Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
December-2022 Volume 61 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2022 Volume 61 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.pdf
Article Open Access

Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis

  • Authors:
    • Xiaofeng Liu
    • Yang Hai
    • Jinqu Dong
    • Lan Xu
    • Wenqian Hou
    • Jing Su
    • Weiyu Ren
    • Dongling Liu
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China, Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 157
    |
    Published online on: November 1, 2022
       https://doi.org/10.3892/ijo.2022.5447
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

KRAS is a biomarker for non‑small cell lung cancer‑targeted therapy, but there is currently no effective KRAS‑targeting medication. Realgar is an impelling anticancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC50 of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non‑KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 µg/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe2+, reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer‑1. Realgar decreased phosphorylated p‑Raf, p‑ERK1/2 and increased p‑p38 and p‑JNK, whereas only p‑Raf was abolished by Fer‑1. Raf inhibitor Sorafenib accelerated the realgar‑induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti‑KRAS mutant lung cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Huang J, Deng Y, Tin MS, Lok V, Ngai CH, Zhang L, Lucero-Prisno DE III, Xu W, Zheng ZJ, Elcarte E, et al: Distribution, risk factors, and temporal trends for lung cancer incidence and mortality: A global analysis. Chest. 161:1101–1111. 2022. View Article : Google Scholar : PubMed/NCBI

2 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

3 

Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Ryan MB and Corcoran RB: Therapeutic strategies to target RAS-mutant cancers. Nat Rev Clin Oncol. 15:709–720. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Nagasaka M, Li Y, Sukari A, Ou SI, Al-Hallak MN and Azmi AS: KRAS G12C game of thrones, which direct KRAS inhibitor will claim the iron throne? Cancer Treat Rev. 84:1019742020. View Article : Google Scholar : PubMed/NCBI

6 

Rodak O, Peris-Díaz MD, Olbromski M, Podhorska-Okołów M and Dzięgiel P: Current landscape of non-small cell lung cancer: Epidemiology, histological classification, targeted therapies, and immunotherapy. Cancers (Basel). 13:47052021. View Article : Google Scholar

7 

Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, et al: Sotorasib for lung cancers with KRAS G12C-mutation. N Engl J Med. 384:2371–2381. 2021. View Article : Google Scholar : PubMed/NCBI

8 

Ryan MB, Coker O, Sorokin A, Fella K, Barnes H, Wong E, Kanikarla P, Gao F, Zhang Y, Zhou L, et al: KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy. Cell Rep. 39:1109932022. View Article : Google Scholar

9 

Xiaoxia X, Jing S, Dongbin X, Yonggang T, Jingke Z, Yanying Z and Hulai W: Realgar nanoparticles inhibit migration, invasion and metastasis in a mouse model of breast cancer by suppressing matrix metalloproteinases and angiogenesis. Curr Drug Deliv. 17:148–158. 2020. View Article : Google Scholar : PubMed/NCBI

10 

Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX, et al: Dissection of mechanisms of Chinese medicinal formula realgar-indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA. 105:4826–4831. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Lu DP, Qiu JY, Jiang B, Wang Q, Liu KY, Liu YR and Chen SS: Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia: A pilot report. Blood. 99:3136–3143. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Huang SL, Guo AX, Xiang Y, Wand XB, Lin HX and Fu L: Clinical study on the treatment of acute promyelocytic leukemia with composite indigo naturalis tablets. Chin J Hematol. 16:26–28. 1995.

13 

Shi G and Shan G: Effects of yellow loquat on changes in immune function, hemorheology and coagulation function in patients with lung cancer. China Tradit Chin Med Sci Technol. 20:115–116. 2013.

14 

Yang FR, Zhao YF, Hu XW, Liu ZK, Yu XD, Li CY, Li XR and Li HJ: Nano-realgar suppresses lung cancer stem cell growth by repressing metabolic reprogramming. Gene. 788:1456662021. View Article : Google Scholar : PubMed/NCBI

15 

Liu D, Zhi D, Zhou T, Yu Q, Wan F, Bai Y and Li H: Realgar bioleaching solution is a less toxic arsenic agent in suppressing the Ras/MAPK pathway in Caenorhabditis elegans. Environ Toxicol Pharmacol. 35:292–299. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Drosten M and Barbacid M: Targeting the MAPK Pathway in KRAS-driven tumors. Cancer Cell. 37:543–550. 2020. View Article : Google Scholar : PubMed/NCBI

17 

Moore AR, Rosenberg SC, McCormick F and Malek S: RAS-targeted therapies: Is the undruggable drugged? Nat Rev Drug Discov. 19:533–552. 2020. View Article : Google Scholar : PubMed/NCBI

18 

Karoulia Z, Gavathiotis E and Poulikakos PI: New perspectives for targeting RAF kinase in human cancer. Nat Rev Cancer. 17:676–691. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Karnoub AE and Weinberg RA: Ras oncogenes: Split personalities. Nat Rev Mol Cell Biol. 9:517–531. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Leevers SJ, Paterson HF and Marshall CJ: Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature. 369:411–414. 1994. View Article : Google Scholar : PubMed/NCBI

21 

Stokoe D, Macdonald SG, Cadwallader K, Symons M and Hancock JF: Activation of Raf as a result of recruitment to the plasma membrane. Science. 264:1463–1467. 1994. View Article : Google Scholar : PubMed/NCBI

22 

Peng SB, Henry JR, Kaufman MD, Lu WP, Smith BD, Vogeti S, Rutkoski TJ, Wise S, Chun L, Zhang Y, et al: Inhibition of RAF isoforms and active dimers by LY3009120 leads to anti-tumor activities in RAS or BRAF mutant cancers. Cancer Cell. 28:384–398. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Awad MM, Liu S, Rybkin II, Arbour KC, Dilly J, Zhu VW, Johnson ML, Heist RS, Patil T, Riely GJ, et al: Acquired resistance to KRASG12C inhibition in cancer. N Engl J Med. 384:2382–2393. 2021. View Article : Google Scholar : PubMed/NCBI

24 

Tanaka N, Lin JJ, Li C, Ryan MB, Zhang J, Kiedrowski LA, Michel AG, Syed MU, Fella KA, Sakhi M, et al: Clinical acquired resistance to KRASG12C inhibition through a novel KRAS switch-II pocket mutation and polyclonal alterations converging on RAS-MAPK reactivation. Cancer Discov. 11:1913–1922. 2021. View Article : Google Scholar : PubMed/NCBI

25 

Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, et al: RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 447:864–868. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Chen X, Kang R, Kroemer G and Tang D: Broadening horizons: The role of ferroptosis in cancer. Nat Rev Clin Oncol. 18:280–296. 2021. View Article : Google Scholar : PubMed/NCBI

27 

Chen P, Li X, Zhang R, Liu S, Xiang Y, Zhang M, Chen X, Pan T, Yan L, Feng J, et al: Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation. Theranostics. 10:5107–5119. 2020. View Article : Google Scholar :

28 

Balihodzic A, Prinz F, Dengler MA, Calin GA, Jost PJ and Pichler M: Non-coding RNAs and ferroptosis: Potential implications for cancer therapy. Cell Death Differ. 29:1094–1106. 2022. View Article : Google Scholar : PubMed/NCBI

29 

Alemán MR, Santolaria F, Batista N, de La Vega M, González-Reimers E, Milena A, Llanos M and Gómez-Sirvent JL: Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition? Cytokine. 19:21–26. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Liang C, Zhang X, Yang M and Dong X: Recent progress in ferroptosis inducers for cancer therapy. Adv Mater. 31:19041972019. View Article : Google Scholar

31 

Gammella E, Buratti P, Cairo G and Recalcati S: The transferrin receptor: The cellular iron gate. Metallomics. 9:1367–1375. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Yang WS and Stockwell BR: Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 15:234–245. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Chen X, Yu C, Kang R, Kroemer G and Tang D: Cellular degradation systems in ferroptosis. Cell Death Differ. 28:1135–1148. 2021. View Article : Google Scholar : PubMed/NCBI

34 

Deng S, Wu D, Li L, Liu T, Zhang T, Li J, Yu Y, He M, Zhao YY, Han R and Xu Y: miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in lung adenocarcinoma cell line A549. Biochem Biophys Res Commun. 549:54–60. 2021. View Article : Google Scholar : PubMed/NCBI

35 

Kukulj S, Jaganjac M, Boranic M, Krizanac S, Santic Z and Poljak-Blazi M: Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer. Med Oncol. 27:268–277. 2010. View Article : Google Scholar

36 

Jaune-Pons E and Vasseur S: Role of amino acids in regulation of ROS balance in cancer. Arch Biochem Biophys. 689:1084382020. View Article : Google Scholar : PubMed/NCBI

37 

Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T, Bork P, et al: The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49(D1): D605–D612. 2021. View Article : Google Scholar

38 

Nie Q, Hu Y, Yu X, Li X and Fang X: Induction and application of ferroptosis in cancer therapy. Cancer Cell Int. 22:122022. View Article : Google Scholar : PubMed/NCBI

39 

Xu T, Ding W, Ji X, Ao X, Liu Y, Yu W and Wang J: Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med. 23:4900–4912. 2019. View Article : Google Scholar : PubMed/NCBI

40 

Sun L, Dong H, Zhang W, Wang N, Ni N, Bai X and Liu N: Lipid peroxidation, GSH depletion, and SLC7A11 inhibition are common causes of EMT and ferroptosis in A549 cells, but different in specific mechanisms. DNA Cell Biol. 40:172–183. 2021. View Article : Google Scholar

41 

Wang H, Liu C, Zhao Y and Gao G: Mitochondria regulation in ferroptosis. Eur J Cell Biol. 99:1510582020. View Article : Google Scholar

42 

Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB and Jiang X: Role of mitochondria in ferroptosis. Mol Cell. 73:354–363.e3. 2019. View Article : Google Scholar :

43 

Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, et al: Regulation of ferroptotic cancer cell death by GPX4. Cell. 156:317–331. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI

45 

Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, et al: ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 13:91–98. 2017. View Article : Google Scholar :

46 

Su LJ, Zhang JH, Gomez H, Murugan R, Hong X, Xu D, Jiang F and Peng ZY: Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019:50808432019. View Article : Google Scholar : PubMed/NCBI

47 

Chang WT, Bow YD, Fu PJ, Li CY, Wu CY, Chang YH, Teng YN, Li RN, Lu MC, Liu YC and Chiu CC: A marine terpenoid, heteronemin, induces both the apoptosis and ferroptosis of hepatocellular carcinoma cells and involves the ROS and MAPK pathways. Oxid Med Cell Longev. 2021:76890452021. View Article : Google Scholar : PubMed/NCBI

48 

Zhao J and Luo Z: Discovery of Raf family is a milestone in deciphering the Ras-mediated intracellular signaling pathway. Int J Mol Sci. 23:51582022. View Article : Google Scholar : PubMed/NCBI

49 

Liu G, Song Y, Li C, Liu R, Chen Y, Yu L, Huang Q, Zhu D, Lu C, Yu X, et al: Arsenic compounds: The wide application and mechanisms applied in acute promyelocytic leukemia and carcinogenic toxicology. Eur J Med Chem. 221:1135192021. View Article : Google Scholar : PubMed/NCBI

50 

Lin CC, Huang YK, Cho CF, Lin YS, Lo CC, Kuo TT, Tseng GC, Cheng WC, Chang WC, Hsiao TH, et al: Targeting positive feedback between BASP1 and EGFR as a therapeutic strategy for lung cancer progression. Theranostics. 10:10925–10939. 2020. View Article : Google Scholar : PubMed/NCBI

51 

Cuenda A and Rousseau S: p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta. 1773:1358–1375. 2007. View Article : Google Scholar : PubMed/NCBI

52 

Huang CH, Lee YC, Chiou JT, Shi YJ, Wang LJ and Chang LS: Arsenic trioxide-induced p38 MAPK and Akt mediated MCL1 downregulation causes apoptosis of BCR-ABL1-positive leukemia cells. Toxicol Appl Pharmacol. 397:1150132020.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

53 

Wu MF, Huang YH, Chiu LY, Cherng SH, Sheu GT and Yang TY: Curcumin induces apoptosis of chemoresistant lung cancer cells via ROS-regulated p38 MAPK phosphorylation = Arsenic trioxide-induced p38 MAPK and Akt mediated MCL1 downregulation causes apoptosis of BCR-ABL1-positive leukemia cells. Int J Mol Sci. 23:82482022. View Article : Google Scholar : PubMed/NCBI

54 

Xiao X, Guo L, Dai W, Yan B, Zhang J, Yuan Q, Zhou L, Shan L and Efferth Y: Green tea-derived theabrownin suppresses human non-small cell lung carcinoma in xenograft model through activation of not only p53 signaling but also MAPK/JNK signaling pathway. J Ethnopharmacol. 291:1151672022. View Article : Google Scholar : PubMed/NCBI

55 

Liu Z, Zhao M, Jiang X, Zhang Y, Zhang S, Xu Y, Ren H, Su H, Wang H and Qiu X: Upregulation of KLHL17 promotes the proliferation and migration of non-small cell lung cancer by activating the Ras/MAPK signaling pathway. Lab Invest. Aug 17–2022.Epub ahead of print. View Article : Google Scholar

56 

Han YH, Moon HJ, You BR, Kim SZ, Kim SH and Park WH: The effect of MAPK inhibitors on arsenic trioxide-treated Calu-6 lung cells in relation to cell death, ROS and GSH levels. Anticancer Res. 29:3837–3844. 2009.PubMed/NCBI

57 

Yang X, Wu X, Wu X, Huang L, Song J, Yung C, He Z and Li Y: The flavagline compound 1-(2-(dimethylamino) acetyl)-rocaglaol induces apoptosis in K562 cells by regulating the PI3K/Akt/mTOR, JAK2/STAT3, and MAPK pathways. Drug Des Devel Ther. 16:2545–2557. 2022. View Article : Google Scholar :

58 

Lee H, Lee HJ, Bae IJ, Kim JJ and Kim SH: Inhibition of STAT3/VEGF/CDK2 axis signaling is critically involved in the antiangiogenic and apoptotic effects of arsenic herbal mixture PROS in non-small lung cancer cells. Oncotarget. 8:101771–101783. 2017. View Article : Google Scholar : PubMed/NCBI

59 

Liu Z, Zhao Q, Zuo ZX, Yuan SQ, Yu K, Zhang Q, Zhang X, Sheng H, Ju HQ, Cheng H, et al: Systematic analysis of the aberrances and functional implications of ferroptosis in cancer. iScience. 23:1013022020. View Article : Google Scholar : PubMed/NCBI

60 

Yong WP, Rha SY, Tan IB, Choo SP, Syn NL, Koh V, Tan SH, Asuncion BR, Sundar R, So JB, et al: Real-time tumor gene expression profiling to direct gastric cancer chemotherapy: Proof-of-concept '3G' trial. Clin Cancer Res. 24:5272–5281. 2018. View Article : Google Scholar : PubMed/NCBI

61 

Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R and Gu W: Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 520:57–62. 2015. View Article : Google Scholar : PubMed/NCBI

62 

Lim JKM and Leprivier G: The impact of oncogenic RAS on redox balance and implications for cancer development. Cell Death Dis. 10:9552019. View Article : Google Scholar : PubMed/NCBI

63 

Lim JKM, Delaidelli A, Minaker SW, Zhang HF, Colovic M, Yang H, Negri GL, von Karstedt S, Lockwood WW, Schaffer P, et al: Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance. Proc Natl Acad Sci USA. 116:9433–9442. 2019. View Article : Google Scholar : PubMed/NCBI

64 

Baek S, Choi CM, Ahn SH, Lee JW, Gong G, Ryu JS, Oh SJ, Bacher-Stier C, Fels L, Koglin N, et al: Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC-transporter using positron emission tomography in patients with non-small cell lung or breast cancer. Clin Cancer Res. 18:5427–5437. 2012. View Article : Google Scholar : PubMed/NCBI

65 

Hu K, Li K, Lv J, Feng J, Chen J, Wu H, Cheng F, Jiang W, Wang J, Pei H, et al: Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma. J Clin Invest. 130:1752–1766. 2020. View Article : Google Scholar :

66 

Zhang N, Huang J, Xu M and Wang Y: LncRNA T-UCR Uc.339/miR-339/SLC7A11 axis regulates the metastasis of ferroptosis-induced lung adenocarcinoma. J Cancer. 13:1945–1957. 2022. View Article : Google Scholar : PubMed/NCBI

67 

Liu XY, Wei DG and Li RS: Capsaicin induces ferroptosis of NSCLC by regulating SLC7A11/GPX4 signaling in vitro. Sci Rep. 12:119962022. View Article : Google Scholar : PubMed/NCBI

68 

Gao H, Bai Y, Jia Y, Zhao Y, Kang R, Tang D and Dai E: Ferroptosis is a lysosomal cell death process. Biochem Biophys Res Commun. 503:1550–1556. 2018. View Article : Google Scholar : PubMed/NCBI

69 

Ma X, Yan W and He N: Lidocaine attenuates hypoxia/reoxygenation-induced inflammation, apoptosis and ferroptosis in lung epithelial cells by regulating the p38 MAPK pathway. Mol Med Rep. 25:1502022. View Article : Google Scholar :

70 

Yang J, Mo J, Dai J, Ye C, Cen W, Zheng X, Jiang L and Ye L: Cetuximab promotes RSL3-induced ferroptosis by suppressing the Nrf2/HO-1 signalling pathway in KRAS mutant colorectal cancer. Cell Death Dis. 12:10792021. View Article : Google Scholar : PubMed/NCBI

71 

Zhu K, Zhu X, Sun S, Yang W, Liu S, Tang Z, Zhang R, Li J, Shen T and Hei M: Inhibition of TLR4 prevents hippocampal hypoxic-ischemic injury by regulating ferroptosis in neonatal rats. Exp Neurol. 345:1138282021. View Article : Google Scholar : PubMed/NCBI

72 

Wang Y, Zhang L, Yao C, Ma Y and Liu Y: Epithelial membrane protein 1 promotes sensitivity to RSL3-induced ferroptosis and intensifies gefitinib resistance in head and neck cancer. Oxid Med Cell Longev. 2022:47506712022.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu X, Hai Y, Dong J, Xu L, Hou W, Su J, Ren W and Liu D: Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis. Int J Oncol 61: 157, 2022.
APA
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J. ... Liu, D. (2022). Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis. International Journal of Oncology, 61, 157. https://doi.org/10.3892/ijo.2022.5447
MLA
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J., Ren, W., Liu, D."Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis". International Journal of Oncology 61.6 (2022): 157.
Chicago
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J., Ren, W., Liu, D."Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis". International Journal of Oncology 61, no. 6 (2022): 157. https://doi.org/10.3892/ijo.2022.5447
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Hai Y, Dong J, Xu L, Hou W, Su J, Ren W and Liu D: Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis. Int J Oncol 61: 157, 2022.
APA
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J. ... Liu, D. (2022). Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis. International Journal of Oncology, 61, 157. https://doi.org/10.3892/ijo.2022.5447
MLA
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J., Ren, W., Liu, D."Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis". International Journal of Oncology 61.6 (2022): 157.
Chicago
Liu, X., Hai, Y., Dong, J., Xu, L., Hou, W., Su, J., Ren, W., Liu, D."Realgar‑induced KRAS mutation lung cancer cell death via KRAS/Raf/MAPK mediates ferroptosis". International Journal of Oncology 61, no. 6 (2022): 157. https://doi.org/10.3892/ijo.2022.5447
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team