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Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway

  • Authors:
    • Ben Liu
    • Hui Wang
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    Affiliations: Department of Oncology, Shuyang County Hospital of Traditional Chinese Medicine, Suqian, Jiangsu 223600, P.R. China, Department of Oncology, The Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215004, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 394
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    Published online on: April 13, 2022
       https://doi.org/10.3892/etm.2022.11321
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Abstract

Oxaliplatin is a third‑generation platinum drug that is used as first‑line chemotherapy for colorectal cancer (CRC). Ferroptosis has been demonstrated to induce cell death and oxidative stress in CRC. The aim of the present study was to investigate whether oxaliplatin could exert anticancer effects on CRC by promoting ferroptosis and oxidative stress. Cell viability and apoptosis were assessed by performing Cell Counting Kit‑8 and TUNEL assays, respectively, in the presence or absence of the ferroptosis inducer, erastin. Western blotting was performed to detect the levels of certain nuclear factor erythroid 2‑related factor 2 (Nrf2)‑associated proteins in HT29 cells treated with oxaliplatin. Furthermore, after treating cells with the Nrf2 activator, NK‑252, Fe2+ was detected in cells using a commercial kit. Ferroptosis‑associated protein expression was also evaluated via western blotting. Additionally, ELISA was adopted to measure the levels of oxidative stress‑related factors. Following the addition of erastin, iron ion content, ferroptosis‑related protein expression and the levels of oxidative stress‑related factors were assayed as described previously. The results of the present study demonstrated that oxaliplatin inhibited viability and the Nrf2 signaling pathway in CRC cells. In addition, oxaliplatin promoted ferroptosis and oxidative stress in CRC cells by inhibiting the Nrf2 signaling pathway. Treatment with oxaliplatin enhanced the effects of erastin on CRC cells by promoting ferroptosis and oxidative stress and inhibiting cell viability. In conclusion, oxaliplatin induced ferroptosis and oxidative stress in CRC cells by inhibiting the Nrf2 signaling pathway.
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1 

Weitz J, Koch M, Debus J, Höhler T, Galle PR and Büchler MW: Colorectal cancer. Lancet. 365:153–165. 2005.PubMed/NCBI View Article : Google Scholar

2 

Pilonis ND, Bugajski M, Wieszczy P, Franczyk R, Didkowska J, Wojciechowska U, Pisera M, Rupinski M, Regula J and Kaminski MF: Long-term colorectal cancer incidence and mortality after a single negative screening colonoscopy. Ann Intern Med. 173:81–91. 2020.PubMed/NCBI View Article : Google Scholar

3 

Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ and Watanabe T: Colorectal cancer. Nat Rev Dis Primers. 1(15065)2015.PubMed/NCBI View Article : Google Scholar

4 

Binefa G, Rodríguez-Moranta F, Teule A and Medina-Hayas M: Colorectal cancer: From prevention to personalized medicine. World J Gastroenterol. 20:6786–6808. 2014.PubMed/NCBI View Article : Google Scholar

5 

Hsu HH, Chen MC, Baskaran R, Lin YM, Day CH, Lin YJ, Tu CC, Vijaya Padma V, Kuo WW and Huang CY: Oxaliplatin resistance in colorectal cancer cells is mediated via activation of ABCG2 to alleviate ER stress induced apoptosis. J Cell Physiol. 233:5458–5467. 2018.PubMed/NCBI View Article : Google Scholar

6 

Arango D, Wilson AJ, Shi Q, Corner GA, Arañes MJ, Nicholas C, Lesser M, Mariadason JM and Augenlicht LH: Molecular mechanisms of action and prediction of response to oxaliplatin in colorectal cancer cells. Br J Cancer. 91:1931–1946. 2004.PubMed/NCBI View Article : Google Scholar

7 

Sun X, Wang X, Feng W, Guo H, Tang C, Lu Y, Xiang X and Bao Y: Gene signatures associated with drug resistance to irinotecan and oxaliplatin predict a poor prognosis in patients with colorectal cancer. Oncol Lett. 13:2089–2096. 2017.PubMed/NCBI View Article : Google Scholar

8 

Zhang F, Li F, Lu GH, Nie W, Zhang L, Lv Y, Bao W, Gao X, Wei W, Pu K and Xie HY: Engineering magnetosomes for ferroptosis/immunomodulation synergism in cancer. ACS Nano. 13:5662–5673. 2019.PubMed/NCBI View Article : Google Scholar

9 

Zou Y, Palte MJ, Deik AA, Li H, Eaton JK, Wang W, Tseng YY, Deasy R, Kost-Alimova M, Dančík V, et al: A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat Commun. 10(1617)2019.PubMed/NCBI View Article : Google Scholar

10 

Shin D, Kim EH, Lee J and Roh JL: Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic Biol Med. 129:454–462. 2018.PubMed/NCBI View Article : Google Scholar

11 

Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ, Zoncu R, et al: The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 575:688–692. 2019.PubMed/NCBI View Article : Google Scholar

12 

Sang M, Luo R, Bai Y, Dou J, Zhang Z, Liu F, Feng F, Xu J and Liu W: Mitochondrial membrane anchored photosensitive nano-device for lipid hydroperoxides burst and inducing ferroptosis to surmount therapy-resistant cancer. Theranostics. 9:6209–6223. 2019.PubMed/NCBI View Article : Google Scholar

13 

Sui X, Zhang R, Liu S, Duan T, Zhai L, Zhang M, Han X, Xiang Y, Huang X, Lin H and Xie T: RSL3 drives ferroptosis through GPX4 inactivation and ROS production in colorectal cancer. Front Pharmacol. 9(1371)2018.PubMed/NCBI View Article : Google Scholar

14 

Lu Y, Wu S, Xiang B, Li L and Lin Y: Curcumin attenuates oxaliplatin-induced liver injury and oxidative stress by activating the Nrf2 pathway. Drug Des Devel Ther. 14:73–85. 2020.PubMed/NCBI View Article : Google Scholar

15 

Chian S, Li YY, Wang XJ and Tang XW: Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway. Asian Pac J Cancer Prev. 15:2911–2916. 2014.PubMed/NCBI View Article : Google Scholar

16 

Sun X, Ou Z, Chen R, Niu X, Chen D, Kang R and Tang D: Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology. 63:173–184. 2016.PubMed/NCBI View Article : Google Scholar

17 

Dodson M, Castro-Portuguez R and Zhang DD: NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol. 23(101107)2019.PubMed/NCBI View Article : Google Scholar

18 

Singh R, Zorrón Cheng Tao Pu L, Koay D and Burt A: Sessile serrated adenoma/polyps: Where are we at in 2016? World J Gastroenterol. 22:7754–7759. 2016.PubMed/NCBI View Article : Google Scholar

19 

Xiao ZM, Wang AM, Wang XY and Shen SR: Effects of ethanol extract of radix sophorae flavescentis on activity of colon cancer HT29 cells. Afr J Tradit Complement Altern Med. 10:352–355. 2013.PubMed/NCBI View Article : Google Scholar

20 

Przygodzka P, Papiewska-Pająk I, Bogusz-Koziarska H, Sochacka E, Boncela J and Kowalska MA: Regulation of miRNAs by Snail during epithelial-to-mesenchymal transition in HT29 colon cancer cells. Sci Rep. 9(2165)2019.PubMed/NCBI View Article : Google Scholar

21 

Mittag A, Schneider T, Westermann M and Glei M: Toxicological assessment of magnesium oxide nanoparticles in HT29 intestinal cells. Arch Toxicol. 93:1491–1500. 2019.PubMed/NCBI View Article : Google Scholar

22 

Riddell IA: Cisplatin and oxaliplatin: Our current understanding of their actions. Met Ions Life Sci. 18:2018.PubMed/NCBI View Article : Google Scholar

23 

Wang W, Wang M, Xu J, Long F and Zhan X: Overexpressed GATA3 enhances the sensitivity of colorectal cancer cells to oxaliplatin through regulating MiR-29b. Cancer Cell Int. 20(339)2020.PubMed/NCBI View Article : Google Scholar

24 

Limagne E, Thibaudin M, Nuttin L, Spill A, Derangère V, Fumet JD, Amellal N, Peranzoni E, Cattan V and Ghiringhelli F: Trifluridine/tipiracil plus oxaliplatin improves PD-1 blockade in colorectal cancer by inducing immunogenic cell death and depleting macrophages. Cancer Immunol Res. 7:1958–1969. 2019.PubMed/NCBI View Article : Google Scholar

25 

Pirpour Tazehkand A, Akbarzadeh M, Velaie K, Sadeghi MR and Samadi N: The role of Her2-Nrf2 axis in induction of oxaliplatin resistance in colon cancer cells. Biomed Pharmacother. 103:755–766. 2018.PubMed/NCBI View Article : Google Scholar

26 

Yang C, Zhang Y, Lin S, Liu Y and Li W: Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. Aging (Albany NY). 13:13515–13534. 2021.PubMed/NCBI View Article : Google Scholar

27 

Zhu T, Shi L, Yu C, Dong Y, Qiu F, Shen L, Qian Q, Zhou G and Zhu X: Ferroptosis promotes photodynamic therapy: Supramolecular photosensitizer-inducer nanodrug for enhanced cancer treatment. Theranostics. 9:3293–3307. 2019.PubMed/NCBI View Article : Google Scholar

28 

Roh JL, Kim EH, Jang H and Shin D: Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol. 11:254–262. 2017.PubMed/NCBI View Article : Google Scholar

29 

Shi Y, Wang Y, Huang W, Wang Y, Wang R and Yuan Y: Integration of metabolomics and transcriptomics to reveal metabolic characteristics and key targets associated with cisplatin resistance in nonsmall cell lung cancer. J Proteome Res. 18:3259–3267. 2019.PubMed/NCBI View Article : Google Scholar

30 

Zhu J, Xiong Y, Zhang Y, Wen J, Cai N, Cheng K, Liang H and Zhang W: The molecular mechanisms of regulating oxidative stress-induced ferroptosis and therapeutic strategy in tumors. Oxid Med Cell Longev. 2020(8810785)2020.PubMed/NCBI View Article : Google Scholar

31 

Basak D, Uddin MN and Hancock J: The role of oxidative stress and its counteractive utility in colorectal cancer (CRC). Cancers (Basel). 12(3336)2020.PubMed/NCBI View Article : Google Scholar

32 

Shen LD, Qi WH, Bai JJ, Zuo CY, Bai DL, Gao WD, Zong XL, Hao TT, Ma Y and Cao GC: Resibufogenin inhibited colorectal cancer cell growth and tumorigenesis through triggering ferroptosis and ROS production mediated by GPX4 inactivation. Anat Rec (Hoboken). 304:313–322. 2021.PubMed/NCBI View Article : Google Scholar

33 

Wang J, Sun Y, Zhang X, Cai H, Zhang C, Qu H, Liu L, Zhang M, Fu J, Zhang J, et al: Oxidative stress activates NORAD expression by H3K27ac and promotes oxaliplatin resistance in gastric cancer by enhancing autophagy flux via targeting the miR-433-3p. Cell Death Dis. 12(90)2021.PubMed/NCBI View Article : Google Scholar

34 

Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS and Stockwell BR: Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 3(e02523)2014.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Liu B and Wang H: Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway. Exp Ther Med 23: 394, 2022.
APA
Liu, B., & Wang, H. (2022). Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway. Experimental and Therapeutic Medicine, 23, 394. https://doi.org/10.3892/etm.2022.11321
MLA
Liu, B., Wang, H."Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 23.6 (2022): 394.
Chicago
Liu, B., Wang, H."Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 23, no. 6 (2022): 394. https://doi.org/10.3892/etm.2022.11321
Copy and paste a formatted citation
x
Spandidos Publications style
Liu B and Wang H: Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway. Exp Ther Med 23: 394, 2022.
APA
Liu, B., & Wang, H. (2022). Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway. Experimental and Therapeutic Medicine, 23, 394. https://doi.org/10.3892/etm.2022.11321
MLA
Liu, B., Wang, H."Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 23.6 (2022): 394.
Chicago
Liu, B., Wang, H."Oxaliplatin induces ferroptosis and oxidative stress in HT29 colorectal cancer cells by inhibiting the Nrf2 signaling pathway". Experimental and Therapeutic Medicine 23, no. 6 (2022): 394. https://doi.org/10.3892/etm.2022.11321
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