Zinc finger domain of p62/SQSTM1 is involved in the necroptosis of human cisplatin‑resistant ovarian cancer cells treated with sulfasalazine

Liu,Nannan; Liu,Shanshan; Zhang,Xueshuang; Tian,Wenzhu; Jia,Heqiang; Ye,Xin; Yan,Xiaoyu; Yu,Chunyan; Yu,Huimei

doi:10.3892/ol.2024.14662

Zinc finger domain of p62/SQSTM1 is involved in the necroptosis of human cisplatin‑resistant ovarian cancer cells treated with sulfasalazine

Authors:
- Nannan Liu
- Shanshan Liu
- Xueshuang Zhang
- Wenzhu Tian
- Heqiang Jia
- Xin Ye
- Xiaoyu Yan
- Chunyan Yu
- Huimei Yu
View Affiliations

Affiliations: Department of Pathology, College of Basic Medicine, Beihua University, Jilin, Jilin 132013, P.R. China, Department of Transplantation, Hebei Yanda Ludaopei Hospital, Langfang, Hebei 065200, P.R. China, Department of Hematology, Changchun Central Hospital, Changchun, Jilin 130041, P.R. China, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: September 3, 2024 https://doi.org/10.3892/ol.2024.14662
Article Number: 529

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cisplatin resistance in ovarian cancer cells is mainly apoptosis resistant. Although other types of programmed cell death are highly involved in chemoresistance, which type can overcome cisplatin resistance remains unclear. The present study observed that cisplatin‑sensitive SKOV3 cells and cisplatin‑resistant SKOV3/DDP cells had different levels of sensitivity to sulfasalazine (SAS). The present study aimed to investigate the effect of SAS on necroptosis under the same inhibition rate in these two types of cells. Necroptosis inhibitor Necrostatin‑1 (Nec‑1) attenuated SAS‑induced SKOV3/DDP cytotoxicity. SAS decreased SKOV3/DDP cells survival rate, accompanied by decreased cell adhesion and spreading. SAS treatment activated necrosome formation in SKOV3/DDP cells, suggesting the possibility of necroptosis. p62/sequestosome‑1 (SQSTM1) protein expression levels were also increased over the same time period. The transfection of small interfering (si)‑p62 could decrease the ratios of phosphorylated (p)‑receptor‑interacting serine/threonine kinase 1 (RIP1)/RIP1, p‑receptor‑interacting serine/threonine kinase 3 (RIP3)/RIP3 and p‑mixed lineage kinase domain‑like protein (MLKL)/MLKL proteins in SKOV3/DDP cells. Under the si‑p62 condition, there was no increase in the rate of cell survival in Nec‑1 and SAS combination group compared with SAS. The zinc finger domain deletion of p62/SQSTM1 effectively decreased the expression levels of necroptosis‑related p‑proteins. Collectively, certain drugs were able to induce necroptosis in SKOV3/DDP, while p62/RIP1/RIP3/MLKL was associated with the induction of necroptosis and with increasing the sensitivity of cisplatin‑resistant ovarian cancer cells, which provided evidence for potential as a therapeutic target for overcoming resistance.

View Figures

View References

1	Zhang C and Liu N: Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer. Front Immunol. 13:9200592022. View Article : Google Scholar : PubMed/NCBI
2	Xu Y, Lin Z, Zhao N, Zhou L, Liu F, Cichacz Z, Zhang L, Zhan Q and Zhao X: Receptor interactive protein kinase 3 promotes Cisplatin-triggered necrosis in apoptosis-resistant esophageal squamous cell carcinoma cells. PLoS One. 9:e1001272014. View Article : Google Scholar : PubMed/NCBI
3	Zhang Y, Su SS, Zhao S, Yang Z, Zhong CQ, Chen X, Cai Q, Yang ZH, Huang D, Wu R and Han J: RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun. 8:143292017. View Article : Google Scholar : PubMed/NCBI
4	Schenk B and Fulda S: Reactive oxygen species regulate Smac mimetic/TNFα-induced necroptotic signaling and cell death. Oncogene. 34:5796–5806. 2015. View Article : Google Scholar : PubMed/NCBI
5	Hsu SK, Chang WT, Lin IL, Chen YF, Padalwar NB, Cheng KC, Teng YN, Wang CH and Chiu CC: The role of necroptosis in ROS-Mediated cancer therapies and its promising applications. Cancers (Basel). 12:21852020. View Article : Google Scholar : PubMed/NCBI
6	Shindo R, Kakehashi H, Okumura K, Kumagai Y and Nakano H: Critical contribution of oxidative stress to TNFα-induced necroptosis downstream of RIPK1 activation. Biochem Biophys Res Commun. 436:212–216. 2013. View Article : Google Scholar : PubMed/NCBI
7	Narang VS, Pauletti GM, Gout PW, Buckley DJ and Buckley AR: Suppression of cystine uptake by sulfasalazine inhibits proliferation of human mammary carcinoma cells. Anticancer Res. 23:4571–4579. 2003.PubMed/NCBI
8	Ji X, Qian J, Rahman SMJ, Siska PJ, Zou Y, Harris BK, Hoeksema MD, Trenary IA, Heidi C, Eisenberg R, et al: xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression. Oncogene. 37:5007–5019. 2018. View Article : Google Scholar : PubMed/NCBI
9	Guo W, Zhao Y, Zhang Z, Tan N, Zhao F, Ge C, Liang L, Jia D, Chen T, Yao M, et al: Disruption of xCT inhibits cell growth via the ROS/autophagy pathway in hepatocellular carcinoma. Cancer Lett. 312:55–61. 2011. View Article : Google Scholar : PubMed/NCBI
10	Jovanović L, Nikolić A, Dragičević S, Jović M and Janković R: Prognostic relevance of autophagy-related markers p62, LC3, and Beclin1 in ovarian cancer. Croat Med J. 63:453–460. 2022. View Article : Google Scholar : PubMed/NCBI
11	Adams O, Dislich B, Berezowska S, Schläfli AM, Seiler CA, Kröll D, Tschan MP and Langer R: Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas. Oncotarget. 7:39241–39255. 2016. View Article : Google Scholar : PubMed/NCBI
12	Kharaziha P, Chioureas D, Baltatzis G, Fonseca P, Rodriguez P, Gogvadze V, Lennartsson L, Björklund AC, Zhivotovsky B, Grandér D, et al: Sorafenib-induced defective autophagy promotes cell death by necroptosis. Oncotarget. 6:37066–37082. 2015. View Article : Google Scholar : PubMed/NCBI
13	Goodall ML, Cramer SD and Thorburn A: Autophagy RIPs into cell death. Cell Cycle. 15:3014–3015. 2016. View Article : Google Scholar : PubMed/NCBI
14	Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT and Moscat J: The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 18:3044–3053. 1999. View Article : Google Scholar : PubMed/NCBI
15	Yan XY, Zhong XR, Yu SH, Zhang LC, Liu YN, Zhang Y, Sun LK and Su J: p62 aggregates mediated Caspase 8 activation is responsible for progression of ovarian cancer. J Cell Mol Med. 23:4030–4042. 2019. View Article : Google Scholar : PubMed/NCBI
16	Kaiser WJ, Daley-Bauer LP, Thapa RJ, Mandal P, Berger SB, Huang C, Sundararajan A, Guo H, Roback L, Speck SH, et al: RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc Natl Acad Sci USA. 111:7753–7758. 2014. View Article : Google Scholar : PubMed/NCBI
17	Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, et al: Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on cell death 2018. Cell Death Differ. 25:486–541. 2018. View Article : Google Scholar : PubMed/NCBI
18	Yu H, Su J, Xu Y, Kang J, Li H, Zhang L, Yi H, Xiang X, Liu F and Sun L: p62/SQSTM1 involved in cisplatin resistance in human ovarian cancer cells by clearing ubiquitinated proteins. Eur J Cancer. 47:1585–1594. 2011. View Article : Google Scholar : PubMed/NCBI
19	Goodall ML, Fitzwalter BE, Zahedi S, Wu M, Rodriguez D, Mulcahy-Levy JM, Green DR, Morgan M, Cramer SD and Thorburn A: The Autophagy Machinery controls cell death switching between apoptosis and necroptosis. Dev Cell. 37:337–349. 2016. View Article : Google Scholar : PubMed/NCBI
20	Chen D, Yu J and Zhang L: Necroptosis: An alternative cell death program defending against cancer. Biochim Biophys Acta. 1865:228–236. 2016.PubMed/NCBI
21	Basit F, Cristofanon S and Fulda S: Obatoclax (GX15-070) triggers necroptosis by promoting the assembly of the necrosome on autophagosomal membranes. Cell Death Differ. 20:1161–1173. 2013. View Article : Google Scholar : PubMed/NCBI
22	Dolapçi İB, Noyan S, Polat AY, Gürdal H and Dedeoğlu BG: miR-216b-5p promotes late apoptosis/necroptosis in trastuzumab-resistant SK-BR-3 cells. Turk J Biol. 47:199–207. 2023. View Article : Google Scholar : PubMed/NCBI
23	Bagherpoor AJ, Shameem M, Luo X, Seelig D and Kassie F: Inhibition of lung adenocarcinoma by combinations of sulfasalazine (SAS) and disulfiram-copper (DSF-Cu) in cell line models and mice. Carcinogenesis. 44:291–303. 2023. View Article : Google Scholar : PubMed/NCBI
24	Su J, Liu F, Xia M, Xu Y, Li X, Kang J, Li Y and Sun L: p62 participates in the inhibition of NF-κB signaling and apoptosis induced by sulfasalazine in human glioma U251 cells. Oncol Rep. 34:235–243. 2015. View Article : Google Scholar : PubMed/NCBI
25	Bray K, Mathew R, Lau A, Kamphorst JJ, Fan J, Chen J, Chen HY, Ghavami A, Stein M, DiPaola RS, et al: Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition. PLoS One. 7:e418312012. View Article : Google Scholar : PubMed/NCBI
26	Li H, Kobayashi M, Blonska M, You Y and Lin X: Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J Biol Chem. 281:13636–13643. 2006. View Article : Google Scholar : PubMed/NCBI
27	Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, Zachariou A, Lopez J, MacFarlane M, Cain K and Meier P: The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell. 43:432–448. 2011. View Article : Google Scholar : PubMed/NCBI
28	Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B and Tschopp J: Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 1:489–495. 2000. View Article : Google Scholar : PubMed/NCBI
29	Yu S, Yan X, Tian R, Xu L, Zhao Y, Sun L and Su J: An experimentally induced mutation in the UBA Domain of p62 changes the sensitivity of cisplatin by Up-Regulating HK2 localisation on the mitochondria and increasing mitophagy in A2780 ovarian cancer cells. Int J Mol Sci. 22:39832021. View Article : Google Scholar : PubMed/NCBI
30	Wang YY, Zhang J, Liu XM, Li Y, Sui J, Dong MQ, Ye K and Du LL: Molecular and structural mechanisms of ZZ domain-mediated cargo selection by Nbr1. EMBO J. 40:e1074972021. View Article : Google Scholar : PubMed/NCBI
31	Yan XY, Zhang Y, Zhang JJ, Zhang LC, Liu YN, Wu Y, Xue YN, Lu SY, Su J and Sun LK: p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1-NF-κB pathway in human ovarian cancer cells. Cancer Sci. 108:1405–1413. 2017. View Article : Google Scholar : PubMed/NCBI