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Year 2025, Volume: 15 Issue: 2, 169 - 174, 29.08.2025
https://doi.org/10.26650/experimed.1591042

Abstract

Project Number

1919B012004879

References

  • 1. Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol 2021; 14(1): 44. google scholar
  • 2. Braun TP, Eide CA, Druker BJ. Response and resistance to BCR-ABL1-targeted therapies. Cancer Cell 2020; 37(4): 530-42. google scholar
  • 3. Grassi S, Palumbo S, Mariotti V, Liberati D, Guerrini F, Ciabatti E, et al. The WNT pathway is relevant for the BCR-ABL1-independent resistance in chronic myeloid leukemia. Front Oncol 2019; 9: 532. google scholar
  • 4. Chiarini F, Paganelli F, Martelli AM, Evangelisti C. The role played by Wnt/β-catenin signaling pathway in acute lymphoblastic leukemia. Int J Mol Sci 2020; 21(3): 1098. google scholar
  • 5. Khan F, Negi K, Kumar T. Effect of sprouted fenugreek seeds on various diseases: A review. J. Diabetes Metab Disord Control 2018; 5: 119-125. google scholar
  • 6. Ahmad A, Alghamdi SS, Mahmood K, Afzal M. Fenugreek a multipurpose crop: potentialities and improvements. Saudi J Biol Sci 2016; 23(2): 300-10. google scholar
  • 7. Shabbeer S, Sobolewski M, Anchoori RK, Kachhap S, Hidalgo M, Jimeno A, et al. Fenugreek: a naturally occurring edible spice as an anticancer agent. Cancer Biol Ther 2009; 8(3): 272-78. google scholar
  • 8. Müschen M. WNT/β-Catenin Signaling in Leukemia. In: Goss K, Kahn M. (eds) Targeting the Wnt pathway in cancer. Springer, New York, NY. 2011. p.129–42. google scholar
  • 9. Pehlivan M, Soyoz M, Cerci B, Karahan Coven HI, Yuce Z, Sercan, H. sFRP1 expression induces miRNAs that modulate Wnt signaling in chronic myeloid leukemia cells. Mol Biol 2020; 54(4): 626-33. google scholar
  • 10. Bavaro L, Martelli M, Cavo M, Soverini S. Mechanisms of disease progression and resistance to tyrosine kinase inhibitor therapy in chronic myeloid leukemia: an update. Int J Mol Sci 2019; 20(24): 6141. google scholar
  • 11. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990; 44(4): 301-6. google scholar
  • 12. Losso JN, Holliday DL, Finley JW, Martin RJ, Rood JC, Yu Y, et al. Fenugreek bread: a treatment for diabetes mellitus. J Med Food 2009; 12(5): 1046-49. google scholar
  • 13. Pandian RS, Anuradha CV, Viswanathan P. Gastroprotective effect of fenugreek seeds (Trigonella foenum graecum) on experimental gastric ulcer in rats. J Ethnopharmacol 2002; 81(3): 393-97. google scholar
  • 14. Uemura T, Hirai S, Mizoguchi N, Goto T, Lee JY, Taketani K, et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. Mol Nutr Food Res 2010; 54(11): 1596-608. google scholar
  • 15. Chaudhary S, Chaudhary PS, Chikara SK, Sharma MC, Iriti M. Review on fenugreek (Trigonella foenum-graecum L.) and its important secondary metabolite diosgenin. Not Bot Horti Agrobot Cluj‑Napoca 2018; 46(1): 22-31. google scholar
  • 16. Alsemari A, Alkhodairy F, Aldakan A, Hohanna MA, Bahoush E, Shinwari Z, et al. The selective cytotoxic anti-cancer properties and proteomic analysis of Trigonella Foenum-Graecum. BMC Complement Med Ther 2014; 14: 114. google scholar
  • 17. Khalil MI, Ibrahim MM, El-Gaaly GA, Sultan AS. Trigonella foenum (Fenugreek) induced apoptosis in hepatocellular carcinoma cell line, HepG2, mediated by upregulation of p53 and proliferating cell nuclear antigen. BioMed Res Int 2015; 2015: 914645. google scholar
  • 18. Alshatwi AA, Shafi G, Hasan TN, Syed NA, Khoja KK. Fenugreek induced apoptosis in breast cancer MCF-7 cells mediated independently by Fas receptor change. Asian Pac J Cancer Prev 2013; 14(10): 5783-8. google scholar
  • 19. Khoja KK, Howes MJR, Hider R, Sharp PA, Farrell IW, Latunde-Dada GO. Cytotoxicity of fenugreek sprout and seed extracts and their bioactive constituents on MCF-7 breast cancer cells. Nutrients 2022; 14(4): 784. google scholar
  • 20. Sebastian KS, Thampan RV. Differential effects of soybean and fenugreek extracts on the growth of MCF-7 cells. Chem Biol Interact 2007; 170(2): 135-43. google scholar
  • 21. Al-Oqail MM, Farshori NN, Al-Sheddi ES, Musarrat J, Al-Khedhairy AA, Siddiqui M A. In vitro cytotoxic activity of seed oil of fenugreek against various cancer cell lines. Asian Pac J Cancer Prev 2013; 14(3): 1829-32. google scholar
  • 22. Liu A, Chen S, Cai S, Dong L, Liu L, Yang Y, et al. Wnt5a through noncanonical Wnt/JNK or Wnt/PKC signaling contributes to the differentiation of mesenchymal stem cells into type II alveolar epithelial cells in vitro. PLoS One 2014: 9(3): e90229. google scholar
  • 23. Chen C, Shi Y, Ma J, Chen Z, Zhang Mi Zhao Y. Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway. Diabetol Metab Syndr 2022; 14(1): 28. google scholar
  • 24. Tewari D, Jóźwik A, Łysek-Gładysińska M, Grzybek W, Bialek WA, Bicki J, et al. Fenugreek (Trigonella foenum-graecum L.) seeds dietary supplementation regulates liver antioxidant defense systems in aging mice. Nutrients 2020; 12(9): 2552. google scholar
  • 25. Pandurangan AK, Dharmalingam P, Sadagopan SKA, Ramar M, Munusamy A. Luteolin induces growth arrest in colon cancer cells through involvement of Wnt/β-catenin/GSK-3β signaling. J Environ Pathol Toxicol Oncol 2013; 32(2): 131-9 google scholar
  • 26. Ashokkumar P, Sudhandiran G. Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/β-catenin pathway. Invest New Drugs 2011; 29: 273-84. google scholar
  • 27. Wang B, Wang S, Ding M, Lu H, Wu H, Li Y. Quercetin regulates calcium and phosphorus metabolism through the Wnt signaling pathway in broilers. Front Vet Sci 2022; 8: 786519. google scholar
  • 28. Kim H, Seo EM, Sharma AR, Ganbold B, Park J, Sharma G, et al. Regulation of Wnt signaling activity for growth suppression induced by quercetin in 4T1 murine mammary cancer cells. Int J Oncol 2013; 43(4): 1319-25. google scholar
  • 29. Yao H, Ashihara E, Maekawa T. Targeting the Wnt/β-catenin signaling pathway in human cancers. Expert Opin Ther Targets 2011; 15(7): 873-87. google scholar
  • 30. Zhou J, Tian H, Zhi X, Xiao Z, Chen T, Yuan H, et al. Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer. Cancer Cell Int 2021; 21(1): 660. google scholar
  • 31. Pepe F, Bill M, Papaioannou D, Karunasiri M, Walker A, Naumann E, et al. Targeting Wnt signaling in acute myeloid leukemia stem cells. Haematologica 2022; 107(1): 307-11. google scholar
  • 32. Mencalha AL, Corrêa S, Abdelhay E. Role of calcium-dependent protein kinases in chronic myeloid leukemia: combined effects of PKC and BCR-ABL signaling on cellular alterations during leukemia development. Onco Targets Ther 2014; 7: 1247-54. google scholar
  • 33. Robert G, Ben Sahra I, Puissant A, Colosetti P, Belhacene, Gounon P, et al. Acadesine kills chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death. PloS one 2009; 4(11): e7889. google scholar
  • 34. Cui C, Wang C, Cao M, Kang X. Ca2+/calmodulin-dependent protein kinases in leukemia development. J Cell Immunol 2021; 3(3): 144-50 google scholar
  • 35. Na YJ, Yu ES, Kim DS, Lee DH, Oh SC, Choi CW. Metformin enhances the cytotoxic effect of nilotinib and overcomes nilotinib resistance in chronic myeloid leukemia cells. Korean J Intern Med 2021; 36: 196-206 google scholar

Cytotoxic Effect of Fenugreek (Trigonella foenum-graecum) Seed Extracts on the Wnt Signaling Pathway in the K562 Cell Line

Year 2025, Volume: 15 Issue: 2, 169 - 174, 29.08.2025
https://doi.org/10.26650/experimed.1591042

Abstract

Objective: Researchers have established that the fenugreek plant exhibits anti-proliferative effects against various types of cancer, highlighting its potential as a valuable source for the development of new anticancer drugs. This study attempted to assess the anti-cancer effects of fenugreek on the K562 chronic myeloid leukemia (CML) cells due to the Wnt signaling pathway.

Materials and Methods: The cytotoxic effect of Fenugreek was performed by 2,3-bis(2-methoxy-4-nitro-5 sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. We used reverse transcription-polymerase chain reaction (RT-PCR) to determine gene expression, and western blot was used to detect β-catenin, c-Jun N terminal kinase (JNK), calcium/calmodulin-dependent protein kinase (CamK), and protein kinase C (PKC) proteins.

Results: The IC₅₀ value of fenugreek extract was 717 g/mL after 24 h, and an in vitro cytotoxic effect was observed on K562 cell lines. JNK, PKC, CamK, and β-catenin protein levels were reduced in fenugreek extract-treated cells by 81%, 20%, 7%, and 26%, respectively.

Conclusion: According to our findings, fenugreek can affect both canonical and non-canonical pathways in K562 cells, particularly via the JNK protein in the planar cell polarity (PCP) pathway. These data corroborates our hypothesis that fenugreek extract possesses adjuvant compounds beneficial for CML treatment.

Project Number

1919B012004879

References

  • 1. Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol 2021; 14(1): 44. google scholar
  • 2. Braun TP, Eide CA, Druker BJ. Response and resistance to BCR-ABL1-targeted therapies. Cancer Cell 2020; 37(4): 530-42. google scholar
  • 3. Grassi S, Palumbo S, Mariotti V, Liberati D, Guerrini F, Ciabatti E, et al. The WNT pathway is relevant for the BCR-ABL1-independent resistance in chronic myeloid leukemia. Front Oncol 2019; 9: 532. google scholar
  • 4. Chiarini F, Paganelli F, Martelli AM, Evangelisti C. The role played by Wnt/β-catenin signaling pathway in acute lymphoblastic leukemia. Int J Mol Sci 2020; 21(3): 1098. google scholar
  • 5. Khan F, Negi K, Kumar T. Effect of sprouted fenugreek seeds on various diseases: A review. J. Diabetes Metab Disord Control 2018; 5: 119-125. google scholar
  • 6. Ahmad A, Alghamdi SS, Mahmood K, Afzal M. Fenugreek a multipurpose crop: potentialities and improvements. Saudi J Biol Sci 2016; 23(2): 300-10. google scholar
  • 7. Shabbeer S, Sobolewski M, Anchoori RK, Kachhap S, Hidalgo M, Jimeno A, et al. Fenugreek: a naturally occurring edible spice as an anticancer agent. Cancer Biol Ther 2009; 8(3): 272-78. google scholar
  • 8. Müschen M. WNT/β-Catenin Signaling in Leukemia. In: Goss K, Kahn M. (eds) Targeting the Wnt pathway in cancer. Springer, New York, NY. 2011. p.129–42. google scholar
  • 9. Pehlivan M, Soyoz M, Cerci B, Karahan Coven HI, Yuce Z, Sercan, H. sFRP1 expression induces miRNAs that modulate Wnt signaling in chronic myeloid leukemia cells. Mol Biol 2020; 54(4): 626-33. google scholar
  • 10. Bavaro L, Martelli M, Cavo M, Soverini S. Mechanisms of disease progression and resistance to tyrosine kinase inhibitor therapy in chronic myeloid leukemia: an update. Int J Mol Sci 2019; 20(24): 6141. google scholar
  • 11. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990; 44(4): 301-6. google scholar
  • 12. Losso JN, Holliday DL, Finley JW, Martin RJ, Rood JC, Yu Y, et al. Fenugreek bread: a treatment for diabetes mellitus. J Med Food 2009; 12(5): 1046-49. google scholar
  • 13. Pandian RS, Anuradha CV, Viswanathan P. Gastroprotective effect of fenugreek seeds (Trigonella foenum graecum) on experimental gastric ulcer in rats. J Ethnopharmacol 2002; 81(3): 393-97. google scholar
  • 14. Uemura T, Hirai S, Mizoguchi N, Goto T, Lee JY, Taketani K, et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. Mol Nutr Food Res 2010; 54(11): 1596-608. google scholar
  • 15. Chaudhary S, Chaudhary PS, Chikara SK, Sharma MC, Iriti M. Review on fenugreek (Trigonella foenum-graecum L.) and its important secondary metabolite diosgenin. Not Bot Horti Agrobot Cluj‑Napoca 2018; 46(1): 22-31. google scholar
  • 16. Alsemari A, Alkhodairy F, Aldakan A, Hohanna MA, Bahoush E, Shinwari Z, et al. The selective cytotoxic anti-cancer properties and proteomic analysis of Trigonella Foenum-Graecum. BMC Complement Med Ther 2014; 14: 114. google scholar
  • 17. Khalil MI, Ibrahim MM, El-Gaaly GA, Sultan AS. Trigonella foenum (Fenugreek) induced apoptosis in hepatocellular carcinoma cell line, HepG2, mediated by upregulation of p53 and proliferating cell nuclear antigen. BioMed Res Int 2015; 2015: 914645. google scholar
  • 18. Alshatwi AA, Shafi G, Hasan TN, Syed NA, Khoja KK. Fenugreek induced apoptosis in breast cancer MCF-7 cells mediated independently by Fas receptor change. Asian Pac J Cancer Prev 2013; 14(10): 5783-8. google scholar
  • 19. Khoja KK, Howes MJR, Hider R, Sharp PA, Farrell IW, Latunde-Dada GO. Cytotoxicity of fenugreek sprout and seed extracts and their bioactive constituents on MCF-7 breast cancer cells. Nutrients 2022; 14(4): 784. google scholar
  • 20. Sebastian KS, Thampan RV. Differential effects of soybean and fenugreek extracts on the growth of MCF-7 cells. Chem Biol Interact 2007; 170(2): 135-43. google scholar
  • 21. Al-Oqail MM, Farshori NN, Al-Sheddi ES, Musarrat J, Al-Khedhairy AA, Siddiqui M A. In vitro cytotoxic activity of seed oil of fenugreek against various cancer cell lines. Asian Pac J Cancer Prev 2013; 14(3): 1829-32. google scholar
  • 22. Liu A, Chen S, Cai S, Dong L, Liu L, Yang Y, et al. Wnt5a through noncanonical Wnt/JNK or Wnt/PKC signaling contributes to the differentiation of mesenchymal stem cells into type II alveolar epithelial cells in vitro. PLoS One 2014: 9(3): e90229. google scholar
  • 23. Chen C, Shi Y, Ma J, Chen Z, Zhang Mi Zhao Y. Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway. Diabetol Metab Syndr 2022; 14(1): 28. google scholar
  • 24. Tewari D, Jóźwik A, Łysek-Gładysińska M, Grzybek W, Bialek WA, Bicki J, et al. Fenugreek (Trigonella foenum-graecum L.) seeds dietary supplementation regulates liver antioxidant defense systems in aging mice. Nutrients 2020; 12(9): 2552. google scholar
  • 25. Pandurangan AK, Dharmalingam P, Sadagopan SKA, Ramar M, Munusamy A. Luteolin induces growth arrest in colon cancer cells through involvement of Wnt/β-catenin/GSK-3β signaling. J Environ Pathol Toxicol Oncol 2013; 32(2): 131-9 google scholar
  • 26. Ashokkumar P, Sudhandiran G. Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/β-catenin pathway. Invest New Drugs 2011; 29: 273-84. google scholar
  • 27. Wang B, Wang S, Ding M, Lu H, Wu H, Li Y. Quercetin regulates calcium and phosphorus metabolism through the Wnt signaling pathway in broilers. Front Vet Sci 2022; 8: 786519. google scholar
  • 28. Kim H, Seo EM, Sharma AR, Ganbold B, Park J, Sharma G, et al. Regulation of Wnt signaling activity for growth suppression induced by quercetin in 4T1 murine mammary cancer cells. Int J Oncol 2013; 43(4): 1319-25. google scholar
  • 29. Yao H, Ashihara E, Maekawa T. Targeting the Wnt/β-catenin signaling pathway in human cancers. Expert Opin Ther Targets 2011; 15(7): 873-87. google scholar
  • 30. Zhou J, Tian H, Zhi X, Xiao Z, Chen T, Yuan H, et al. Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer. Cancer Cell Int 2021; 21(1): 660. google scholar
  • 31. Pepe F, Bill M, Papaioannou D, Karunasiri M, Walker A, Naumann E, et al. Targeting Wnt signaling in acute myeloid leukemia stem cells. Haematologica 2022; 107(1): 307-11. google scholar
  • 32. Mencalha AL, Corrêa S, Abdelhay E. Role of calcium-dependent protein kinases in chronic myeloid leukemia: combined effects of PKC and BCR-ABL signaling on cellular alterations during leukemia development. Onco Targets Ther 2014; 7: 1247-54. google scholar
  • 33. Robert G, Ben Sahra I, Puissant A, Colosetti P, Belhacene, Gounon P, et al. Acadesine kills chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death. PloS one 2009; 4(11): e7889. google scholar
  • 34. Cui C, Wang C, Cao M, Kang X. Ca2+/calmodulin-dependent protein kinases in leukemia development. J Cell Immunol 2021; 3(3): 144-50 google scholar
  • 35. Na YJ, Yu ES, Kim DS, Lee DH, Oh SC, Choi CW. Metformin enhances the cytotoxic effect of nilotinib and overcomes nilotinib resistance in chronic myeloid leukemia cells. Korean J Intern Med 2021; 36: 196-206 google scholar
There are 35 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Article
Authors

Can Vuruşkan 0000-0003-1266-9898

Burcu Çerçi Alkaç 0000-0002-7477-1073

Tuba Oz 0000-0003-4366-8927

Melek Pehlivan 0000-0001-8755-4812

Mustafa Soyöz 0000-0001-5159-6463

Project Number 1919B012004879
Publication Date August 29, 2025
Submission Date November 28, 2024
Acceptance Date June 18, 2025
Published in Issue Year 2025 Volume: 15 Issue: 2

Cite

Vancouver Vuruşkan C, Çerçi Alkaç B, Oz T, Pehlivan M, Soyöz M. Cytotoxic Effect of Fenugreek (Trigonella foenum-graecum) Seed Extracts on the Wnt Signaling Pathway in the K562 Cell Line. Experimed. 2025;15(2):169-74.