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Year 2025, Volume: 15 Issue: 3, 629 - 635, 30.09.2025

Saime Batırel , Bengü Çetinkaya , Ayşe Mine Yılmaz

https://doi.org/10.33808/clinexphealthsci.1646378

Abstract

References

  • Lander S, Lander E, Gibson MK. Esophageal cancer: Overview, risk factors, and reasons for the rise. Curr Gastroenterol Rep. 2023;25(11):275-279. https://doi.org/10.1007/s11894-023-00899-0.
  • Due SL, Watson DI, Hussey DJ. Oestrogen receptors: A potential therapeutic target in oesophageal adenocarcinoma? ANZ J Surg. 2021;91(7-8):1390-1396. https://doi.org/10.1111/ans.17054.
  • Jiang Z, Chen K, Cheng L, Yan B, Qian W, Cao J, Li J, Wu E, Ma Q, Yang W. Resveratrol and cancer treatment: updates. Ann N Y Acad Sci. 2017;1403(1):59-69. https://doi.org/10.1111/nyas.13466.
  • Petrick JL, Steck SE, Bradshaw PT, Trivers KF, Abrahamson PE, Engel LS, He K, Chow WH, Mayne ST, Risch HA, Vaughan TL, Gammon MD. Dietary intake of flavonoids and oesophageal and gastric cancer: Incidence and survival in the United States of America (USA). Br J Cancer. 2015;112(7):1291-300. https://doi.org/10.1038/bjc.2015.25.
  • Jin Z, Feng W, Ji Y, Jin L. Resveratrol mediates cell cycle arrest and cell death in human esophageal squamous cell carcinoma by directly targeting the EGFR signaling pathway. Oncol Lett. 2017;13(1):347-355. https://doi.org/10.3892/ol.2016.5391.
  • Baek SH, Ko JH, Lee H, Jung J, Kong M, Lee JW, Lee J, Chinnathambi A, Zayed ME, Alharbi SA, Lee SG, Shim BS, Sethi G, Kim SH, Yang WM, Um JY, Ahn KS. Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: Role in apoptosis induction and radiosensitization in head and neck tumor cells. Phytomedicine. 2016;23(5):566-77. https://doi.org/10.1016/j.phymed.2016.02.011.
  • Harikumar KB, Kunnumakkara AB, Sethi G, Diagaradjane P, Anand P, Pandey MK, Gelovani J, Krishnan S, Guha S, Aggarwal BB. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010;127(2):257-68. https://doi.org/10.1002/ijc.25041.
  • Lin Y, Yngve A, Lagergren J, Lu Y. A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer. Br J Nutr. 2014;112(12):2002-9. https://doi.org/10.1017/S0007114514003055.
  • Zhou HB, Yan Y, Sun YN, Zhu JR. Resveratrol induces apoptosis in human esophageal carcinoma cells. World J Gastroenterol. 2003;9(3):408-11. https://doi.org/10.3748/wjg.v9.i3.408.
  • Klingelhöfer D, Zhu Y, Braun M, Brüggmann D, Schöffel N, Groneberg DA. A world map of esophagus cancer research: a critical accounting. J Transl Med. 2019;17(1):150. https://doi.org/10.1186/s12967-019-1902-7.
  • Chung MY, Lim TG, Lee KW. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development. World J Gastroenterol. 2013;19(7):984-93. https://doi.org/10.3748/wjg.v19.i7.984.
  • Cione E, La Torre C, Cannataro R, Caroleo MC, Plastina P, Gallelli L. Quercetin, epigallocatechin gallate, curcumin, and resveratrol: From dietary sources to human microrna modulation. Molecules. 2019;25(1):63. https://doi.org/10.3390/molecules25010063.
  • Berretta M, Bignucolo A, Di Francia R, Comello F, Facchini G, Ceccarelli M, Iaffaioli RV, Quagliariello V, Maurea N. Resveratrol in Cancer Patients: From Bench to Bedside. Int J Mol Sci. 2020;21(8):2945. https://doi.org/10.3390/ijms21082945.
  • Almatroodi SA, A Alsahli M, S M Aljohani A, Alhumaydhi FA, Babiker AY, Khan AA, Rahmani AH. Potential therapeutic targets of resveratrol, a plant polyphenol, and its role in the therapy of various types of cancer. Molecules. 2022;27(9):2665. https://doi.org/10.3390/molecules27092665.
  • Roshani M, Jafari A, Loghman A, Sheida AH, Taghavi T, Tamehri Zadeh SS, Hamblin MR, Homayounfal M, Mirzaei H. Applications of resveratrol in the treatment of gastrointestinal cancer. Biomed Pharmacother. 2022;153:113274. https://doi.org/10.1016/j.biopha.2022.113274.
  • Fu X, Li M, Tang C, Huang Z, Najafi M. Targeting of cancer cell death mechanisms by resveratrol: a review. Apoptosis. 2021;26(11-12):561-573. https://doi.org/10.1007/s10495-021-01689-7.
  • Woodall CE, Li Y, Liu QH, Wo J, Martin RC. Chemoprevention of metaplasia initiation and carcinogenic progression to esophageal adenocarcinoma by resveratrol supplementation. Anticancer Drugs. 2009;20(6):437-43. https://doi.org/10.1097/CAD.0b013e32832afb95.
  • Tang Q, Li G, Wei X, Zhang J, Chiu JF, Hasenmayer D, Zhang D, Zhang H. Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma. Cancer Lett. 2013;336(2):325-37. https://doi.org/10.1016/j.canlet.2013.03.023.
  • Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, Al-Mohannadi A, Abdel-Rahman WM, Eid AH, Nasrallah GK, Pintus G. Potential adverse effects of resveratrol: A literature review. Int J Mol Sci. 2020;21(6):2084. https://doi.org/10.3390/ijms21062084.
  • Galiniak S, Aebisher D, Bartusik-Aebisher D. Health benefits of resveratrol administration. Acta Biochim Pol. 2019;66(1):13-21. https://doi.org/10.18388/abp.2018_2749.
  • Yang R, Dong H, Jia S, Yang Z. Resveratrol as a modulatory of apoptosis and autophagy in cancer therapy. Clin Transl Oncol. 2022;24(7):1219-1230. https://doi.org/10.1007/s12094-021-02770-y.
  • Fan GH, Wang ZM, Yang X, Xu LP, Qin Q, Zhang C, Ma JX, Cheng HY, Sun XC. Resveratrol inhibits oesophageal adenocarcinoma cell proliferation via AMP-activated protein kinase signaling. Asian Pac J Cancer Prev. 2014;15(2):677-82. https://doi.org/10.7314/apjcp.2014.15.2.677.
  • Dhir H, Choudhury M, Patil K, Cheung C, Bodlak A, Pardo D, Adams A, Travaglino S, Rojas JA, Pai SB. Interception of signaling circuits of esophageal adenocarcinoma cells by resveratrol reveals molecular and immunomodulatory signatures. Cancers (Basel). 2021;13(22):5811. https://doi.org/10.3390/cancers13225811.
  • Lin YS, Hsieh CY, Kuo TT, Lin CC, Lin CY, Sher YP. Resveratrol-mediated ADAM9 degradation decreases cancer progression and provides synergistic effects in combination with chemotherapy. Am J Cancer Res. 2020;10(11):3828-3837.
  • Zhao Y, Tang H, Zeng X, Ye D, Liu J. Resveratrol inhibits proliferation, migration and invasion via Akt and ERK1/2 signaling pathways in renal cell carcinoma cells. Biomed Pharmacother. 2018;98:36-44. https://doi.org/10.1016/j.biopha.2017.12.029.
  • Gweon EJ, Kim SJ. Resveratrol induces MMP-9 and cell migration via the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells. Oncol Rep. 2013;29(2):826-34. https://doi.org/10.3892/or.2012.2151.
  • Singh CK, Ndiaye MA, Ahmad N. Resveratrol and cancer: Challenges for clinical translation. Biochim Biophys Acta. 2015;1852(6):1178-85. https://doi.org/10.1016/j.bbadis.2014.11.004.

The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma

Year 2025, Volume: 15 Issue: 3, 629 - 635, 30.09.2025

Saime Batırel , Bengü Çetinkaya , Ayşe Mine Yılmaz

https://doi.org/10.33808/clinexphealthsci.1646378

Abstract

Objective: Resveratrol is a small polyphenol that has been extensively researched across various therapeutic areas. Its inhibitory effect on esophageal cancer cell growth has also been demonstrated in a dose- and time-dependent manner. However, the underlying mechanism of this effect has not been fully elucidated yet. We aimed to investigate the anti-proliferative and anti-metastatic effects of resveratrol on esophageal adenocarcinoma (EAC) cells in vitro.
Methods: The EAC cells were treated with various doses of resveratrol, and cell viability was determined using the WST-1 assay. The apoptosis rate and the level of intracellular reactive oxygen species (ROS) were measured using flow cytometry. Adhesion, wound healing, and colony formation assays were carried out to evaluate the anti-metastatic effects of resveratrol.
Results: Resveratrol decreased the cell viability of OE33 cells in a dose-dependent manner. 150 µM resveratrol reduced cell viability by 49% compared to the control by increasing ROS levels. This inhibition was associated with the induction of apoptosis. The analysis revealed that resveratrol also suppressed the adhesion, migration, and colony forming capacity of the cells.
Conclusion: Resveratrol lower the viability and metastatic potential of EAC cells. These findings suggest resveratrol may be further evaluated clinically for this malignancy in humans.

Keywords

Resveratrol Esophageal adenocarcinoma anti-tumor anti-metastatic

References

  • Lander S, Lander E, Gibson MK. Esophageal cancer: Overview, risk factors, and reasons for the rise. Curr Gastroenterol Rep. 2023;25(11):275-279. https://doi.org/10.1007/s11894-023-00899-0.
  • Due SL, Watson DI, Hussey DJ. Oestrogen receptors: A potential therapeutic target in oesophageal adenocarcinoma? ANZ J Surg. 2021;91(7-8):1390-1396. https://doi.org/10.1111/ans.17054.
  • Jiang Z, Chen K, Cheng L, Yan B, Qian W, Cao J, Li J, Wu E, Ma Q, Yang W. Resveratrol and cancer treatment: updates. Ann N Y Acad Sci. 2017;1403(1):59-69. https://doi.org/10.1111/nyas.13466.
  • Petrick JL, Steck SE, Bradshaw PT, Trivers KF, Abrahamson PE, Engel LS, He K, Chow WH, Mayne ST, Risch HA, Vaughan TL, Gammon MD. Dietary intake of flavonoids and oesophageal and gastric cancer: Incidence and survival in the United States of America (USA). Br J Cancer. 2015;112(7):1291-300. https://doi.org/10.1038/bjc.2015.25.
  • Jin Z, Feng W, Ji Y, Jin L. Resveratrol mediates cell cycle arrest and cell death in human esophageal squamous cell carcinoma by directly targeting the EGFR signaling pathway. Oncol Lett. 2017;13(1):347-355. https://doi.org/10.3892/ol.2016.5391.
  • Baek SH, Ko JH, Lee H, Jung J, Kong M, Lee JW, Lee J, Chinnathambi A, Zayed ME, Alharbi SA, Lee SG, Shim BS, Sethi G, Kim SH, Yang WM, Um JY, Ahn KS. Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: Role in apoptosis induction and radiosensitization in head and neck tumor cells. Phytomedicine. 2016;23(5):566-77. https://doi.org/10.1016/j.phymed.2016.02.011.
  • Harikumar KB, Kunnumakkara AB, Sethi G, Diagaradjane P, Anand P, Pandey MK, Gelovani J, Krishnan S, Guha S, Aggarwal BB. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010;127(2):257-68. https://doi.org/10.1002/ijc.25041.
  • Lin Y, Yngve A, Lagergren J, Lu Y. A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer. Br J Nutr. 2014;112(12):2002-9. https://doi.org/10.1017/S0007114514003055.
  • Zhou HB, Yan Y, Sun YN, Zhu JR. Resveratrol induces apoptosis in human esophageal carcinoma cells. World J Gastroenterol. 2003;9(3):408-11. https://doi.org/10.3748/wjg.v9.i3.408.
  • Klingelhöfer D, Zhu Y, Braun M, Brüggmann D, Schöffel N, Groneberg DA. A world map of esophagus cancer research: a critical accounting. J Transl Med. 2019;17(1):150. https://doi.org/10.1186/s12967-019-1902-7.
  • Chung MY, Lim TG, Lee KW. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development. World J Gastroenterol. 2013;19(7):984-93. https://doi.org/10.3748/wjg.v19.i7.984.
  • Cione E, La Torre C, Cannataro R, Caroleo MC, Plastina P, Gallelli L. Quercetin, epigallocatechin gallate, curcumin, and resveratrol: From dietary sources to human microrna modulation. Molecules. 2019;25(1):63. https://doi.org/10.3390/molecules25010063.
  • Berretta M, Bignucolo A, Di Francia R, Comello F, Facchini G, Ceccarelli M, Iaffaioli RV, Quagliariello V, Maurea N. Resveratrol in Cancer Patients: From Bench to Bedside. Int J Mol Sci. 2020;21(8):2945. https://doi.org/10.3390/ijms21082945.
  • Almatroodi SA, A Alsahli M, S M Aljohani A, Alhumaydhi FA, Babiker AY, Khan AA, Rahmani AH. Potential therapeutic targets of resveratrol, a plant polyphenol, and its role in the therapy of various types of cancer. Molecules. 2022;27(9):2665. https://doi.org/10.3390/molecules27092665.
  • Roshani M, Jafari A, Loghman A, Sheida AH, Taghavi T, Tamehri Zadeh SS, Hamblin MR, Homayounfal M, Mirzaei H. Applications of resveratrol in the treatment of gastrointestinal cancer. Biomed Pharmacother. 2022;153:113274. https://doi.org/10.1016/j.biopha.2022.113274.
  • Fu X, Li M, Tang C, Huang Z, Najafi M. Targeting of cancer cell death mechanisms by resveratrol: a review. Apoptosis. 2021;26(11-12):561-573. https://doi.org/10.1007/s10495-021-01689-7.
  • Woodall CE, Li Y, Liu QH, Wo J, Martin RC. Chemoprevention of metaplasia initiation and carcinogenic progression to esophageal adenocarcinoma by resveratrol supplementation. Anticancer Drugs. 2009;20(6):437-43. https://doi.org/10.1097/CAD.0b013e32832afb95.
  • Tang Q, Li G, Wei X, Zhang J, Chiu JF, Hasenmayer D, Zhang D, Zhang H. Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma. Cancer Lett. 2013;336(2):325-37. https://doi.org/10.1016/j.canlet.2013.03.023.
  • Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, Al-Mohannadi A, Abdel-Rahman WM, Eid AH, Nasrallah GK, Pintus G. Potential adverse effects of resveratrol: A literature review. Int J Mol Sci. 2020;21(6):2084. https://doi.org/10.3390/ijms21062084.
  • Galiniak S, Aebisher D, Bartusik-Aebisher D. Health benefits of resveratrol administration. Acta Biochim Pol. 2019;66(1):13-21. https://doi.org/10.18388/abp.2018_2749.
  • Yang R, Dong H, Jia S, Yang Z. Resveratrol as a modulatory of apoptosis and autophagy in cancer therapy. Clin Transl Oncol. 2022;24(7):1219-1230. https://doi.org/10.1007/s12094-021-02770-y.
  • Fan GH, Wang ZM, Yang X, Xu LP, Qin Q, Zhang C, Ma JX, Cheng HY, Sun XC. Resveratrol inhibits oesophageal adenocarcinoma cell proliferation via AMP-activated protein kinase signaling. Asian Pac J Cancer Prev. 2014;15(2):677-82. https://doi.org/10.7314/apjcp.2014.15.2.677.
  • Dhir H, Choudhury M, Patil K, Cheung C, Bodlak A, Pardo D, Adams A, Travaglino S, Rojas JA, Pai SB. Interception of signaling circuits of esophageal adenocarcinoma cells by resveratrol reveals molecular and immunomodulatory signatures. Cancers (Basel). 2021;13(22):5811. https://doi.org/10.3390/cancers13225811.
  • Lin YS, Hsieh CY, Kuo TT, Lin CC, Lin CY, Sher YP. Resveratrol-mediated ADAM9 degradation decreases cancer progression and provides synergistic effects in combination with chemotherapy. Am J Cancer Res. 2020;10(11):3828-3837.
  • Zhao Y, Tang H, Zeng X, Ye D, Liu J. Resveratrol inhibits proliferation, migration and invasion via Akt and ERK1/2 signaling pathways in renal cell carcinoma cells. Biomed Pharmacother. 2018;98:36-44. https://doi.org/10.1016/j.biopha.2017.12.029.
  • Gweon EJ, Kim SJ. Resveratrol induces MMP-9 and cell migration via the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells. Oncol Rep. 2013;29(2):826-34. https://doi.org/10.3892/or.2012.2151.
  • Singh CK, Ndiaye MA, Ahmad N. Resveratrol and cancer: Challenges for clinical translation. Biochim Biophys Acta. 2015;1852(6):1178-85. https://doi.org/10.1016/j.bbadis.2014.11.004.
There are 27 citations in total.

Details

Primary Language English
Subjects Cancer Cell Biology
Journal Section Articles
Authors

Saime Batırel 0000-0002-8993-6029

Bengü Çetinkaya 0000-0003-3487-7065

Ayşe Mine Yılmaz 0000-0003-0802-523X

Early Pub Date September 30, 2025
Publication Date September 30, 2025
Submission Date February 25, 2025
Acceptance Date August 1, 2025
Published in Issue Year 2025 Volume: 15 Issue: 3

Cite

APA Batırel, S., Çetinkaya, B., & Yılmaz, A. M. (2025). The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma. Clinical and Experimental Health Sciences, 15(3), 629-635. https://doi.org/10.33808/clinexphealthsci.1646378
AMA Batırel S, Çetinkaya B, Yılmaz AM. The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma. Clinical and Experimental Health Sciences. September 2025;15(3):629-635. doi:10.33808/clinexphealthsci.1646378
Chicago Batırel, Saime, Bengü Çetinkaya, and Ayşe Mine Yılmaz. “The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma”. Clinical and Experimental Health Sciences 15, no. 3 (September 2025): 629-35. https://doi.org/10.33808/clinexphealthsci.1646378.
EndNote Batırel S, Çetinkaya B, Yılmaz AM (September 1, 2025) The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma. Clinical and Experimental Health Sciences 15 3 629–635.
IEEE S. Batırel, B. Çetinkaya, and A. M. Yılmaz, “The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma”, Clinical and Experimental Health Sciences, vol. 15, no. 3, pp. 629–635, 2025, doi: 10.33808/clinexphealthsci.1646378.
ISNAD Batırel, Saime et al. “The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma”. Clinical and Experimental Health Sciences 15/3 (September2025), 629-635. https://doi.org/10.33808/clinexphealthsci.1646378.
JAMA Batırel S, Çetinkaya B, Yılmaz AM. The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma. Clinical and Experimental Health Sciences. 2025;15:629–635.
MLA Batırel, Saime et al. “The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma”. Clinical and Experimental Health Sciences, vol. 15, no. 3, 2025, pp. 629-35, doi:10.33808/clinexphealthsci.1646378.
Vancouver Batırel S, Çetinkaya B, Yılmaz AM. The Inhibitory Effects of Resveratrol on Tumor Growth and Metastasis in Esophageal Adenocarcinoma. Clinical and Experimental Health Sciences. 2025;15(3):629-35.
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