Exploration of pro-apoptotic effect of Thymoquinone on oral squamous cell carcinoma cells through PI3K/Akt signaling pathway

Xun Ren; Wei Luo

doi:10.14715/cmb/2019.65.1.11

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Vol. 65 No. 1: Issue 1

Issue Published : February 4, 2019

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Exploration of pro-apoptotic effect of Thymoquinone on oral squamous cell carcinoma cells through PI3K/Akt signaling pathway

https://doi.org/10.14715/cmb/2019.65.1.11

Xun Ren

Department of Stomatology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, No.32, West Second Section, First Ring Road, Chengdu, Sichuan, China

Wei Luo

Department of Stomatology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, No.32, West Second Section, First Ring Road, Chengdu, Sichuan, China

Corresponding Author(s) : Wei Luo

zr12555@163.com

Cellular and Molecular Biology, Vol. 65 No. 1: Issue 1
Article Published : January 31, 2019

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer type in the world, with a 5-year survival rate of only 40% to 50%. Finding effective anti-tumor drug candidates is quite necessary for the progression of OSCC therapy. In this study, the role of Thymoquinone (TQ) in OSCC cells was studied. It was confirmed that TQ can inhibit the proliferation, migration and invasion of KB cells, and can also achieve apoptosis by inhibiting the activation of PI3K/Akt pathway. Therefore, TQ is an effective candidate for the treatment of OSCC.

Keywords

Thymoquinone Oral squamous cell carcinoma Pro-apoptotic PI3K-Akt.

Ren, X., & Luo, W. (2019). Exploration of pro-apoptotic effect of Thymoquinone on oral squamous cell carcinoma cells through PI3K/Akt signaling pathway. Cellular and Molecular Biology, 65(1), 61–64. https://doi.org/10.14715/cmb/2019.65.1.11

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References

Ragin CCR, Emanuela T. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 2010; 121: 1813-1820.
Ernani V, Saba NF. Oral Cavity Cancer: Risk Factors, Pathology, and Management. Oncol 2015; 89: 187.
Albuquerque R, López-López J, Marí-Roig A, Jané-Salas E, Roselló-Llabrés X, Santos JR. Oral tongue squamous cell carcinoma (OTSCC): alcohol and tobacco consumption versus non-consumption. A study in a Portuguese population. Braz Dent J 2011; 22: 517.
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Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral Oncol 2010; 46: 636-643.
Bredell M, Rordorf T, Studer G. Treatment concepts of oral cancer. SADJ 2012; 67: 574.
Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005; 99: 72-79100.
Fridlender M, Kapulnik Y, Koltai H. Plant derived substances with anti-cancer activity: from folklore to practice. Front Plant Sci 2015; 6: 799.
Vlachojannis C, Magora F, Chrubasik S. Rise and Fall of Oral Health Products with Canadian Bloodroot Extract. Phytother Res 2012; 26: 1423-1426.
Miller RA, Mciver JE, Gunsolley JC. Effects of sanguinaria extract on plaque retention and gingival health. J Clin Orthod 1988; 22: 304.
Galimuhtasib H, Diabassaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, 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: 857-866.
Galimuhtasib H, Roessner A, Schneiderstock R. Thymoquinone: a promising anti-cancer drug from natural sources. Int J Biochem Cell Biol 2006; 38: 1249-1253.
Ho HY, Ho YC, Hsieh MJ, Yang SF, Chuang CY, Lin CW, et al. Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma cells by inhibiting the urokinase-plasminogen activator through modulation of the Akt signaling pathway. Environ Toxicol 2016; 32: 645-655.
Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003; 9: 964-968.
Chen PN, Yang SF, Yu CC, Lin CY, Huang SH, Chu SC, et al. Duchesnea indica extract suppresses the migration of human lung adenocarcinoma cells by inhibiting epithelial-mesenchymal transition. Environ Toxicol 2017; 32: 2053-2063.
Lin CW, Yang WE, Lee WJ, Hua KT, Hsieh FK, Hsiao M, et al. Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis. Carcinogenesis 2016; 37: 712-722.
Su SC, Lin CW, Yang WE, Fan WL, Yang SF. The urokinase-type plasminogen activator (uPA) system as a biomarkerand therapeutic target in human malignancies. Expert Opin Ther Targets 2015; 20: 1.
Yeh CM, Su SC, Lin CW, Yang WE, Chien MH, Reiter RJ, et al. Melatonin as a potential inhibitory agent in head and neck cancer. Oncotarget 2017; 8: 90545-90556.
Hsin MC, Hsieh YH, Wang PH, Ko JL, Hsin IL, Yang SF. Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells. Cell Death Dis 2017; 8: 3089.
Awad ASM, Haleem ENAA, El-Bakly WM, Sherief MA. Thymoquinone alleviates nonalcoholic fatty liver disease in rats via suppression of oxidative stress, inflammation, apoptosis. Naunyn Schmiedebergs Arch Pharmacol 2016; 389: 381-391.
Heavey S, O'Byrne KJ, Gately K. Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC. Cancer Treatment Rev 2014; 40: 445-456.
Karar J, Maity A. PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci 2011; 4: 51.
Burris HA 3rd. Overcoming acquired resistance to anticancer therapy: focus on the; PI3K/AKT/mTOR pathway. Cancer Chemother Pharmacol 2013; 71: 829-842.
Molinolo AA, Amornphimoltham P, Squarize CH, Castilho RM, Patel V, Gutkind JS. Dysregulated molecular networks in Head & Neck carcinogenesis. Oral Oncol 2009; 45: 324-334.
Simpson DR, Mell LK, Cohen EE. Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol 2015; 51: 291-298.

References

Ragin CCR, Emanuela T. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 2010; 121: 1813-1820.

Ernani V, Saba NF. Oral Cavity Cancer: Risk Factors, Pathology, and Management. Oncol 2015; 89: 187.

Albuquerque R, López-López J, Marí-Roig A, Jané-Salas E, Roselló-Llabrés X, Santos JR. Oral tongue squamous cell carcinoma (OTSCC): alcohol and tobacco consumption versus non-consumption. A study in a Portuguese population. Braz Dent J 2011; 22: 517.

Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7: 169-181.

Bello IO, Soini Y, Salo T. Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II). Oral Oncol 2010; 46: 636-643.

Bredell M, Rordorf T, Studer G. Treatment concepts of oral cancer. SADJ 2012; 67: 574.

Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005; 99: 72-79100.

Fridlender M, Kapulnik Y, Koltai H. Plant derived substances with anti-cancer activity: from folklore to practice. Front Plant Sci 2015; 6: 799.

Vlachojannis C, Magora F, Chrubasik S. Rise and Fall of Oral Health Products with Canadian Bloodroot Extract. Phytother Res 2012; 26: 1423-1426.

Miller RA, Mciver JE, Gunsolley JC. Effects of sanguinaria extract on plaque retention and gingival health. J Clin Orthod 1988; 22: 304.

Galimuhtasib H, Diabassaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, 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: 857-866.

Galimuhtasib H, Roessner A, Schneiderstock R. Thymoquinone: a promising anti-cancer drug from natural sources. Int J Biochem Cell Biol 2006; 38: 1249-1253.

Ho HY, Ho YC, Hsieh MJ, Yang SF, Chuang CY, Lin CW, et al. Hispolon suppresses migration and invasion of human nasopharyngeal carcinoma cells by inhibiting the urokinase-plasminogen activator through modulation of the Akt signaling pathway. Environ Toxicol 2016; 32: 645-655.

Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, et al. BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 2003; 9: 964-968.

Chen PN, Yang SF, Yu CC, Lin CY, Huang SH, Chu SC, et al. Duchesnea indica extract suppresses the migration of human lung adenocarcinoma cells by inhibiting epithelial-mesenchymal transition. Environ Toxicol 2017; 32: 2053-2063.

Lin CW, Yang WE, Lee WJ, Hua KT, Hsieh FK, Hsiao M, et al. Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis. Carcinogenesis 2016; 37: 712-722.

Su SC, Lin CW, Yang WE, Fan WL, Yang SF. The urokinase-type plasminogen activator (uPA) system as a biomarkerand therapeutic target in human malignancies. Expert Opin Ther Targets 2015; 20: 1.

Yeh CM, Su SC, Lin CW, Yang WE, Chien MH, Reiter RJ, et al. Melatonin as a potential inhibitory agent in head and neck cancer. Oncotarget 2017; 8: 90545-90556.

Hsin MC, Hsieh YH, Wang PH, Ko JL, Hsin IL, Yang SF. Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells. Cell Death Dis 2017; 8: 3089.

Awad ASM, Haleem ENAA, El-Bakly WM, Sherief MA. Thymoquinone alleviates nonalcoholic fatty liver disease in rats via suppression of oxidative stress, inflammation, apoptosis. Naunyn Schmiedebergs Arch Pharmacol 2016; 389: 381-391.

Heavey S, O'Byrne KJ, Gately K. Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC. Cancer Treatment Rev 2014; 40: 445-456.

Karar J, Maity A. PI3K/AKT/mTOR Pathway in Angiogenesis. Front Mol Neurosci 2011; 4: 51.

Burris HA 3rd. Overcoming acquired resistance to anticancer therapy: focus on the; PI3K/AKT/mTOR pathway. Cancer Chemother Pharmacol 2013; 71: 829-842.

Molinolo AA, Amornphimoltham P, Squarize CH, Castilho RM, Patel V, Gutkind JS. Dysregulated molecular networks in Head & Neck carcinogenesis. Oral Oncol 2009; 45: 324-334.

Simpson DR, Mell LK, Cohen EE. Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol 2015; 51: 291-298.

Author biographies is not available.