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DOI: 10.1055/a-1700-4258
Investigating the Role of Thymoquinone in Increasing the Rate of Cisplatin-Induced Apoptosis through Oxidative DNA Damage in Saso-2 Cancer Cells
The Effect of TQ and Cis in OS
Abstract
Introduction Osteosarcoma (OS) is a primary bone sarcoma with a high recurrence rate and poorer prognosis. The application of natural agents in combinational therapies can increase the efficacy of treatment and decrease the side effects. Herein, we aimed to evaluate the effects of Thymoquinone (TQ) combined with Cisplatin on apoptosis and its underlying mechanisms in the Saos-2 cells.
Methods The effects of TQ and Cisplatin on Saos-2 cell viability were measured using an MTT assay. Western blotting was applied for the measurement of γH2AX protein expression. The expression levels of 8-Hydroxy-2'-deoxyguanosine (8-oxo-dG) were evaluated by enzyme-linked immunosorbent assay (ELISA). DCFH-DA fluorescence dye was used to detect reactive oxygen species (ROS) formation. For evaluation of apoptosis, flow cytometry was employed.
Results TQ dramatically promotes the cytotoxic effects of Cisplatin. TQ considerably enhanced the expression levels of 8-oxo-dG and γ-H2AX in Saos-2 cells. After TQ treatment, ROS levels were increased; furthermore, TQ treatment resulted in the potentiation of Cisplatin-induced apoptosis in Saos-2 cells compared to either TQ or Cisplatin treated cells.
Conclusion In general, TQ plus Cisplatin resulted in potentiated cellular cytotoxicity by increasing ROS level and inducing oxidative DNA damage, leading to the potent induction of apoptosis in tumor cells.
Publication History
Received: 24 August 2021
Accepted: 16 November 2021
Article published online:
07 March 2022
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References
- 1 Bazavar M, Fazar J, Valizadeh A. et al. miR-192 enhances sensitivity of methotrexate drug to MG-63 osteosarcoma cancer cells. Pathol Res Pract 2020; 216: 153176 doi: 10.1016/j.prp.2020.153176
- 2 Kansara M, Teng WM, Smyth JM. et al. Translational biology of osteosarcoma. Nat Rev Cancer 2014; 14: 722-735
- 3 Zvi Y, Ugur E, Batko B. et al. Prognostic and Therapeutic Utility of Variably Expressed Cell Surface Receptors in Osteosarcoma. Sarcoma 2021; 2021: 8324348
- 4 Lamhamedi-Cherradi SE, Mohiuddin S, Mishra KD. et al. Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma. Cancer Gene Ther 2021; 28: 1325-1338
- 5 Zheng D, Liu W, Xie W. et al. AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma. Signal Transduct Target Ther 2021; 6 25 doi:
- 6 Smrke A, Anderson MP, Gulia A. et al. Future Directions in the Treatment of Osteosarcoma. Cells 2021; 10 172 doi:
- 7 Wang G, Reed E, Li QQ. Molecular basis of cellular response to cisplatin chemotherapy in non-small cell lung cancer (Review). Oncol Rep 2004; 12 955-965
- 8 Oiso S, Ikeda R, Nakamura K. et al. Involvement of NF-κB activation in the cisplatin resistance of human epidermoid carcinoma KCP-4 cells. Oncol Rep 2012; 28: 27-32
- 9 Heneghan HM, Miller N, Lowery AJ. et al. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 2010; 251: 499-505
- 10 Lagunas VM, Meléndez-Zajgla J. Nuclear Factor-kappa B as a Resistance Factor to Platinum-Based Antineoplasic Drugs. Met Based Drugs 2008; 2008 576104
- 11 Srinivas US, Tan BWQ, Vellayappan BA. et al. ROS and the DNA damage response in cancer. Redox biology 2019; 25 p101084 doi: 10.1016/j.redox.2018.101084
- 12 Maleki M, Khelgati N, Alemi F. et al. Stabilization of telomere by the antioxidant property of polyphenols: Anti-aging potential. Life Sci 2020; 259: 118341
- 13 Imran M, Rauf A, Khan IA. et al. Thymoquinone: A novel strategy to combat cancer: A review. Biomed Pharmacother 2018; 106: 390-402
- 14 Mostofa AGM, Hossain K, Basak D. et al. Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies. Front Pharmacol 2017; 8: 295
- 15 van As JW, van den Berg H, van Dalen EC. Medical interventions for the prevention of platinum-induced hearing loss in children with cancer. Cochrane Database Syst Rev 2019; 5 Cd009219
- 16 Peng L, Liu A, Shen Y. et al. Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway. Oncol Rep 2013; 29: 571-578
- 17 Alaufi OM, Noorwali A, Zahran F. et al. Cytotoxicity of thymoquinone alone or in combination with cisplatin (CDDP) against oral squamous cell carcinoma in vitro. Sci Rep 2017; 7: 13131
- 18 Abdelfadil E, Cheng YH, Bau DT. et al. Thymoquinone induces apoptosis in oral cancer cells through p38β inhibition. Am J Chin Med 2013; 41: 683-696
- 19 Khan MA. et al. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med 2011; 8: 226-232
- 20 Zhang L, Bai Y, Yang Y. Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. Oncol Lett 2016; 12 2840-2845
- 21 Jafri SH, Glass J, Shi R. et al. Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo. J Exp Clin Cancer Res 2010; 29: 87
- 22 Ock C-Y. et al. 8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases. World journal of gastroenterology: WJG 2012; 18: 302
- 23 Sadoughi F, Hallajzadeh J, Asemi Z. et al. Signaling pathways involved in cell cycle arrest during the DNA breaks. DNA Repair (Amst) 2021; 98: 103047
- 24 Lin S, Li Y, Zamyatnin A. et al. Reactive oxygen species and colorectal cancer. J Cell Physiol 2018; 233: 5119-5132
- 25 Huang T, Zhou F, Yuan Y. et al. Reactive oxygen species are involved in the development of gastric cancer and gastric cancer-related depression through abl1-mediated inflammation signaling pathway. Oxid Med Cell Longev 2019: 2019; 5813985 doi:
- 26 Guo C, Li X, Wang R. et al. Association between oxidative DNA damage and risk of colorectal cancer: sensitive determination of urinary 8-hydroxy-2′-deoxyguanosine by UPLC-MS/MS analysis. Sci Rep 2016; 6: 32581. doi:
- 27 Roepke M, Diestel A, Bajbouj K. et al. Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol Ther 2007; 6: 160-169
- 28 Huang X. et al. Activation of ATM and histone H2AX phosphorylation induced by mitoxantrone but not by topotecan is prevented by the antioxidant N-acetyl-L-cysteine. Cancer biology & therapy 2006; 5: 959-964
- 29 Ikeda M, Kurose A, Takatori E. et al. DNA damage detected with γH2AX in endometrioid adenocarcinoma cell lines. Int J Oncol 2010; 36: 1081-1088