozis.

Thanks

The author is grateful to the CÜTFAM research center that provided the infrastructure for the experiments.

References

  • [1] A. R. Yusefi, K. Bagheri Lankarani, P. Bastani, M. Radinmanesh, and Z. Kavosi, Risk Factors for Gastric Cancer: A Systematic Review, Asian Pac. J. Cancer Prev., 19(3) (2018) 591–603.
  • [2] J. Machlowska, J. Baj, M. Sitarz, R. Maciejewski, and R. Sitarz, Molecular Sciences Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies, International J. of Molecular Sciences, 21(11) (2020) 4012.
  • [3] J. Ferlay, H. R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, Estimates of worldwide burden of cancer in 2008, Int. J. Cancer, 127(12) (2010) 2893–2917.
  • [4] A. Jemal, M. M. Center, C. DeSantis, and E. M. Ward, Global patterns of cancer incidence and mortality rates and trends, Cancer Epidemiol. biomarkers Prev. a Publ. Am. Assoc. Cancer Res. cosponsored by Am. Soc. Prev. Oncol., 19(8) (2010) 1893–1907.
  • [5] X.-Y. Zhang, P.-Y. Zhang, Gastric cancer: somatic genetics as a guide to therapy., J. Med. Genet., 54(5) (2017) 305–312.
  • [6] J.-P. Gao, W. Xu, W.-T. Liu, M. Yan, and Z.-G. Zhu, Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell., World J. Gastroenterol., 24(24) (2018) 2567–2581.
  • [7] J. Y. Park, L. von Karsa, and R. Herrero, Prevention strategies for gastric cancer: a global perspective., Clin. Endosc., 47(6) (2014) 478–489.
  • [8] H. H. Hartgrink, E. P. M. Jansen, N. C. T. Van Grieken, and A. V. L. Hospital, HHS Public Access, 374(9688) (2015) 477–490.
  • [9] D. Roda, E. Rodrı, A. Cervantes, and S. Rosello, The treatment of advanced gastric cancer : current strategies and future perspectives, 19(Supplement 5) (2008) 103–107.
  • [10] H. Luo et al., Cetuximab enhances the effect of oxaliplatin on hypoxic gastric cancer cell lines, Oncology Reports, 23(6) (2010) 1735–1745.
  • [11] T. A. Bhat and R. P. Singh, Tumor angiogenesis - A potential target in cancer chemoprevention, Food Chem. Toxicol., 46(4) (2008) 1334–1345.
  • [12] S. Bhattacharya, A. Das, S. Datta, A. Ganguli, and G. Chakrabarti, Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy, Tumor Biol., 37(8) (2016) 10653–10664.
  • [13] Z. Huang, Y. Xu, and W. Peng, Colchicine induces apoptosis in HT-29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways, Mol. Med. Rep., 12(4) (2015) 5939–5944.
  • [14] I. Dudkiewicz, T. Brosh, M. Perelman, and M. Salai, Colchicine inhibits fracture union and reduces bone strength - In vivo study, J. Orthop. Res., 23(4) (2005) 877–881.
  • [15] Marshall M. Kaplan, Raoul Poupon, Treatment with immunosuppressives in patients with primary biliary cirrhosis who fail to respond to ursodiol, Hepatology, 50(2) (2009) 652.
  • [16] A. Kumar, B. Singh, P. R. Sharma, S. B. Bharate, A. K. Saxena, and D. M. Mondhe, A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT-116 colon cancer cells, Cell Biochem. Funct., 34(2) (2016) 69–81.
  • [17] G. C. Sun, H. H. Chen, W. Z. Liang, and C. R. Jan, Exploration of the effect of the alkaloid colchicine on Ca 2+ handling and its related physiology in human oral cancer cells, Arch. Oral Biol., 102(April) (2019) 179–185.
  • [18] A. Kumar, P. R. Sharma, and D. M. Mondhe, Potential anticancer role of colchicine-based derivatives: An overview, Anticancer. Drugs, 28(3) (2016) 250–262.
  • [19] J. Ferlay, H.-R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int. J. Cancer, 127(12) (2010) 2893–2917.
  • [20] J. P. Gao, W. Xu, W. T. Liu, M. Yan, and Z. G. Zhu, Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell, World J. Gastroenterol., 24(24) (2018) 2567–2581.
  • [21] O. Handa and Y. Naito, Prevention strategy for gastric cancer, Gastric Cancer With Spec. Focus Stud. from Japan, 1st ed. Japan, (2018) 193–201.
  • [22] M. A. Jordan and L. Wilson, “Microtubules and actin filaments: Dynamic targets for cancer chemotherapy, Curr. Opin. Cell Biol., 10(1) (1998) 123–130.
  • [23] M. A. Jordan and L. Wilson, Microtubules As a Target for Anticancer Drug, Nature Reviews Cancer, 4 (2004) 253-265.
  • [24] G. V Ronnett and C. Moon, G Proteins and Olfactory Signal Transduction, Annual Review of Physiology, 64(5) (2002) 189–222.
  • [25] E. K. Rowinsky and R. C. Donehower, The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics, Pharmacol. Ther., 52(1) (1991) 35–84.
  • [26] E. W. Taylor, The Mechanism of Colchicine Inhibition of Mitosis. I. Kinetics of Inhibition and the Binding of H3-Colchicine., J. Cell Biol., 25(1), (1965) 145–160.
  • [27] L. L. Fessler, Michael B.; Rudel, “基因的改变NIH Public Access, Bone, 23(1) (2011) 1–7.
  • [28] S. Bhattacharya, A. Das, S. Datta, A. Ganguli, and G. Chakrabarti, Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy, Tumor Biology, 37 (2016) 10653–10664
  • [29] Z. Y. Lin, C. C. Wu, Y. H. Chuang, and W. L. Chuang, Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma, Life Sci., 93(8) (2013) 323–328.
  • [30] X. Zhu et al., Osthole inhibits the PI3K/AKT signaling pathway via activation of PTEN and induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma, Biomed. Pharmacother., 102(november) (2018) 502–509.
  • [31] A. Maryam, T. Mehmood, Q. Yan, Y. Li, M. Khan, and T. Ma, Proscillaridin A promotes oxidative stress and ER stress, inhibits STAT3 activation, and induces apoptosis in A549 lung adenocarcinoma cells, Oxid. Med. Cell. Longev., 2018 (2018) 1-17.
  • [32] Z. Chen, B. Zhang, F. Gao, and R. Shi, Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts, Oncol. Lett., 15(2) (2018) 1559–1565.
  • [33] J. A. Hickman, Apoptosis and chemotherapy resistance, Eur. J. Cancer, 32(6) (1996) 921–926.
  • [34] B. A. Carneiro and W. S. El-Deiry, Targeting apoptosis in cancer therapy, Nat. Rev. Clin. Oncol., 17(7) (2020) 395–417.
  • [35] G. C. Cavalcante et al., A cell’s fate: An overview of the molecular biology and genetics of apoptosis, Int. J. Mol. Sci., 20(17) (2019) 1–20.
  • [36] F. Bakar-Ates, E. Ozkan, and C. T. Sengel-Turk, Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231 cells through PARP cleavage, Int. J. Pharm., 586(April) (2020) 119565.
  • [37] R. Jan and G.-S. Chaudhry, Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics, Adv Pharm Bull, 2019(2) (2019) 205–218.
  • [38] R. C. Wang et al., Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents, PLoS One, 12(8) (2017) 1–22.
  • [39] Q. Guo et al., Ligand- and structural-based discovery of potential small molecules that target the colchicine site of tubulin for cancer treatment, Eur. J. Med. Chem., 196 (2020) 112328.

Year 2023, , 263 - 267, 30.06.2023

Fatih Yulak

https://doi.org/10.17776/csj.1256954

Abstract

References

  • [1] A. R. Yusefi, K. Bagheri Lankarani, P. Bastani, M. Radinmanesh, and Z. Kavosi, Risk Factors for Gastric Cancer: A Systematic Review, Asian Pac. J. Cancer Prev., 19(3) (2018) 591–603.
  • [2] J. Machlowska, J. Baj, M. Sitarz, R. Maciejewski, and R. Sitarz, Molecular Sciences Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies, International J. of Molecular Sciences, 21(11) (2020) 4012.
  • [3] J. Ferlay, H. R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, Estimates of worldwide burden of cancer in 2008, Int. J. Cancer, 127(12) (2010) 2893–2917.
  • [4] A. Jemal, M. M. Center, C. DeSantis, and E. M. Ward, Global patterns of cancer incidence and mortality rates and trends, Cancer Epidemiol. biomarkers Prev. a Publ. Am. Assoc. Cancer Res. cosponsored by Am. Soc. Prev. Oncol., 19(8) (2010) 1893–1907.
  • [5] X.-Y. Zhang, P.-Y. Zhang, Gastric cancer: somatic genetics as a guide to therapy., J. Med. Genet., 54(5) (2017) 305–312.
  • [6] J.-P. Gao, W. Xu, W.-T. Liu, M. Yan, and Z.-G. Zhu, Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell., World J. Gastroenterol., 24(24) (2018) 2567–2581.
  • [7] J. Y. Park, L. von Karsa, and R. Herrero, Prevention strategies for gastric cancer: a global perspective., Clin. Endosc., 47(6) (2014) 478–489.
  • [8] H. H. Hartgrink, E. P. M. Jansen, N. C. T. Van Grieken, and A. V. L. Hospital, HHS Public Access, 374(9688) (2015) 477–490.
  • [9] D. Roda, E. Rodrı, A. Cervantes, and S. Rosello, The treatment of advanced gastric cancer : current strategies and future perspectives, 19(Supplement 5) (2008) 103–107.
  • [10] H. Luo et al., Cetuximab enhances the effect of oxaliplatin on hypoxic gastric cancer cell lines, Oncology Reports, 23(6) (2010) 1735–1745.
  • [11] T. A. Bhat and R. P. Singh, Tumor angiogenesis - A potential target in cancer chemoprevention, Food Chem. Toxicol., 46(4) (2008) 1334–1345.
  • [12] S. Bhattacharya, A. Das, S. Datta, A. Ganguli, and G. Chakrabarti, Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy, Tumor Biol., 37(8) (2016) 10653–10664.
  • [13] Z. Huang, Y. Xu, and W. Peng, Colchicine induces apoptosis in HT-29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways, Mol. Med. Rep., 12(4) (2015) 5939–5944.
  • [14] I. Dudkiewicz, T. Brosh, M. Perelman, and M. Salai, Colchicine inhibits fracture union and reduces bone strength - In vivo study, J. Orthop. Res., 23(4) (2005) 877–881.
  • [15] Marshall M. Kaplan, Raoul Poupon, Treatment with immunosuppressives in patients with primary biliary cirrhosis who fail to respond to ursodiol, Hepatology, 50(2) (2009) 652.
  • [16] A. Kumar, B. Singh, P. R. Sharma, S. B. Bharate, A. K. Saxena, and D. M. Mondhe, A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT-116 colon cancer cells, Cell Biochem. Funct., 34(2) (2016) 69–81.
  • [17] G. C. Sun, H. H. Chen, W. Z. Liang, and C. R. Jan, Exploration of the effect of the alkaloid colchicine on Ca 2+ handling and its related physiology in human oral cancer cells, Arch. Oral Biol., 102(April) (2019) 179–185.
  • [18] A. Kumar, P. R. Sharma, and D. M. Mondhe, Potential anticancer role of colchicine-based derivatives: An overview, Anticancer. Drugs, 28(3) (2016) 250–262.
  • [19] J. Ferlay, H.-R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int. J. Cancer, 127(12) (2010) 2893–2917.
  • [20] J. P. Gao, W. Xu, W. T. Liu, M. Yan, and Z. G. Zhu, Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell, World J. Gastroenterol., 24(24) (2018) 2567–2581.
  • [21] O. Handa and Y. Naito, Prevention strategy for gastric cancer, Gastric Cancer With Spec. Focus Stud. from Japan, 1st ed. Japan, (2018) 193–201.
  • [22] M. A. Jordan and L. Wilson, “Microtubules and actin filaments: Dynamic targets for cancer chemotherapy, Curr. Opin. Cell Biol., 10(1) (1998) 123–130.
  • [23] M. A. Jordan and L. Wilson, Microtubules As a Target for Anticancer Drug, Nature Reviews Cancer, 4 (2004) 253-265.
  • [24] G. V Ronnett and C. Moon, G Proteins and Olfactory Signal Transduction, Annual Review of Physiology, 64(5) (2002) 189–222.
  • [25] E. K. Rowinsky and R. C. Donehower, The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics, Pharmacol. Ther., 52(1) (1991) 35–84.
  • [26] E. W. Taylor, The Mechanism of Colchicine Inhibition of Mitosis. I. Kinetics of Inhibition and the Binding of H3-Colchicine., J. Cell Biol., 25(1), (1965) 145–160.
  • [27] L. L. Fessler, Michael B.; Rudel, “基因的改变NIH Public Access, Bone, 23(1) (2011) 1–7.
  • [28] S. Bhattacharya, A. Das, S. Datta, A. Ganguli, and G. Chakrabarti, Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy, Tumor Biology, 37 (2016) 10653–10664
  • [29] Z. Y. Lin, C. C. Wu, Y. H. Chuang, and W. L. Chuang, Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma, Life Sci., 93(8) (2013) 323–328.
  • [30] X. Zhu et al., Osthole inhibits the PI3K/AKT signaling pathway via activation of PTEN and induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma, Biomed. Pharmacother., 102(november) (2018) 502–509.
  • [31] A. Maryam, T. Mehmood, Q. Yan, Y. Li, M. Khan, and T. Ma, Proscillaridin A promotes oxidative stress and ER stress, inhibits STAT3 activation, and induces apoptosis in A549 lung adenocarcinoma cells, Oxid. Med. Cell. Longev., 2018 (2018) 1-17.
  • [32] Z. Chen, B. Zhang, F. Gao, and R. Shi, Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts, Oncol. Lett., 15(2) (2018) 1559–1565.
  • [33] J. A. Hickman, Apoptosis and chemotherapy resistance, Eur. J. Cancer, 32(6) (1996) 921–926.
  • [34] B. A. Carneiro and W. S. El-Deiry, Targeting apoptosis in cancer therapy, Nat. Rev. Clin. Oncol., 17(7) (2020) 395–417.
  • [35] G. C. Cavalcante et al., A cell’s fate: An overview of the molecular biology and genetics of apoptosis, Int. J. Mol. Sci., 20(17) (2019) 1–20.
  • [36] F. Bakar-Ates, E. Ozkan, and C. T. Sengel-Turk, Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231 cells through PARP cleavage, Int. J. Pharm., 586(April) (2020) 119565.
  • [37] R. Jan and G.-S. Chaudhry, Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics, Adv Pharm Bull, 2019(2) (2019) 205–218.
  • [38] R. C. Wang et al., Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents, PLoS One, 12(8) (2017) 1–22.
  • [39] Q. Guo et al., Ligand- and structural-based discovery of potential small molecules that target the colchicine site of tubulin for cancer treatment, Eur. J. Med. Chem., 196 (2020) 112328.
There are 39 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Natural Sciences
Authors

Fatih Yulak 0000-0003-3708-6752

Publication Date June 30, 2023
Submission Date February 27, 2023
Acceptance Date June 17, 2023
Published in Issue Year 2023

Cite

APA Yulak, F. (2023). Investigation of The Antiproliferative Effect of Colchicine on SNU-1 Gastric Cancer Cells. Cumhuriyet Science Journal, 44(2), 263-267. https://doi.org/10.17776/csj.1256954