Antiproliferative Effect of Thymoquinone on Human Colon Cancer Cells: Is It Dependent on Glycolytic Pathway?

Mete Özkoç; Ergul Mutlu Altundag

doi:10.31067/acusaglik.1197182

EN

Antiproliferative Effect of Thymoquinone on Human Colon Cancer Cells: Is It Dependent on Glycolytic Pathway?

Abstract

ABSTRACT Purpose: In the present study, we aimed to investigate the anti-proliferative effect and metabolic activity of thymoquinone (TQ) on colon cancer cells (HCT-116). Material and Methods: Cell viability was determined by MTT analysis. Cells were treated with different concentrations of TQ (40, 60, 80, 100, 150, and 200 µM) on HCT-116 cells and half-maximal inhibitory concentration (IC50) values were calculated by using the CompuSyn software program. In addition, glucose and lactate concentrations were measured from cell culture supernatants for RPMI medium, control and TQ (IC50 dose) groups. Statistical analyses were performed using GraphPad Prism 7. Results: Thymoquinone was found to be antiproliferative particularly in 40-200 µM concentrations. The IC50 concentration of TQ was calculated as 68 µM. Glucose levels of supernatants were 478, 384±8.5 and 412±19.7 mg/dL in RPMI medium, control and TQ group, respectively. Lactate levels were found as 20±3.5 µM in the control group and 8±1.1 µM in TQ group. Conclusion: The present study showed that TQ has an antiproliferative effect on HCT-116 in addition to its inhibitory effect on a glycolytic pathway.

Keywords

References

1. Sinicrope FA. Increasing Incidence of Early-Onset Colorectal Cancer. New England Journal of Medicine. 2022;386:1547–1558. DOI:10.1056/nejmra2200869
2. Mármol I, Sánchez-de-Diego C, Dieste AP, et al. Colorectal carcinoma: A general overview and future perspectives in colorectal cancer. Vol. 18, International Journal of Molecular Sciences. MDPI AG; 2017. DOI:10.3390/ijms18010197
3. Mouradov D, Sloggett C, Jorissen RN, et al. Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer. Cancer Res. 2014;74:3238–3247. DOI:10.1158/0008-5472.CAN-14-0013
4. Markowitz SD and Bertagnolli MM. Molecular Basis of Colorectal Cancer. New England Journal of Medicine. 2009;361. DOI:10.1056/nejmra0804588
5. García-Alfonso P, Muñoz Martín AJ, Ortega Morán L, et al. Oral drugs in the treatment of metastatic colorectal cancer. Vol. 13, Therapeutic Advances in Medical Oncology. 2021. DOI:10.1177/17588359211009001
6. Huang X mei, Yang Z jie, Xie Q, et al. Natural products for treating colorectal cancer: A mechanistic review. Vol. 117, Biomedicine and Pharmacotherapy. 2019. DOI:10.1016/j.biopha.2019.109142
7. Ali BH and Blunden G. Pharmacological and toxicological properties of Nigella sativa. Vol. 17, Phytotherapy Research. 2003. DOI:10.1002/ptr.1309
8. Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, et al. Thymoquinone and its therapeutic potentials. Vols 95–96, Pharmacological Research. 2015. DOI:10.1016/j.phrs.2015.03.011

9. Fadaka A, Ajiboye B, Ojo O, et al. Biology of glucose metabolization in cancer cells. Journal of Oncological Sciences. 2017;3:45–51. DOI:10.1016/j.jons.2017.06.002
10. Biller LH and Schrag D. Diagnosis and treatment of metastatic colorectal cancer: A review. Vol. 325, JAMA - Journal of the American Medical Association. 2021. DOI:10.1001/jama.2021.0106
11. Nobili S, Lippi D, Witort E, et al. Natural compounds for cancer treatment and prevention. Pharmacol Res. 2009;59:365–378. DOI:10.1016/j.phrs.2009.01.017
12. Jafri SH, Glass J, Shi R, et al. Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo. Journal of Experimental and Clinical Cancer Research. 2010;29:1–11. DOI:10.1186/1756-9966-29-87
13. Imran M, Rauf A, Khan IA, et al. Thymoquinone: A novel strategy to combat cancer: A review. Biomedicine and Pharmacotherapy. 2018;106:390–402. DOI:10.1016/j.biopha.2018.06.159
14. Kundu J, Choi BY, Jeong CH, et al. Thymoquinone induces apoptosis in human colon cancer HCT-116 cells through inactivation of STAT3 by blocking JAK2- and Src-mediated phosphorylation of EGF receptor tyrosine kinase. Oncol Rep. 2014;32. DOI:10.3892/or.2014.3223
15. Gali-Muhtasib H, Diab-Assaf M, Boltze C, et al. Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol. 2004;25.
16. El-Far AH, Godugu K, Noreldin AE, et al. Thymoquinone and Costunolide Induce Apoptosis of Both Proliferative and Doxorubicin-Induced-Senescent Colon and Breast Cancer Cells. Integr Cancer Ther. 2021;20. DOI:10.1177/15347354211035450
17. Akram M. Mini-review on glycolysis and cancer. Vol. 28, Journal of Cancer Education. 2013. DOI:10.1007/s13187-013-0486-9
18. Lee YM, Kim GH, Park EJ, et al. Thymoquinone selectively kills hypoxic renal cancer cells by suppressing HIF‐1α‐mediated glycolysis. Int J Mol Sci. 2019;20. DOI:10.3390/ijms20051092
19. Karim S, Burzangi AS, Ahmad A, et al. PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer. Int J Mol Sci. 2022;23. DOI:10.3390/ijms23042305

Details

Primary Language

English

Subjects

Biochemistry and Cell Biology (Other)

Journal Section

Research Article

Authors

Mete Özkoç
0000-0003-3557-4349
Türkiye

Ergul Mutlu Altundag ^*
0000-0001-5355-4654
Kuzey Kıbrıs Türk Cumhuriyeti

Publication Date

March 17, 2023

Submission Date

November 2, 2022

Acceptance Date

February 19, 2023

Published in Issue

Year 2023 Volume: 14 Number: 2

DOI

https://doi.org/10.31067/acusaglik.1197182

IZ

https://izlik.org/JA84AH92PU

Cite

RIS / Bibtex

EndNote

Özkoç M, Mutlu Altundag E (March 1, 2023) Antiproliferative Effect of Thymoquinone on Human Colon Cancer Cells: Is It Dependent on Glycolytic Pathway? Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 14 2 103–107.

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