Middle East Journal of Cancer

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Forms

Journal Metrics

Patuletin Caused Growth Inhibition of NCI-H460 Cancer Cells via Induction of Apoptosis

Articles in Press

Document Type : Original Article(s)

Authors

1 Department of Pharmacology, Dow University of Health Sciences, Karachi, Pakistan

2 Department of Pharmacology, Makran Medical College, Turbat, Pakistan

3 Department of Pharmacology, Liaquat National Medical College, Karachi, Pakistan

4 Department of Basic Medical Sciences, Salim Habib University, Karachi, Pakistan

5 International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

6 Hamdard Al-Majeed College of Eastern Medicine, Hamdard University, Karachi, Pakistan

10.30476/mejc.2026.107774.2301

Abstract

Background: Non-small cell lung cancer is among the major causes of mortality, globally. Previous studies demonstrated therapeutic potential of Tagetes patula flower methanolic extract against this cancer. The present study aimed at evaluating the anti-cancer potential of patuletin, a flavonoid believed to underlie medicinal effects of Tagetes flower. 
Method: This experimental study was performed on NCI-H460 cell lines. The cell viability was assessed using Sulforhodamine B assay followed by flow-cytometry-based cell cycle analysis (propidium iodide), assessment of apoptosis [mitochondrial membrane potential and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) fluorescence], and deoxyribonucleic acid [DNA (plasmid and genomic)] fragmentation. The expression of BAK, BCL-XL and p53 genes were assessed using quantitative polymerase chain reaction. The doxorubicin served as standard drug. Statistical analysis (One-way ANOVA followed by Least Significant Difference) was performed using SPSS software (v19.0, Chicago, IL, USA).  The level of significance was set at *(P < 0.05), **(P < 0.01), and ***(P < 0.005).
Results:  Patuletin arrested the growth of NCI-H460 cells with a 50% growth inhibition (GI50) of 61 µg/mL. The cell cycle analysis revealed a significant increase in Go/G1 and S phases, while G2/M phase demonstrated a decline. The apoptotic index exhibited significant elevation, while DNA remained intact. The expression of all tested genes was altered, but BAK exhibited remarkable upregulation.
Conclusion: Patuletin caused growth inhibition of NCI-H460 via the induction of BAK-mediated apoptosis. Therefore, it presents itself as a promising candidate for anti-non-small cell lung cancer drug discovery program.

Keywords

Main Subjects

Please cite this article as: Irshad S, Khan H, Khawer A, Khan MAU, Razzak A, Azhar M, et al.  Patuletin Caused Growth Inhibition of NCI-H460 Cancer Cells via Induction of Apoptosis. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.107774.2301.

References
  1. Mattiuzzi C, Lippi G. Current cancer epidemiology. J Epidemiol Glob Health. 2019;9(4):217-22. doi: 10.2991/jegh.k.191008.001. PMID: 31854162; PMCID: PMC7310786.
  2. Thandra KC, Barsouk A, Saginala K, Aluru JS, Barsouk A. Epidemiology of lung cancer. Contemp Oncol (Pozn). 2021;25(1):45-52. doi: 10.5114/wo.2021.103829. PMID: 33911981; PMCID: PMC8063897.
  3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492. Erratum in: CA Cancer J Clin. 2020;70(4):313. doi: 10.3322/caac.21609. PMID: 30207593.
  4. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, et al. The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243-60. doi: 10.1097/JTO.0000000000000630. PMID: 26291008.
  5. Sheikh HS, Munawar K, Sheikh F, Qamar MFU. Lung cancer in Pakistan. J Thorac Oncol. 2022;17(5):602-7. doi:10.1016/j.jtho.2022.01.009. PMID: 35465966.
  6. Alexander M, Kim SY, Cheng H. Update 2020: management of non-small cell lung cancer. Lung. 2020;198(6):897-907. doi: 10.1007/s00408-020-00407-5. PMID: 33175991; PMCID: PMC7656891.
  7. Lin A, Wei T, Meng H, Luo P, Zhang J. Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations. Mol Cancer. 2019;18(1):139. doi: 10.1186/s12943-019-1062-7. PMID: 31526368; PMCID: PMC6745418.
  8. Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009;109(7):3012-43. doi: 10.1021/cr900019j. PMID: 19422222; PMCID: PMC2752977.
  9. Chattopadhyay S, Sarkar SS, Saproo S, Yadav S, Antil D, Das B, et al. Apoptosis-targeted gene therapy for non-small cell lung cancer using chitosan-poly-lactic-co-glycolic acid-based nano-delivery system and CASP8 and miRs 29A-B1 and 34A. Front Bioeng Biotechnol. 2023;11:1188652. doi: 10.3389/fbioe.2023.1188652. PMID: 37484755; PMCID: PMC10360353.
  10. Neely V, Manchikalapudi A, Nguyen K, Dalton K, Hu B, Koblinski JE, et al. Targeting oncogenic mutant p53 and BCL-2 for small cell lung cancer treatment. Int J Mol Sci. 2023;24(16):13082. doi: 10.3390/ijms241613082. PMID: 37629205; PMCID: PMC10455832.
  11. Park D, Anisuzzaman ASM, Magis AT, Chen G, Xie M, Zhang G, et al. Discovery of small molecule Bak activator for lung cancer therapy. Theranostics. 2021;11(17):8500-16. doi: 10.7150/thno.59223. PMID: 34413615; PMCID: PMC8370720.
  12. Chitrakar B, Zhang M, Bhandari B. Edible flowers with the common name “marigold”: Their therapeutic values and processing. Trends Food Sci Technol. 2019;89:76-87. doi: 10.1016/j.tifs.2019.05.008.
  13. Faizi S, Siddiqi H, Bano S, Naz A, Lubna Mazhar K, Nasim S, et al. Antibacterial and antifungal activities of different parts of Tagetes patula: preparation of patuletin derivatives. Pharm Biol. 2008;46(5):309-20. doi: 10.1080/13880200801982867. PMID: 18686128.
  14. Jabeen A, Mesaik MA, Simjee SU, Bano S, Faizi S. Anti-TNF-α and anti-arthritic effect of patuletin: A rare flavonoid from Tagetes patula. Int Immunopharmacol. 2016;36:232-40. doi: 10.1016/j.intimp.2016.05.003. PMID: 27208629.
  15. Azeemi K. Rang-o-Roshni se Ilaj. Karachi: Al-Kitab Publications; 1999. p.42-43.
  16. Zheng J, Lu B, Xu B. An update on the health benefits promoted by edible flowers and involved mechanisms. Food Chem. 2021;340:127940. doi: 10.1016/j.foodchem.2020.127940. PMID: 32987120.
  17. Kashif M, Bano S, Naqvi S, Faizi S, Lubna, Ahmed Mesaik M, et al. Cytotoxic and antioxidant properties of phenolic compounds from Tagetes patula flower. Pharm Biol. 2015;53(5):672-81. doi: 10.3109/13880209.2014.931441. PMID: 25124078.
  18. Zhu W, Lv C, Wang J, Gao Q, Zhu H, Wen H. Patuletin induces apoptosis of human breast cancer SK-BR-3 cell line via inhibiting fatty acid synthase gene expression and activity. Oncol Lett. 2017;14(6):7449-54. doi: 10.3892/ol.2017.7113. PMID: 29250198; PMCID: PMC5726893.
  19. Alvarado-Sansininea JJ, Sánchez-Sánchez L, López-Muñoz H, Escobar ML, Flores-Guzmán F, Tavera-Hernández R, et al. Quercetagetin and patuletin: antiproliferative, necrotic and apoptotic activity in tumor cell lines. Molecules. 2018;23(10):2579. doi: 10.3390/molecules23102579. PMID: 30301137; PMCID: PMC6225169.
  20. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990;82(13):1107-12. doi: 10.1093/jnci/82.13.1107. PMID: 2359136.
  21. Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006;1(3):1112-6. doi: 10.1038/nprot.2006.179. PMID: 17406391.
  22. Pfeffer CM, Singh AT. Apoptosis: a target for anticancer therapy. Int J Mol Sci. 2018;19(2):448. doi: 10.3390/ijms19020448. PMID: 29393886; PMCID: PMC5855679.
  23. Sivandzade F, Bhalerao A, Cucullo L. Analysis of mitochondrial membrane potential using JC-1 dye. Bio Protoc. 2019;9(1):e3128. doi: 10.21769/BioProtoc.3128. PMID: 35083633; PMCID: PMC8782320.
  24. Mizutani H, Tada-Oikawa S, Hiraku Y, Kojima M, Kawanishi S. Mechanism of apoptosis induced by doxorubicin through generation of hydrogen peroxide. Life Sci. 2005;76(13):1439-53. doi: 10.1016/j.lfs.2004.10.040. PMID: 15680305.
  25. Ponte LGS, Pavan ICB, Mancini MCS, da Silva LGS, Morelli AP, Severino MB, et al. The hallmarks of flavonoids in cancer. Molecules. 2021;26(7):2029. doi: 10.3390/molecules26072029. PMID: 33805093; PMCID: PMC8037345.
  26. yrylkova K, Kyryachenko S, Leid M, Kioussi C. Detection of apoptosis by TUNEL assay. Methods Mol Biol. 2012;887:41-7. doi: 10.1007/978-1-61779-860-3_5. PMID: 22610562.
  27. van der Zanden SY, Qiao X, Neefjes J. New insights into activities and toxicities of doxorubicin. FEBS J. 2021;288(21):6095-111. doi: 10.1111/febs.15519. PMID: 33006134; PMCID: PMC8513754.
  28. lrich E, Kauffmann-Zeh A, Hueber AO, Williamson J, Chittenden T, Ma A, et al. Gene structure, cDNA sequence, and expression of murine Bak. Genomics. 1997;44(2):195-200. doi: 10.1006/geno.1997.4847. PMID: 9325044.
  29. Li M, Wang D, He J, Chen L, Li H. Bcl-XL: A multifunctional anti-apoptotic protein. Pharmacol Res. 2020;151:104547. doi: 10.1016/j.phrs.2019.104547. PMID: 31705974.
  30. assin O, Oren M. Drugging p53 in cancer: one protein, many targets. Nat Rev Drug Discov. 2023;22(2):127-44. doi: 10.1038/s41573-022-00571-8. PMID: 36307504.
  31. Chand P, Kumar H, Jain R, Jain A, Jain V. Flavonoids as omnipotent candidates for cancer management. S Afr J Bot. 2023;158:334-46. doi: 10.1016/j.sajb.2023.04.016.
  32. Pellegata NS, Antoniono RJ, Redpath JL, Stanbridge EJ. DNA damage and p53-mediated cell cycle arrest: a reevaluation. Proc Natl Acad Sci U S A. 1996;93(26):15209-14. doi: 10.1073/pnas.93.26.15209. PMID: 8986799; PMCID: PMC26386.
Middle East Journal of Cancer

Articles in Press, Accepted Manuscript
Available Online from 01 October 2026
Files
Share
How to cite
Statistics