Skip to content
2000
Volume 25, Issue 20
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Background

In various kinds of cancer, including Non-Small Cell Lung Cancer (NSCLC), treatment resistance diminishes the effectiveness of current therapeutic approaches and underscores the need for new treatment strategies.

Aims

This study aimed to investigate the combined and individual effects of the anticancer drug carboplatin and the natural antioxidant curcumin, as well as the apoptotic effects of these drugs on the A549 cancer cells.

Objectives

The synergistic effect of the combined treatment with curcumin and carboplatin on lung cancer cells was evaluated, focusing on early apoptosis, caspase-3/9 activity, and mitochondrial membrane potential.

Methods

The cytotoxic effects were determined using the MTT method. Apoptotic changes were examined using the Annexin V-FITC labeling method. Activation of caspases-9 and -3 and mitochondrial membrane potential were measured using flow cytometry.

Results

The IC values of curcumin and carboplatin against A549 cells were determined to be 60±8 μM and 100±9 μM, respectively. The combination of curcumin and carboplatin showed a synergistic effect. After treating A549 cells with carboplatin, curcumin, or the combined use of curcumin+carboplatin for 12 hours, the rates of early apoptotic cells were determined to be 9.5±1.3%, 8.1±0.3%, and 22.2±2.9%, respectively. The rate of early apoptosis in combined use was significantly higher compared to individual use. Similarly, when the combined treatment of curcumin and carboplatin was compared to the administration of carboplatin alone, a higher level of mitochondrial membrane depolarization was observed. There was a slight increase in caspase 9 activity in the combined treatment group compared to the individual treatments. Furthermore, after treating A549 cells with the specified doses, the caspase 3 activity was determined for carboplatin (0.5±0.1%), curcumin (1.9±0.0%), and the combination of both (7.3±0.8%).

Conclusion

These results indicated that the combined use of curcumin and carboplatin enhanced apoptosis and mitochondrial depolarization, demonstrating that the combined treatment of drugs reduced the toxic dose of carboplatin. However, further research is needed to comprehensively understand the potential of this effect in studies.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/acamc/10.2174/0118715206360549241209111501
2025-05-15
2025-12-16

  • From This Site

    /content/journals/acamc/10.2174/0118715206360549241209111501
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/acamc/25/20/ACAMC-25-20-02.html?itemId=/content/journals/acamc/10.2174/0118715206360549241209111501&mimeType=html&fmt=ahah

References

  1. SheG. DuJ.C. WuW. PuT.T. ZhangY. BaiR.Y. ZhangY. PangZ.D. WangH.F. RenY.J. SadoshimaJ. DengX.L. DuX.J. Hippo pathway activation mediates chemotherapy-induced anti-cancer effect and cardiomyopathy through causing mitochondrial damage and dysfunction.Theranostics202313256057710.7150/thno.79227 36632235
     [Google Scholar]
  2. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.21763 36633525
     [Google Scholar]
  3. BrayF. FerlayJ. SoerjomataramI. SiegelR.L. TorreL.A. JemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.201868639442410.3322/caac.21492 30207593
     [Google Scholar]
  4. GodoyL.A. ChenJ. MaW. LallyJ. ToomeyK.A. RajappaP. SheridanR. MahajanS. StollenwerkN. PhanC.T. ChengD. KnebelR.J. LiT. Emerging precision neoadjuvant systemic therapy for patients with resectable non-small cell lung cancer: Current status and perspectives.Biomark. Res.2023111710.1186/s40364‑022‑00444‑7 36650586
     [Google Scholar]
  5. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  6. SiegelR.L. MillerK.D. FuchsH.E. JemalA. Cancer statistics, 2022.CA Cancer J. Clin.202272173310.3322/caac.21708 35020204
     [Google Scholar]
  7. HousmanG. BylerS. HeerbothS. LapinskaK. LongacreM. SnyderN. SarkarS. Drug resistance in cancer: An overview.Cancers (Basel)2014631769179210.3390/cancers6031769 25198391
     [Google Scholar]
  8. HolohanC. Van SchaeybroeckS. LongleyD.B. JohnstonP.G. Cancer drug resistance: An evolving paradigm.Nat. Rev. Cancer2013131071472610.1038/nrc3599 24060863
     [Google Scholar]
  9. Al-LazikaniB. BanerjiU. WorkmanP. Combinatorial drug therapy for cancer in the post-genomic era.Nat. Biotechnol.201230767969210.1038/nbt.2284 22781697
     [Google Scholar]
  10. KempJ.A. ShimM.S. HeoC.Y. KwonY.J. “Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.Adv. Drug Deliv. Rev.20169831810.1016/j.addr.2015.10.019 26546465
     [Google Scholar]
  11. BensaadK. TsurutaA. SelakM.A. VidalM.N.C. NakanoK. BartronsR. GottliebE. VousdenK.H. TIGAR, a p53-inducible regulator of glycolysis and apoptosis.Cell2006126110712010.1016/j.cell.2006.05.036 16839880
     [Google Scholar]
  12. BoulikasT. VougioukaM. Cisplatin and platinum drugs at the molecular level (Review).Oncol. Rep.20031061663168210.3892/or.10.6.1663 14534679
     [Google Scholar]
  13. ChurchD.N. BahlA. Clinical review – Small cell carcinoma of the bladder.Cancer Treat. Rev.200632858859310.1016/j.ctrv.2006.07.013 17008012
     [Google Scholar]
  14. FuS. KavanaghJ.J. HuW. BastR.C.Jr Clinical application of oxaliplatin in epithelial ovarian cancer.Int. J. Gynecol. Cancer20061651717173210.1136/ijgc‑00009577‑200609000‑00001 17009963
     [Google Scholar]
  15. ChoyH. Satraplatin: an orally available platinum analog for the treatment of cancer.Expert Rev. Anticancer Ther.20066797398210.1586/14737140.6.7.973 16831070
     [Google Scholar]
  16. PasettoL.M. D’AndreaM.R. BrandesA.A. RossiE. MonfardiniS. The development of platinum compounds and their possible combination.Crit. Rev. Oncol. Hematol.2006601597510.1016/j.critrevonc.2006.02.003 16806960
     [Google Scholar]
  17. Di LielloR. CiaramellaV. BarraG. VendittiM. Della CorteC.M. PapaccioF. SparanoF. ViscardiG. IacovinoM.L. MinucciS. FasanoM. CiardielloF. MorgilloF. Ex vivo lung cancer spheroids resemble treatment response of a patient with NSCLC to chemotherapy and immunotherapy: Case report and translational study.ESMO Open201944e00053610.1136/esmoopen‑2019‑000536 31555484
     [Google Scholar]
  18. D’AbroscaB. CiaramellaV. GrazianiV. PapaccioF. Della CorteC.M. PotenzaN. FiorentinoA. CiardielloF. MorgilloF. Urtica dioica L. inhibits proliferation and enhances cisplatin cytotoxicity in NSCLC cells via Endoplasmic Reticulum-stress mediated apoptosis.Sci. Rep.201991498610.1038/s41598‑019‑41372‑1 30899059
     [Google Scholar]
  19. Della CorteC.M. CiaramellaV. RamkumarK. VicidominiG. FiorelliA. NardoneV. CappabiancaS. CozzolinoI. Zito MarinoF. Di GuidaG. WangQ. CardnellR. GayC.M. CiardielloD. MartinelliE. TroianiT. MartiniG. NapolitanoS. WangJ. ByersL.A. CiardielloF. MorgilloF. Triple blockade of Ido-1, PD-L1 and MEK as a potential therapeutic strategy in NSCLC.J. Transl. Med.202220154110.1186/s12967‑022‑03730‑y 36419183
     [Google Scholar]
  20. WangD. LippardS.J. Cellular processing of platinum anticancer drugs.Nat. Rev. Drug Discov.20054430732010.1038/nrd1691 15789122
     [Google Scholar]
  21. RosenbergB. VancampL. TroskoJ.E. MansourV.H. Platinum compounds: A new class of potent antitumour agents.Nature19692225191385386
     [Google Scholar]
  22. AggarwalB.B. KumarA. BhartiA.C. Anticancer potential of curcumin: preclinical and clinical studies.Anticancer Res.2003231/A36398
     [Google Scholar]
  23. LestariM.L.A.D. IndrayantoG. Curcumin.Profiles Drug Subst. Excip. Relat. Methodol.20143911320410.1016/B978‑0‑12‑800173‑8.00003‑9 24794906
     [Google Scholar]
  24. MahadyG.B. PendlandS.L. YunG. LuZ.Z. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen.Anticancer Res.2002226C41794181 12553052
     [Google Scholar]
  25. ReddyR.C. VatsalaP.G. KeshamouniV.G. PadmanabanG. RangarajanP.N. Curcumin for malaria therapy.Biochem. Biophys. Res. Commun.2005326247247410.1016/j.bbrc.2004.11.051 15582601
     [Google Scholar]
  26. Vera-RamirezL. Pérez-LopezP. Varela-LopezA. Ramirez-TortosaM.C. BattinoM. QuilesJ.L. Curcumin and liver disease.Biofactors20133918810010.1002/biof.1057 23303639
     [Google Scholar]
  27. WrightL. FryeJ. GortiB. TimmermannB. FunkJ. Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer.Curr. Pharm. Des.201319346218622510.2174/1381612811319340013 23448448
     [Google Scholar]
  28. ChenQ.Y. WuL.J. WuY.Q. LuG.H. JiangZ.Y. ZhanJ.W. JieY. ZhouJ.Y. Molecular mechanism of trifluoperazine induces apoptosis in human A549 lung adenocarcinoma cell lines.Mol. Med. Rep.20092581181710.3892/mmr_00000177 21475906
     [Google Scholar]
  29. TianD. ZhuH. LiangY. Effects and mechanisms of curcuminon apoptosis of lung adenocarcinoma A549 cells.Chin. J. Clin. Pharmacol.200615810
     [Google Scholar]
  30. GoelA. AggarwalB.B. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs.Nutr. Cancer201062791993010.1080/01635581.2010.509835 20924967
     [Google Scholar]
  31. ChanvorachoteP. PongrakhananonV. WannachaiyasitS. LuanpitpongS. RojanasakulY. NimmannitU. Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation.Cancer Invest.200927662463510.1080/07357900802653472 19283527
     [Google Scholar]
  32. RocksN. BekaertS. CoiaI. PaulissenG. GuédersM. EvrardB. Van HeugenJ-C. ChiapP. FoidartJ-M. NoelA. CataldoD. Curcumin–cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer.Br. J. Cancer201210771083109210.1038/bjc.2012.379 22929882
     [Google Scholar]
  33. SenS. SharmaH. SinghN. Curcumin enhances Vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway.Biochem. Biophys. Res. Commun.200533141245125210.1016/j.bbrc.2005.04.044 15883009
     [Google Scholar]
  34. YinH. GuoR. XuY. ZhengY. HouZ. DaiX. ZhangZ. ZhengD. XuH. Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer.Acta Biochim. Biophys. Sin. (Shanghai)201244214715310.1093/abbs/gmr106 22126905
     [Google Scholar]
  35. MosmannT. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.J. Immunol. Methods1983651-2556310.1016/0022‑1759(83)90303‑4 6606682
     [Google Scholar]
  36. EzerM. The effect of carboplatin and curcumin combinations on oxidative stress in lung cancer.Master’s Thesis, Anadolu University2019
     [Google Scholar]
  37. RobinsonL.A. RuckdeschelJ.C. WagnerH.Jr StevensC.W. Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition).Chest20071323)(Suppl.243S265S10.1378/chest.07‑1379 17873172
     [Google Scholar]
  38. PrasadK.N. Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity.Integr. Cancer Ther.20043431032210.1177/1534735404270936 15523102
     [Google Scholar]
  39. UngerF.T. KlasenH.A. TchartchianG. de WildeR.L. WitteI. DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells.BMC Cancer20099135910.1186/1471‑2407‑9‑359 19818145
     [Google Scholar]
  40. ChenH.H. ChenT.W. LinH. Pravastatin attenuates carboplatin-induced nephrotoxicity in rodents via peroxisome proliferator-activated receptor α-regulated heme oxygenase-1.Mol. Pharmacol.2010781364510.1124/mol.109.061101 20368269
     [Google Scholar]
  41. BarjotC. TournaireM. CastagninoC. VigorC. VercauterenJ. RossiJ.F. Evaluation of antitumor effects of two vine stalk oligomers of resveratrol on a panel of lymphoid and myeloid cell lines: Comparison with resveratrol.Life Sci.20078123-241565157410.1016/j.lfs.2007.08.047 18001803
     [Google Scholar]
  42. LimaC.F. Fernandes-FerreiraM. Pereira-WilsonC. Phenolic compounds protect HepG2 cells from oxidative damage: Relevance of glutathione levels.Life Sci.200679212056206810.1016/j.lfs.2006.06.042 16857214
     [Google Scholar]
  43. WangJ-Y. WangX. WangX-J. ZhengB-Z. WangY. WangX. LiangB. Curcumin inhibits the growth via Wnt/β-catenin pathway in non-small-cell lung cancer cells.Eur. Rev. Med. Pharmacol. Sci.2018222174927499 30468498
     [Google Scholar]
  44. ChuangS.E. KuoM.L. HsuC-H. ChenC.R. LinJ.K. LaiG.M. HsiehC.Y. ChengA.L. Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis.Carcinogenesis200021233133510.1093/carcin/21.2.331 10657978
     [Google Scholar]
  45. SrimalR.C. DhawanB.N. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent.J. Pharm. Pharmacol.201125644745210.1111/j.2042‑7158.1973.tb09131.x 4146582
     [Google Scholar]
  46. ChouT.C. Drug combination studies and their synergy quantification using the Chou-Talalay method.Cancer Res.201070244044610.1158/0008‑5472.CAN‑09‑1947 20068163
     [Google Scholar]
  47. ChouT.C. TalalayP. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors.Adv. Enzyme Regul.198422275510.1016/0065‑2571(84)90007‑4 6382953
     [Google Scholar]
  48. KangJ.H. KangH.S. KimI.K. LeeH.Y. HaJ.H. YeoC.D. KangH.H. MoonH.S. LeeS.H. Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin.Exp. Biol. Med. (Maywood)2015240111416142510.1177/1535370215571881 25716014
     [Google Scholar]
  49. HassanM. WatariH. AbuAlmaatyA. OhbaY. SakuragiN. Apoptosis and molecular targeting therapy in cancer.Biomed Res. Int.2014201415084510.1155/2014/150845
     [Google Scholar]
  50. XuX.Y. MengX. LiS. GanR.Y. LiY. LiH.B. Bioactivity, health benefits, and related molecular mechanisms of curcumin: Current progress, challenges, and perspectives.Nutrients20181010155310.3390/nu10101553 30347782
     [Google Scholar]
  51. MaL. LiW. WangR. NanY. WangQ. LiuW. JinF. Resveratrol enhanced anticancer effects of cisplatin on non-small cell lung cancer cell lines by inducing mitochondrial dysfunction and cell apoptosis.Int. J. Oncol.20154741460146810.3892/ijo.2015.3124 26314326
     [Google Scholar]
  52. CaoM.R. LiQ. LiuZ.L. LiuH.H. WangW. LiaoX.L. PanY.L. JiangJ.W. Harmine induces apoptosis in HepG2 cells via mitochondrial signaling pathway.Hepatobiliary Pancreat. Dis. Int.201110659960410.1016/S1499‑3872(11)60102‑1 22146623
     [Google Scholar]
  53. Flow cytometry in analysis of cell cycle and apoptosis. DarzynkiewiczZ. BednerE. SmolewskiP. Seminars in hematology.2001
     [Google Scholar]
  54. ÖzdemiR. F.; Sever, A.; Keçeci, Y.Ö.; Incesu, Z. Resveratrol increases the sensitivity of breast cancer MDA-MB-231 cell line to cisplatin by regulating intrinsic apoptosis.Iran. J. Basic Med. Sci.20212416672 33643572
     [Google Scholar]
/content/journals/acamc/10.2174/0118715206360549241209111501
Loading
Combined Effects of Curcumin and Carboplatin on Mitochondrial Depolarization and Caspase Activation in Human Lung Adenocarcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry 25, 1588 (2025); https://doi.org/10.2174/0118715206360549241209111501
/content/journals/acamc/10.2174/0118715206360549241209111501
/content/journals/acamc/10.2174/0118715206360549241209111501
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): annexin V-FITC labeling method; carboplatin; caspase 9 activity; caspase activation; Curcumin; mitochondrial apoptosis

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test