Skip to main content
SpringerLink
Log in

Perturbing tumor cell metabolism with a Ru(II) photo-redox catalyst to reverse the multidrug resistance of lung cancer

  • Articles
  • Published:
Science China Chemistry Aims and scope Submit manuscript

Abstract

The novel concept of enzyme photocatalysis has recently attracted much attention in developing anticancer therapy. However, the relationship between coenzyme depletion and cellular metabolomic changes has rarely been investigated. Herein, we report the rational design of a deep-red light-triggered bis-tridentate Ru(II) photocatalyst (Ru3), which induces cell metabolism disorder to combat multidrug resistance. Ru3 exhibits promising multiple triplet excited states, a long lifetime, and high photocatalytic activity toward the coenzyme. Consequently, Ru3 shows high phototherapeutic activity (photo index = 191–833) against diverse resistant (cisplatin, 5-fluorouracil, or paclitaxel) lung cancer cells by inhibiting cellular peptide, lipid, and glycerophospholipid metabolism. We believe that cell metabolism inhibition by photo-redox catalysts is an effective form of therapeutics for drug-resistant cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. CA Cancer J Clin, 2021, 71: 209–249

    Article  PubMed  Google Scholar 

  2. Rottenberg S, Disler C, Perego P. Nat Rev Cancer, 2021, 21: 37–50

    Article  CAS  PubMed  Google Scholar 

  3. Dasari S, Bernard Tchounwou P. Eur J Pharmacol, 2014, 740: 364–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Liu W, Gust R. Chem Soc Rev, 2013, 42: 755–773

    Article  CAS  PubMed  Google Scholar 

  5. Barry NPE, Sadler PJ. Chem Commun, 2013, 49: 5106–5131

    Article  CAS  Google Scholar 

  6. Muhammad N, Guo Z. Curr Opin Chem Biol, 2014, 19: 144–153

    Article  CAS  PubMed  Google Scholar 

  7. Wang XW, Zhong XY, Liu Z, Cheng L. Nano Today, 2020, 35: 100946

    Article  CAS  Google Scholar 

  8. Liu Z, Sadler PJ. Acc Chem Res, 2014, 47: 1174–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Huang H, Banerjee S, Qiu K, Zhang P, Blacque O, Malcomson T, Paterson MJ, Clarkson GJ, Staniforth M, Stavros VG, Gasser G, Chao H, Sadler PJ. Nat Chem, 2019, 11: 1041–1048

    Article  CAS  PubMed  Google Scholar 

  10. Li M, Gebremedhin KH, Ma D, Pu Z, Xiong T, Xu Y, Kim JS, Peng X. J Am Chem Soc, 2022, 144: 163–173

    Article  CAS  PubMed  Google Scholar 

  11. Soldevila-Barreda JJ, Romero-Canelón I, Habtemariam A, Sadler PJ. Nat Commun, 2015, 6: 6582

    Article  CAS  PubMed  Google Scholar 

  12. Coverdale JPC, Romero-Canelón I, Sanchez-Cano C, Clarkson GJ, Habtemariam A, Wills M, Sadler PJ. Nat Chem, 2018, 10: 347–354

    Article  CAS  PubMed  Google Scholar 

  13. Bose S, Ngo AH, Do LH. J Am Chem Soc, 2017, 139: 8792–8795

    Article  CAS  PubMed  Google Scholar 

  14. Liu Z, Romero-Canelón I, Qamar B, Hearn JM, Habtemariam A, Barry NPE, Pizarro AM, Clarkson GJ, Sadler PJ. Angew Chem Int Ed, 2014, 53: 3941–3946

    Article  CAS  Google Scholar 

  15. Xiao W, Wang RS, Handy DE, Loscalzo J. Antioxid Redox Signal, 2018, 28: 251–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rather GM, Pramono AA, Szekely Z, Bertino JR, Tedeschi PM. Pharmacol Ther, 2021, 226: 107864

    Article  CAS  PubMed  Google Scholar 

  17. Huang C, Liang C, Sadhukhan T, Banerjee S, Fan Z, Li T, Zhu Z, Zhang P, Raghavachari K, Huang H. Angew Chem Int Ed, 2021, 60: 9474–9479

    Article  CAS  Google Scholar 

  18. Fan Z, Rong Y, Sadhukhan T, Liang S, Li W, Yuan Z, Zhu Z, Guo S, Ji S, Wang J, Kushwaha R, Banerjee S, Raghavachari K, Huang H. Angew Chem Int Ed, 2022, 61: e202202098

    CAS  Google Scholar 

  19. Wang X, Wang X, Jin S, Muhammad N, Guo Z. Chem Rev, 2019, 119: 1138–1192

    Article  CAS  PubMed  Google Scholar 

  20. Zhao J, Yan KW, Xu G, Liu X, Zhao Q, Xu CJ, Gou SH. Adv Func Mater, 2021, 31: 2008325

    Article  CAS  Google Scholar 

  21. Baggaley E, Weinstein JA, Williams JAG. Coord Chem Rev, 2012, 256: 1762–1785

    Article  CAS  Google Scholar 

  22. Zhao Q, Huang C, Li F. Chem Soc Rev, 2011, 40: 2508–2524

    Article  CAS  PubMed  Google Scholar 

  23. Conti L, Macedi E, Giorgi C, Valtancoli B, Fusi V. Coord Chem Rev, 2022, 469: 214656

    Article  CAS  Google Scholar 

  24. Jakubikova E, Chen W, Dattelbaum DM, Rein FN, Rocha RC, Martin RL, Batista ER. Inorg Chem, 2009, 48: 10720–10725

    Article  CAS  PubMed  Google Scholar 

  25. Toupin N, Steinke SJ, Nadella S, Li A, Rohrabaugh Jr. TN, Samuels ER, Turro C, Sevrioukova IF, Kodanko JJ. J Am Chem Soc, 2021, 143: 9191–9205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lameijer LN, Ernst D, Hopkins SL, Meijer MS, Askes SHC, Le Dévédec SE, Bonnet S. Angew Chem Int Ed, 2017, 56: 11549–11553

    Article  CAS  Google Scholar 

  27. Pal AK, Hanan GS. Chem Soc Rev, 2014, 43: 6184–6197

    Article  CAS  PubMed  Google Scholar 

  28. Karges J, Blacque O, Jakubaszek M, Goud B, Goldner P, Gasser G. J InOrg Biochem, 2019, 198: 110752

    Article  CAS  PubMed  Google Scholar 

  29. Ryan RT, Stevens KC, Calabro R, Parkin S, Mahmoud J, Kim DY, Heidary DK, Glazer EC, Selegue JP. Inorg Chem, 2020, 59: 8882–8892

    Article  CAS  PubMed  Google Scholar 

  30. Paul S, Kundu P, Kondaiah P, Chakravarty AR. Inorg Chem, 2021, 60: 16178–16193

    Article  CAS  PubMed  Google Scholar 

  31. Koizumi T, Tanaka K. Inorg Chim Acta, 2005, 358: 1999–2004

    Article  CAS  Google Scholar 

  32. Lifshits LM, RoqueIII JA, Konda P, Monro S, Cole HD, von Dohlen D, Kim S, Deep G, Thummel RP, Cameron CG, Gujar S, McFarland SA. Chem Sci, 2020, 11: 11740–11762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Siritanaratkul B, Megarity CF, Roberts TG, Samuels TOM, Winkler M, Warner JH, Happe T, Armstrong FA. Chem Sci, 2017, 8: 4579–4586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ji S, Wu W, Wu W, Guo H, Zhao J. Angew Chem Int Ed, 2011, 50: 1626–1629

    Article  CAS  Google Scholar 

  35. Lu Y, Wang J, McGoldrick N, Cui X, Zhao J, Caverly C, Twamley B, Ó Máille GM, Irwin B, Conway-Kenny R, Draper SM. Angew Chem Int Ed, 2016, 55: 14688–14692

    Article  CAS  Google Scholar 

  36. Yu L, Xu Y, Pu Z, Kang H, Li M, Sessler JL, Kim JS. J Am Chem Soc, 2022, 144: 11326–11337

    Article  CAS  PubMed  Google Scholar 

  37. Dikalov S. Free Radical Biol Med, 2011, 51: 1289–1301

    Article  CAS  Google Scholar 

  38. Robinson KM, Janes MS, Beckman JS. Nat Protoc, 2008, 3: 941–947

    Article  CAS  PubMed  Google Scholar 

  39. Perelman A, Wachtel C, Cohen M, Haupt S, Shapiro H, Tzur A. Cell Death Dis, 2012, 3: e430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhu J, Schwörer S, Berisa M, Kyung YJ, Ryu KW, Yi J, Jiang X, Cross JR, Thompson CB. Science, 2021, 372: 968–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Butler M, van der Meer LT, van Leeuwen FN. Trends Endocrinol Metab, 2021, 32: 367–381

    Article  CAS  PubMed  Google Scholar 

  42. Santos CR, Schulze A. FEBS J, 2012, 279: 2610–2623

    Article  CAS  PubMed  Google Scholar 

  43. Goto K, Hozumi Y, Kondo H. Biochim Biophys Acta (BBA)-Mol Cell Biol Lipids, 2006, 1761: 535–541

    CAS  Google Scholar 

  44. Hishikawa D, Hashidate T, Shimizu T, Shindou H. J Lipid Res, 2014, 55: 799–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dolce V, Rita Cappello A, Lappano R, Maggiolini M. Curr Mol Pharmacol, 2011, 4: 167–175

    Article  CAS  PubMed  Google Scholar 

  46. Jin SW, Beis D, Mitchell T, Chen JN, Stainier DYR. Development, 2005, 132: 5199–5209

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (22277153, 22007104, 21975053), Guangdong Basic and Applied Basic Research Foundation (2021B1515020050, 2023B1515020060), the Science, Technology and Innovation Commission of Shenzhen Municipality Project (JCYJ20190807152616996), the Fundamental Research Funds for the Central Universities (22lgqb37), and the Department of Science & Technology (DST), Government of India (DST/ INSPIRE/04/2019/000492). S. Banerjee thanks the Royal Society for a Newton International Fellowships Alumni 2021 (AL211023).

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. School of Pharmaceutical Science (Shenzhen) Shen Zhen Campus of Sun Yat-sen University, Shenzhen, 518107, China

    Siqi Wei, Anyi Dao, Yuzhen Xie & Huaiyi Huang

  2. Light Industry and Chemical Engineering College, Guangdong University of Technology, Guangzhou, 510006, China

    Hui Liang & Shaomin Ji

  3. College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, 518060, China

    Fengshu Cao, Qingyan Ren & Pingyu Zhang

  4. Department of Chemistry, Indian Institute of Technology (BHU), Varanasi, UP, 221005, India

    Ashish Kumar Yadav, Rajesh Kushwaha, Arif Ali Mandal & Samya Banerjee

Authors
  1. Siqi Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anyi Dao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuzhen Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fengshu Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qingyan Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ashish Kumar Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rajesh Kushwaha
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Arif Ali Mandal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Samya Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Pingyu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shaomin Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Huaiyi Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shaomin Ji or Huaiyi Huang.

Additional information

Conflict of interest

The authors declare no conflict of interest.

Supporting information

The supporting information is available online at chem.scichina.com and link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, S., Liang, H., Dao, A. et al. Perturbing tumor cell metabolism with a Ru(II) photo-redox catalyst to reverse the multidrug resistance of lung cancer. Sci. China Chem. 66, 1482–1488 (2023). https://doi.org/10.1007/s11426-022-1496-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-022-1496-0

Search

Navigation