Effect of Curcumin on the Head and Neck Squamous Cell Carcinoma Cell Line HN5

Article ID: e140422203601 Pages: 7

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Abstract

Background: Curcumin has been isolated from the rhizomes of Curcuma longa. Over the years, it has shown outstanding therapeutic potential in various human disorders, including cancers.

Objective: The aim is to study curcumin’s effects on the apoptosis signaling pathway in the head and neck squamous cell carcinoma (HNSCC) cell line HN5.

Methods: The cytotoxicity of curcumin on HN5 cells were assessed. In addition, HN5 cells were also treated with curcumin to evaluate its effect on the caspase-8, -9, Bcl-2, Bax, and Stat3 gene expressions.

Results: The results exhibited that cell viability reduced following curcumin treatment in a concentration- dependent manner. Curcumin treatment caused decreased expression of Bcl2, with simultaneous upregulation of the Bax/Bcl2 ratio. Curcumin increased caspase-9 expression, did not affect caspase-8, and decreased Stat3 expression. The induction of the mitochondria-dependent apoptosis pathway of curcumin happened by modulating the expression of Bcl2 and Bax genes, resulting in the caspase-9 activation. Furthermore, curcumin decreased the expression of the Stat3 in HN-5 cells.

Conclusions: In conclusion, curcumin showed marked anticancer effects in the HN-5 cell line by modulating Stat-3; Bax/Bcl-2 expression in vitro.

Keywords: Curcumin; HN5 cancer cell line, in vitro, molecular mechanism, Stat-3, Bax/Bcl-2, rhizomes.

Graphical Abstract

[1]
Sharifi, S.; Zununi Vahed, S.; Ahmadian, E.; Maleki Dizaj, S.; Abedi, A.; Hosseiniyan Khatibi, S.M.; Samiei, M. Stem cell therapy: Curcumin does the trick. Phytother. Res., 2019, 33(11), 2927-2937.
[http://dx.doi.org/10.1002/ptr.6482] [PMID: 31452263]
[2]
Sharifi, S.; Fathi, N.; Memar, M.Y.; Hosseiniyan Khatibi, S.M.; Khalilov, R.; Negahdari, R.; Zununi Vahed, S.; Maleki Dizaj, S. Anti-microbial activity of curcumin nanoformulations: New trends and future perspectives. Phytother. Res., 2020, 34(8), 1926-1946.
[http://dx.doi.org/10.1002/ptr.6658] [PMID: 32166813]
[3]
Negahdari, R.; Ghavimi, M.A.; Barzegar, A.; Memar, M.Y.; Balazadeh, L.; Bohlouli, S.; Sharifi, S.; Maleki Dizaj, S. Antibacterial effect of nanocurcumin inside the implant fixture: An in vitro study. Clin. Exp. Dent. Res., 2021, 7(2), 163-169.
[PMID: 33210463]
[4]
Ghavimi, M.A.; Bani Shahabadi, A.; Jarolmasjed, S.; Memar, M.Y.; Maleki Dizaj, S.; Sharifi, S. Nanofibrous asymmetric collagen/curcumin membrane containing aspirin-loaded PLGA nanoparticles for guided bone regeneration. Sci. Rep., 2020, 10(1), 18200.
[http://dx.doi.org/10.1038/s41598-020-75454-2] [PMID: 33097790]
[5]
Negahdari, R.; Sharifi, S.; Ghavimi, M.A.; Memar, M.Y.; Khaneshi, B.; Maleki Dizaj, S.; Eftekhari, A.; Cucchiarini, M. Curcumin nanocrystals: Production, physicochemical assessment, and in vitro evaluation of the antimicrobial effects against bacterial loading of the implant fixture. Appl. Sci. (Basel), 2020, 10, 8356.
[http://dx.doi.org/10.3390/app10238356]
[6]
Mantzorou, M.; Pavlidou, E.; Vasios, G.; Tsagalioti, E.; Giaginis, C. Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data. Phytother. Res., 2018, 32(6), 957-975.
[http://dx.doi.org/10.1002/ptr.6037] [PMID: 29468820]
[7]
Organization, W.H. Global action: Against cancer. , 2003; pp. 24-24.
[8]
Barone, D.; Cito, L.; Tommonaro, G.; Abate, A.A.; Penon, D.; De Prisco, R.; Penon, A.; Forte, I.M.; Benedetti, E.; Cimini, A.; Indovina, P.; Nicolaus, B.; Pentimalli, F.; Giordano, A. Antitumoral potential, antioxidant activity and carotenoid content of two Southern Italy tomato cultivars extracts. San Marzano and Corbarino. J. Cell. Physiol., 2018, 233(2), 1266-1277.
[http://dx.doi.org/10.1002/jcp.25995] [PMID: 28488765]
[9]
Bakhshaiesh, T.O.; Armat, M.; Shanehbandi, D.; Sharifi, S.; Baradaran, B.; Hejazi, M.S.; Samadi, N. Arsenic trioxide promotes paclitaxel cytotoxicity in resistant breast cancer cells. Asian Pac. J. Cancer Prev., 2015, 16(13), 5191-5197.
[http://dx.doi.org/10.7314/APJCP.2015.16.13.5191] [PMID: 26225652]
[10]
Mohseni, M.; Samadi, N.; Ghanbari, P.; Yousefi, B.; Tabasinezhad, M.; Sharifi, S.; Nazemiyeh, H. Co-treatment by docetaxel and vinblastine breaks down P-glycoprotein mediated chemo-resistance. Iran. J. Basic Med. Sci., 2016, 19(3), 300-309.
[PMID: 27114800]
[11]
Al-Ejeh, F.; Kumar, R.; Wiegmans, A.; Lakhani, S.R.; Brown, M.P.; Khanna, K.K. Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes. Oncogene, 2010, 29(46), 6085-6098.
[http://dx.doi.org/10.1038/onc.2010.407] [PMID: 20818418]
[12]
Giordano, A.; Tommonaro, G. Curcumin and Cancer. Nutrients, 2019, 11(10), 2376.
[http://dx.doi.org/10.3390/nu11102376] [PMID: 31590362]
[13]
Udagawa, T.; Wood, M. Tumor-stromal cell interactions and opportunities for therapeutic intervention. Curr. Opin. Pharmacol., 2010, 10(4), 369-374.
[http://dx.doi.org/10.1016/j.coph.2010.06.010] [PMID: 20638903]
[14]
Armat, M.; Oghabi Bakhshaiesh, T.; Sabzichi, M.; Shanehbandi, D.; Sharifi, S.; Molavi, O.; Mohammadian, J.; Saeid Hejazi, M.; Samadi, N. The role of Six1 signaling in paclitaxel-dependent apoptosis in MCF-7 cell line. Bosn. J. Basic Med. Sci., 2016, 16(1), 28-34.
[PMID: 26773176]
[15]
Samadi, N.; Ghanbari, P.; Mohseni, M.; Tabasinezhad, M.; Sharifi, S.; Nazemieh, H.; Rashidi, M.R. Combination therapy increases the efficacy of docetaxel, vinblastine and tamoxifen in cancer cells. J. Cancer Res. Ther., 2014, 10(3), 715-721.
[PMID: 25313766]
[16]
Bohlouli, S; Jafarmadar Gharehbagh, F; Dalir Abdolahinia, E; Kouhsoltani, M; Ebrahimi, G; Roshangar, L; Imani, A; Sharifi, S; Maleki Dizaj, S. Preparation, Characterization, and Evaluation of Rutin Nanocrystals as an Anticancer Agent against Head and Neck Squamous Cell Carcinoma Cell Line. Journal of Nanomaterials, 2021, 2021
[17]
Fisher, D.E. Apoptosis in cancer therapy: Crossing the threshold. Cell, 1994, 78(4), 539-542.
[http://dx.doi.org/10.1016/0092-8674(94)90518-5] [PMID: 8069905]
[18]
Debatin, K-M. Cytotoxic drugs, programmed cell death, and the immune system: Defining new roles in an old play; Oxford University Press, 1997.
[http://dx.doi.org/10.1093/jnci/89.11.750]
[19]
Green, D.R.; Reed, J.C. Mitochondria and apoptosis. Science, 1998, 1309-1312.
[20]
Rao, L.; White, E. Bcl-2 and the ICE family of apoptotic regulators: Making a connection. Curr. Opin. Genet. Dev., 1997, 7(1), 52-58.
[http://dx.doi.org/10.1016/S0959-437X(97)80109-8] [PMID: 9024635]
[21]
Gross, A. BCL-2 proteins: Regulators of the mitochondrial apoptotic program. IUBMB Life, 2001, 52(3-5), 231-236.
[http://dx.doi.org/10.1080/15216540152846046] [PMID: 11798037]
[22]
Huynh, H. Induction of apoptosis in rat ventral prostate by finasteride is associated with alteration in MAP kinase pathways and Bcl-2 related family of proteins. Int. J. Oncol., 2002, 20(6), 1297-1303.
[http://dx.doi.org/10.3892/ijo.20.6.1297] [PMID: 12012013]
[23]
Rossé, T.; Olivier, R.; Monney, L.; Rager, M.; Conus, S.; Fellay, I.; Jansen, B.; Borner, C. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature, 1998, 391(6666), 496-499.
[http://dx.doi.org/10.1038/35160] [PMID: 9461218]
[24]
Kagawa, S.; Pearson, S.A.; Ji, L.; Xu, K.; McDonnell, T.J.; Swisher, S.G.; Roth, J.A.; Fang, B. A binary adenoviral vector system for expressing high levels of the proapoptotic gene bax. Gene Ther., 2000, 7(1), 75-79.
[http://dx.doi.org/10.1038/sj.gt.3301048] [PMID: 10680019]
[25]
Kumar, S. Regulation of caspase activation in apoptosis: Implications in pathogenesis and treatment of disease. Clin. Exp. Pharmacol. Physiol., 1999, 26(4), 295-303.
[http://dx.doi.org/10.1046/j.1440-1681.1999.03031.x] [PMID: 10225139]
[26]
Ouyang, L.; Shi, Z.; Zhao, S.; Wang, F.T.; Zhou, T.T.; Liu, B.; Bao, J.K. Programmed cell death pathways in cancer: A review of apoptosis, autophagy and programmed necrosis. Cell Prolif., 2012, 45(6), 487-498.
[http://dx.doi.org/10.1111/j.1365-2184.2012.00845.x] [PMID: 23030059]
[27]
Jiang, S.; Gao, Y.; Hou, W.; Liu, R.; Qi, X.; Xu, X.; Li, J.; Bao, Y.; Zheng, H.; Hua, B. Sinomenine inhibits A549 human lung cancer cell invasion by mediating the STAT3 signaling pathway. Oncol. Lett., 2016, 12(2), 1380-1386.
[http://dx.doi.org/10.3892/ol.2016.4768] [PMID: 27446441]
[28]
Spitzner, M.; Ebner, R.; Wolff, H.A.; Ghadimi, B.M.; Wienands, J.; Grade, M. STAT3: A novel molecular mediator of resistance to chemoradiotherapy. Cancers (Basel), 2014, 6(4), 1986-2011.
[http://dx.doi.org/10.3390/cancers6041986] [PMID: 25268165]
[29]
Siveen, K.S.; Sikka, S.; Surana, R.; Dai, X.; Zhang, J.; Kumar, A.P.; Tan, B.K.; Sethi, G. Bishayee, A Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 2014, 1845, 136-154.
[http://dx.doi.org/10.1016/j.bbcan.2013.12.005]
[30]
Ishida, F.; Matsuda, K.; Sekiguchi, N.; Makishima, H.; Taira, C.; Momose, K.; Nishina, S.; Senoo, N.; Sakai, H.; Ito, T.; Kwong, Y.L. STAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia. Cancer Sci., 2014, 105(3), 342-346.
[http://dx.doi.org/10.1111/cas.12341] [PMID: 24350896]
[31]
Geletu, M.; Guy, S.; Raptis, L. Effects of SRC and STAT3 upon gap junctional, intercellular communication in lung cancer lines. Anticancer Res., 2013, 33(10), 4401-4410.
[PMID: 24123009]
[32]
Fathi, N.; Rashidi, G.; Khodadadi, A.; Shahi, S.; Sharifi, S. STAT3 and apoptosis challenges in cancer. Int. J. Biol. Macromol., 2018, 117, 993-1001.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.05.121] [PMID: 29782972]
[33]
Liu, Y.; Wang, X.; Zeng, S.; Zhang, X.; Zhao, J.; Zhang, X.; Chen, X.; Yang, W.; Yang, Y.; Dong, Z.; Zhu, J.; Xu, X.; Tian, F. The natural polyphenol curcumin induces apoptosis by suppressing STAT3 signaling in esophageal squamous cell carcinoma. J. Exp. Clin. Cancer Res., 2018, 37(1), 303.
[http://dx.doi.org/10.1186/s13046-018-0959-0] [PMID: 30518397]