Ellagic Acid Ameliorates Ovarian Cancer via Modification of Pyroptosis and Inflammation
Abstract
Ovarian cancer is 1 of the most serious female malignancies worldwide. Despite intensive efforts to overcome ovarian cancer, there remain limited treatment options for this disease. Ellagic acid (EA), a well-known phytochemical with anti-inflammatory properties, is suggested as a therapeutical strategy as it can inhibit the growth of certain cancer cells. However, its effect on human ovarian carcinoma cells has not yet been fully elucidated. The present study aimed to explore the effect of EA on ovarian carcinoma and further expound the underlying mechanisms of EA-induced ovarian cancer cell death.
Human ovarian carcinoma cell lines, A2780 and OVCAR3, were treated with EA (0, 10, 20, 50, and 100 μM) and assessed for viability, cell cycle (cyclin D1 and cyclin E), pyroptosis (gasdermin D [GSDMD] and gasdermin E [GSDME]), autophagy (microtubule-associated protein 1A/1B-light chain 3 [MAP1LC3] and autophagy protein 5 [ATG5]), and inflammation (interleukin [IL]-1b and IL-6) via 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA).
The findings showed that EA could significantly inhibit cell viability, decrease cyclin D1 and E levels, downregulate GSDMD and GSDME, and suppress the levels of inflammatory markers, including IL-1b and IL-6. However, the protein levels of autophagic markers including LC3 and ATG5 remained mostly unchanged.
The findings suggest that EA could suppress ovarian cancer cell viability and proliferation by arresting both cell lines at the G1 phase of the cell cycle through modification of cell death mediated by inflammatory-caused pyroptosis.
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2. Lumish MA, Kohn EC, Tew WP. Top advances of the year: Ovarian cancer. Cancer. 2024;15;130(6):837-845.
3. Stewart C, Ralyea C, Lockwood S, editors. Ovarian cancer: an integrated review. Semin Oncol Nurs. 2019: Elsevier.
4. Feeney L, Harley IJ, McCluggage WG, Mullan PB, Beirne JP. Liquid biopsy in ovarian cancer: Catching the silent killer before it strikes. World J Clin Oncol. 2020;11(11):868.
5. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health. 2019:287-99.
6. MORI M, HARABUCHI I, MIYAKE H, CASAGRANDE JT, HENDERSON BE, ROSS RK. Reproductive, genetic, and dietary risk factors for ovarian cancer. Am J Epidemiol. 1988;128(4):771-7.
7. Zhang R, Chen J, Mao L, Guo Y, Hao Y, Deng Y et al. Nobiletin triggers reactive oxygen species-mediated pyroptosis through regulating autophagy in ovarian cancer cells. J Agric Food Chem. 2020;68(5):1326-36.
8. Qiao L, Wu X, Zhang J, Liu L, Sui X, Zhang R et al. α‐NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase‐4 pathway. FASEB J. 2019;33(11):12760-7.
9. Shen Y, Li D-D, Wang L-L, Deng R, Zhu X-F. Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy. 2008;4(8):1067-8.
10. Browning L, Patel MR, Horvath EB, Tawara K, Jorcyk CL. IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis. Cancer Manag Res. 2018:6685-93.
11. Olson SH, Mignone L, Nakraseive C, Caputo T, Barakat R, Harlap S. Symptoms of ovarian cancer. Obstet Gynecol. 2001;98(2):212-7.
12. Goff B. Symptoms associated with ovarian cancer. Clin Obstet Gynecol. 2012;55(1):36-42.
13. Deraco M, Baratti D, Laterza B, Balestra M, Mingrone E, Macrì A et al. Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Europ J Surgical Oncol. 2011;37(1):4-9.
14. Gomez-Raposo C, Mendiola M, Barriuso J, Hardisson D, Redondo A. Molecular characterization of ovarian cancer by gene-expression profiling. Gynecologic Oncol. 2010;118(1):88-92.
15. Cohen M, Dromard M, Petignat P. Heat shock proteins in ovarian cancer: a potential target for therapy. Gynecol Oncol. 2010;119(1):164-6.
16. Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R. Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay. Anticancer Res. 2001;21(6A):3903-8.
17. Vattem D, Shetty K. Biological functionality of ellagic acid: a review. J Food Biochem. 2005;29(3):234-66.
18. Losso JN, Bansode RR, Trappey II A, Bawadi HA, Truax R. In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem. 2004;15(11):672-8.
19. Das U, Biswas S, Chattopadhyay S, Chakraborty A, Dey Sharma R, Banerji A, Dey S. Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study. Sci Rep. 2017;25;7(1):14043.
20. Sharifi-Rad J, Quispe C, Castillo CMS, Caroca R, Lazo-Vélez MA, Antonyak H et al. Ellagic acid: A review on its natural sources, chemical stability, and therapeutic potential. Oxid Med Cell Longev. 2022;2022.
21. Mohammadinejad A, Mohajeri T, Aleyaghoob G, Heidarian F, Kazemi Oskuee R. Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies. Biotechnol Appl Biochem. 2022;69(6):2323-56.
22. Kim JY, Choi YJ, Kim H-J. Determining the effect of ellagic acid on the proliferation and migration of pancreatic cancer cell lines. Trans Cancer Res. 2021;10(1):424.
23. Ni X, Shang FS, Wang TF, Wu DJ, Chen DG, Zhuang B. Ellagic acid induces apoptosis and autophagy in colon cancer through the AMPK/mTOR pathway. Tissue Cell. 2023;81:102032.
24. Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y et al. Drug resistance in ovarian cancer: from mechanism to clinical trial. Mol Cancer. 2024;23(1):66.
25. Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 2020;96:316-26.
26. Liu Y, Han S, Li Y, Liu Y, Zhang D, Li Y et al. MicroRNA-20a contributes to cisplatin-resistance and migration of OVCAR3 ovarian cancer cell line. Oncol lett. 2017;14(2):1780-6.
27. Zheng AW, Chen YQ, Zhao LQ, Feng JG. Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells. Oncol lett. 2017;13(6):4974-8.
28. Chung YC, Lu LC, Tsai MH, Chen YJ, Chen YY, Yao SP, Hsu CP. The inhibitory effect of ellagic Acid on cell growth of ovarian carcinoma cells. Evid Based Complement Alternat Med. 2013;2013:306705. doi: 10.1155/2013/306705. Epub 2013 Jun 16. PMID: 23843871; PMCID: PMC3697306.
29. Liu X, Zuo X, Sun X, Tian X, Teng Y. Hexokinase 2 Promotes Cell Proliferation and Tumor Formation through the Wnt/β-catenin Pathway-mediated Cyclin D1/c-myc Upregulation in Epithelial Ovarian Cancer. J Cancer. 2022;13(8):2559-69.
30. Sharma A, Liu X, Chandra V, Rai R, Benbrook DM, Woo S. Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing. AAPS J. 2023;26(1):5.
31. Zuo Y, Zheng W, Tang Q, Liu J, Wang S, Xin C. miR‑576‑3p overexpression enhances cisplatin sensitivity of ovarian cancer cells by dysregulating PD‑L1 and cyclin D1. Mol Med Rep. 2021;23(1):1-.
32. Chu C, Geng Y, Zhou Y, Sicinski P. Cyclin E in normal physiology and disease states. Trends Cell Biol. 2021;31(9):732-46.
33. Pang W, Li Y, Guo W, Shen H. Cyclin E: a potential treatment target to reverse cancer chemoresistance by regulating the cell cycle. Am J Trans Res. 2020;12(9):5170.
34. Duman-Scheel M, Weng L, Xin S, Du W. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature. 2002;417(6886):299-304.
35. Loden M, Stighall M, Nielsen NH, Roos G, Emdin SO, Östlund H et al. The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node. Oncogene. 2002;21(30):4680-90.
36. Catanzaro D, Ragazzi E, Vianello C, Caparrotta L, Montopoli M. Effect of quercetin on cell cycle and cyclin expression in ovarian carcinoma and osteosarcoma cell lines. Nat Prod Commun. 2015;10(8):
1934578X1501000813.
37. Vergara D, Simeone P, Toraldo D, Del Boccio P, Vergaro V, Leporatti S et al. Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Molr Bio. 2012;8(4):1078-87.
38. Samare-Najaf M, Samareh A, Savardashtaki A, Khajehyar N, Tajbakhsh A, Vakili S et al. Non-Apoptotic Cell Death Programs in Cervical Cancer with an Emphasis on Ferroptosis. Cell Prolif. 2023:104249.
39. Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci. 2021;22(1):426.
40. Berkel C, Cacan E. Differential expression and copy number variation of gasdermin (GSDM) family members, pore-forming proteins in pyroptosis, in normal and malignant serous ovarian tissue. Inflammation. 2021;44(6):2203-16.
41. Wang S, Liu Y, Xiao H, Chen Z, Yang X, Yin J et al. Inhibition of SF3B1 improves the immune microenvironment through pyroptosis and synergizes with αPDL1 in ovarian cancer. Cell Death Dis. 2023;14(11):775.
42. Wang X, Yin Y, Qian W, Peng C, Shen S, Wang T et al. Citric acid of ovarian cancer metabolite induces pyroptosis via the caspase‐4/TXNIP‐NLRP3‐GSDMD pathway in ovarian cancer. FASEB J. 2022;36(6):e22362.
43. Berkel C, Cacan E. Lower expression of NINJ1 (Ninjurin 1), a mediator of plasma membrane rupture, is associated with advanced disease and worse prognosis in serous ovarian cancer. Immunol Res. 2023;71(1):15-28.
44. Wang J, Wu GS. Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem. 2014;289(24):17163-73.
45. Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R et al. Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. BioMed research international. 2014;2014.
46. Xie Z, Guo Z, Wang Y, Lei J, Yu J. Protocatechuic acid inhibits the growth of ovarian cancer cells by inducing apoptosis and autophagy. Phytother Res. 2018;32(11):2256-63.
47. Zhou J, Jiang Yy, Chen H, Wu Yc, Zhang L. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Prolif. 2020;53(2):e12739.
48. Klapp V, Álvarez-Abril B, Leuzzi G, Kroemer G, Ciccia A, Galluzzi L. The DNA damage response and inflammation in cancer. Cancer Discovery. 2023;13(7):1521-45.
49. Khandia R, Munjal A. Interplay between inflammation and cancer. Adv Protein Chem Struct Biol. 2020;119:199-245.
50. Macciò A, Madeddu C. Inflammation and ovarian cancer. Cytokine. 2012;58(2):133-47.
51. Savant SS, Sriramkumar S, O’Hagan HM. The role of inflammation and inflammatory mediators in the development, progression, metastasis, and chemoresistance of epithelial ovarian cancer. Cancers. 2018;10(8):251.
52. Xu X-L, Deng S-L, Lian Z-X, Yu K. Resveratrol targets a variety of oncogenic and oncosuppressive signaling for ovarian cancer prevention and treatment. Antioxidants. 2021;10(11):1718.
53. Elsaid FG, Alshehri MA, Shati AA, Al‐Kahtani MA, Alsheri AS, Massoud EE et al. The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK. Clin Exp Pharmacol Physiol. 2020;47(9):1611-21.
54. Dhanaraj T, Mohan M, Arunakaran J. Quercetin attenuates metastatic ability of human metastatic ovarian cancer cells via modulating multiple signaling molecules involved in cell survival, proliferation, migration and adhesion. Arch Biochem Biophysics. 2021;701:108795.
2. Lumish MA, Kohn EC, Tew WP. Top advances of the year: Ovarian cancer. Cancer. 2024;15;130(6):837-845.
3. Stewart C, Ralyea C, Lockwood S, editors. Ovarian cancer: an integrated review. Semin Oncol Nurs. 2019: Elsevier.
4. Feeney L, Harley IJ, McCluggage WG, Mullan PB, Beirne JP. Liquid biopsy in ovarian cancer: Catching the silent killer before it strikes. World J Clin Oncol. 2020;11(11):868.
5. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health. 2019:287-99.
6. MORI M, HARABUCHI I, MIYAKE H, CASAGRANDE JT, HENDERSON BE, ROSS RK. Reproductive, genetic, and dietary risk factors for ovarian cancer. Am J Epidemiol. 1988;128(4):771-7.
7. Zhang R, Chen J, Mao L, Guo Y, Hao Y, Deng Y et al. Nobiletin triggers reactive oxygen species-mediated pyroptosis through regulating autophagy in ovarian cancer cells. J Agric Food Chem. 2020;68(5):1326-36.
8. Qiao L, Wu X, Zhang J, Liu L, Sui X, Zhang R et al. α‐NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase‐4 pathway. FASEB J. 2019;33(11):12760-7.
9. Shen Y, Li D-D, Wang L-L, Deng R, Zhu X-F. Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy. 2008;4(8):1067-8.
10. Browning L, Patel MR, Horvath EB, Tawara K, Jorcyk CL. IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis. Cancer Manag Res. 2018:6685-93.
11. Olson SH, Mignone L, Nakraseive C, Caputo T, Barakat R, Harlap S. Symptoms of ovarian cancer. Obstet Gynecol. 2001;98(2):212-7.
12. Goff B. Symptoms associated with ovarian cancer. Clin Obstet Gynecol. 2012;55(1):36-42.
13. Deraco M, Baratti D, Laterza B, Balestra M, Mingrone E, Macrì A et al. Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Europ J Surgical Oncol. 2011;37(1):4-9.
14. Gomez-Raposo C, Mendiola M, Barriuso J, Hardisson D, Redondo A. Molecular characterization of ovarian cancer by gene-expression profiling. Gynecologic Oncol. 2010;118(1):88-92.
15. Cohen M, Dromard M, Petignat P. Heat shock proteins in ovarian cancer: a potential target for therapy. Gynecol Oncol. 2010;119(1):164-6.
16. Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R. Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay. Anticancer Res. 2001;21(6A):3903-8.
17. Vattem D, Shetty K. Biological functionality of ellagic acid: a review. J Food Biochem. 2005;29(3):234-66.
18. Losso JN, Bansode RR, Trappey II A, Bawadi HA, Truax R. In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem. 2004;15(11):672-8.
19. Das U, Biswas S, Chattopadhyay S, Chakraborty A, Dey Sharma R, Banerji A, Dey S. Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study. Sci Rep. 2017;25;7(1):14043.
20. Sharifi-Rad J, Quispe C, Castillo CMS, Caroca R, Lazo-Vélez MA, Antonyak H et al. Ellagic acid: A review on its natural sources, chemical stability, and therapeutic potential. Oxid Med Cell Longev. 2022;2022.
21. Mohammadinejad A, Mohajeri T, Aleyaghoob G, Heidarian F, Kazemi Oskuee R. Ellagic acid as a potent anticancer drug: A comprehensive review on in vitro, in vivo, in silico, and drug delivery studies. Biotechnol Appl Biochem. 2022;69(6):2323-56.
22. Kim JY, Choi YJ, Kim H-J. Determining the effect of ellagic acid on the proliferation and migration of pancreatic cancer cell lines. Trans Cancer Res. 2021;10(1):424.
23. Ni X, Shang FS, Wang TF, Wu DJ, Chen DG, Zhuang B. Ellagic acid induces apoptosis and autophagy in colon cancer through the AMPK/mTOR pathway. Tissue Cell. 2023;81:102032.
24. Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y et al. Drug resistance in ovarian cancer: from mechanism to clinical trial. Mol Cancer. 2024;23(1):66.
25. Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 2020;96:316-26.
26. Liu Y, Han S, Li Y, Liu Y, Zhang D, Li Y et al. MicroRNA-20a contributes to cisplatin-resistance and migration of OVCAR3 ovarian cancer cell line. Oncol lett. 2017;14(2):1780-6.
27. Zheng AW, Chen YQ, Zhao LQ, Feng JG. Myricetin induces apoptosis and enhances chemosensitivity in ovarian cancer cells. Oncol lett. 2017;13(6):4974-8.
28. Chung YC, Lu LC, Tsai MH, Chen YJ, Chen YY, Yao SP, Hsu CP. The inhibitory effect of ellagic Acid on cell growth of ovarian carcinoma cells. Evid Based Complement Alternat Med. 2013;2013:306705. doi: 10.1155/2013/306705. Epub 2013 Jun 16. PMID: 23843871; PMCID: PMC3697306.
29. Liu X, Zuo X, Sun X, Tian X, Teng Y. Hexokinase 2 Promotes Cell Proliferation and Tumor Formation through the Wnt/β-catenin Pathway-mediated Cyclin D1/c-myc Upregulation in Epithelial Ovarian Cancer. J Cancer. 2022;13(8):2559-69.
30. Sharma A, Liu X, Chandra V, Rai R, Benbrook DM, Woo S. Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing. AAPS J. 2023;26(1):5.
31. Zuo Y, Zheng W, Tang Q, Liu J, Wang S, Xin C. miR‑576‑3p overexpression enhances cisplatin sensitivity of ovarian cancer cells by dysregulating PD‑L1 and cyclin D1. Mol Med Rep. 2021;23(1):1-.
32. Chu C, Geng Y, Zhou Y, Sicinski P. Cyclin E in normal physiology and disease states. Trends Cell Biol. 2021;31(9):732-46.
33. Pang W, Li Y, Guo W, Shen H. Cyclin E: a potential treatment target to reverse cancer chemoresistance by regulating the cell cycle. Am J Trans Res. 2020;12(9):5170.
34. Duman-Scheel M, Weng L, Xin S, Du W. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature. 2002;417(6886):299-304.
35. Loden M, Stighall M, Nielsen NH, Roos G, Emdin SO, Östlund H et al. The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node. Oncogene. 2002;21(30):4680-90.
36. Catanzaro D, Ragazzi E, Vianello C, Caparrotta L, Montopoli M. Effect of quercetin on cell cycle and cyclin expression in ovarian carcinoma and osteosarcoma cell lines. Nat Prod Commun. 2015;10(8):
1934578X1501000813.
37. Vergara D, Simeone P, Toraldo D, Del Boccio P, Vergaro V, Leporatti S et al. Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Molr Bio. 2012;8(4):1078-87.
38. Samare-Najaf M, Samareh A, Savardashtaki A, Khajehyar N, Tajbakhsh A, Vakili S et al. Non-Apoptotic Cell Death Programs in Cervical Cancer with an Emphasis on Ferroptosis. Cell Prolif. 2023:104249.
39. Tsuchiya K. Switching from apoptosis to pyroptosis: gasdermin-elicited inflammation and antitumor immunity. Int J Mol Sci. 2021;22(1):426.
40. Berkel C, Cacan E. Differential expression and copy number variation of gasdermin (GSDM) family members, pore-forming proteins in pyroptosis, in normal and malignant serous ovarian tissue. Inflammation. 2021;44(6):2203-16.
41. Wang S, Liu Y, Xiao H, Chen Z, Yang X, Yin J et al. Inhibition of SF3B1 improves the immune microenvironment through pyroptosis and synergizes with αPDL1 in ovarian cancer. Cell Death Dis. 2023;14(11):775.
42. Wang X, Yin Y, Qian W, Peng C, Shen S, Wang T et al. Citric acid of ovarian cancer metabolite induces pyroptosis via the caspase‐4/TXNIP‐NLRP3‐GSDMD pathway in ovarian cancer. FASEB J. 2022;36(6):e22362.
43. Berkel C, Cacan E. Lower expression of NINJ1 (Ninjurin 1), a mediator of plasma membrane rupture, is associated with advanced disease and worse prognosis in serous ovarian cancer. Immunol Res. 2023;71(1):15-28.
44. Wang J, Wu GS. Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem. 2014;289(24):17163-73.
45. Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R et al. Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. BioMed research international. 2014;2014.
46. Xie Z, Guo Z, Wang Y, Lei J, Yu J. Protocatechuic acid inhibits the growth of ovarian cancer cells by inducing apoptosis and autophagy. Phytother Res. 2018;32(11):2256-63.
47. Zhou J, Jiang Yy, Chen H, Wu Yc, Zhang L. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Prolif. 2020;53(2):e12739.
48. Klapp V, Álvarez-Abril B, Leuzzi G, Kroemer G, Ciccia A, Galluzzi L. The DNA damage response and inflammation in cancer. Cancer Discovery. 2023;13(7):1521-45.
49. Khandia R, Munjal A. Interplay between inflammation and cancer. Adv Protein Chem Struct Biol. 2020;119:199-245.
50. Macciò A, Madeddu C. Inflammation and ovarian cancer. Cytokine. 2012;58(2):133-47.
51. Savant SS, Sriramkumar S, O’Hagan HM. The role of inflammation and inflammatory mediators in the development, progression, metastasis, and chemoresistance of epithelial ovarian cancer. Cancers. 2018;10(8):251.
52. Xu X-L, Deng S-L, Lian Z-X, Yu K. Resveratrol targets a variety of oncogenic and oncosuppressive signaling for ovarian cancer prevention and treatment. Antioxidants. 2021;10(11):1718.
53. Elsaid FG, Alshehri MA, Shati AA, Al‐Kahtani MA, Alsheri AS, Massoud EE et al. The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK. Clin Exp Pharmacol Physiol. 2020;47(9):1611-21.
54. Dhanaraj T, Mohan M, Arunakaran J. Quercetin attenuates metastatic ability of human metastatic ovarian cancer cells via modulating multiple signaling molecules involved in cell survival, proliferation, migration and adhesion. Arch Biochem Biophysics. 2021;701:108795.
| Files | ||
| Issue | Vol 24 No 1 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v24i1.18025 | |
| Keywords | ||
| Autophagy Ellagic acid Cell cycle Inflammation Pyroptosis Ovarian cancer | ||
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How to Cite
1.
Sun Y, Hu X, Wang Y. Ellagic Acid Ameliorates Ovarian Cancer via Modification of Pyroptosis and Inflammation. Iran J Allergy Asthma Immunol. 2025;24(1):100-114.
