The Effects of Resveratrol Treatment on Bcl-2 and Bax Gene Expression in Endometriotic Compared with Non-Endometriotic Stromal Cells
Background: We aimed to examine resveratrol effects on gene expression of Bcl-2, Bax and Bcl-2/Bax ratio in endometrial stromal cells derived from women with and without endometriosis.
Methods: Endometrial tissues were obtained from 40 endometriotic patients and 15 non-endometriotic controls undergoing laparoscopic surgery or hysterectomy in the gynecology ward of Rassoul Akram Hospital, Tehran, Iran from 2015 to 2017. After the enzymatic digestion, eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells from patients with endometriosis as well as endometrial stromal cells from non-endometriotic controls (CESCs) were treated with or without resveratrol (100 µM) and the levels of Bcl-2, Bax and Bcl-2/Bax gene expression ratio in the cells from all origins were examined at 6, 24 and 48 h post-treatment by real-time PCR.
Results: Resveratrol treatment increased Bcl-2 expression in CESCs at 24 and 48 h and in EuESCs at 48 h (P<0.05), but had no significant effects on the expression of this gene in EESCs. On the other hand, resveratrol treatment increased Bax expression in EuESCs at 6 h and decreased its expression in EESCs at 48 h (P<0.05). Regarding the Bcl-2/Bax gene expression ratio, resveratrol treatment increased Bcl-2/Bax gene expression ratio in CESCs and EuESCs at 48 h (P<0.01). However, this treatment had no significant differential effect on Bcl-2 and Bcl-2/Bax gene expression ratio between CESCs and EuESCs at 48 h.
Conclusion: Resveratrol treatment significantly increased Bcl-2/Bax gene expression ratio in EuESCs and CESCs but had no significant effect in EESCs.
2. Nisolle M, Donnez J (1997). Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril, 68 (4): 585-96.
3. Gebel HM, Braun DP, Tambur A et al (1998). Spontaneous apoptosis of endometrial tissue is impaired in women with endometriosis. Fertil Steril, 69 (6): 1042-7.
4. Wingfield M, Macpherson A, Healy DL et al (1995). Cell proliferation is increased in the endometrium of women with endo-metriosis. Fertil Steril, 64 (2): 340-6.
5. Dmowski W, Ding J, Shen J et al (2001). Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis. Hum Reprod, 16 (9): 1802-8.
6. Nasu K, Nishida M, Kawano Y et al (2011). Aberrant expression of apoptosis-related molecules in endometriosis: a possible mechanism underlying the pathogenesis of endometriosis. Reprod Sci, 18 (3): 206-18.
7. Mohammadi RK, Arablou T (2017). Resveratrol and endometriosis: In vitro and animal studies and underlying mechanisms. Biomed Pharmacother, 91: 220-8.
8. Guerrero RF, Garcia-Parrilla MC, Puertas B et al (2009). Wine, resveratrol and health: a review. Nat Prod Commun, 4 (5): 635-58.
9. Baur JA, Sinclair DA (2006). Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov, 5 (6): 493-506.
10. Bruner-Tran KL, Osteen KG, Taylor HS et al (2011). Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro. Biol Reprod, 84 (1): 106-12.
11. Ricci AG, Olivares CN, Bilotas MA et al (2013). Natural therapies assessment for the treatment of endometriosis. Hum Reprod, 28 (1): 178-88.
12. Bayoglu Tekin Y, Guven S, Kirbas A et al (2015). Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis? Eur J Obstet Gynecol Reprod Biol,184:1-6.
13. Taguchi A, Wada-Hiraike O, Kawana K et al (2014). Resveratrol suppresses inflammatory responses in endometrial stromal cells derived from endometriosis: a possible role of the sirtuin 1 pathway. J Obstet Gynaecol Res, 40 (3): 770-8.
14. Ergenoglu AM, Yeniel AO, Erbas O et al (2013). Regression of endometrial implants by resveratrol in an experimentally induced endometriosis model in rats. Reprod Sci, 20 (10): 1230-6.
15. Ozcan Cenksoy P, Oktem M, Erdem O et al (2015). A potential novel treatment strategy: inhibition of angiogenesis and inflammation by resveratrol for regression of endometriosis in an experimental rat model. Gynecol Endocrinol, 31 (3): 219-24.
16. Yavuz S, Aydin NE, Celik O et al (2014). Resveratrol successfully treats experimental endometriosis through modulation of oxidative stress and lipid peroxidation. J Cancer Res Ther, 10 (2): 324-9.
17. Rudzitis-Auth J, Menger MD, Laschke MW (2013). Resveratrol is a potent inhibitor of vascularization and cell proliferation in experimental endometriosis. Hum Reprod, 28 (5): 1339-47.
18. Taguchi A, Koga K, Kawana K et al (2016). Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells. Am J Reprod Immunol, 75 (4): 486-92.
19. Canis M, Donnez JG, Guzick DS et al (1997). Revised American society for reproductive medicine classification of endometriosis: 1996. Fertil Steril, 67 (5): 817-21.
20. Delbandi AA, Mahmoudi M, Shervin A et al (2013). Eutopic and ectopic stromal cells from patients with endometriosis exhibit differential invasive, adhesive, and proliferative behavior. Fertil Steril, 100 (3): 761-9.
21. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65 (1-2): 55-63.
22. Islam S, Hassan F, Mu MM et al (2004). Piceatannol prevents lipopolysaccharide (LPS)‐induced nitric oxide (NO) production and nuclear factor (NF)‐κB activation by inhibiting IκB kinase (IKK). Microbiol Immunol, 48(10): 729-36.
23. Rashidi N, Mirahmadian M, Jeddi-Tehrani M et al (2015). Lipopolysaccharide-and lipoteichoic acid-mediated pro-inflammatory cytokine production and modulation of TLR2, TLR4 and MyD88 expression in human endometrial cells. J Reprod Infertil, 16 (2): 72-81.
24. Wang H, Xu YS, Wang ML et al (2017). Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: Implications for the treatment of neurodegenerative disorders. Int J Mol Med, 39 (4): 819-830.
25. Scott E, Steward WP, Gescher AJ et al (2012). Resveratrol in human cancer chemoprevention–choosing the ‘right’dose. Mol Nutr Food Res, 56 (1): 7-13.
26. Delbandi AA, Mahmoudi M, Shervin A et al (2016). 1, 25‐Dihydroxy Vitamin D3 Modulates Endometriosis‐Related Features of Human Endometriotic Stromal Cells. Am J Reprod Immunol, 75 (4): 461-73.
27. Liang CZ, Zhang JK, Shi Z et al (2012). Matrine induces caspase-dependent apoptosis in human osteosarcoma cells in vitro and in vivo through the upregulation of Bax and Fas/FasL and downregulation of Bcl-2. Cancer Chemother Pharmacol, 69 (2): 317-31.
28. Gao C, Zhang Z, Liu W et al (2010). Reduced microRNA‐218 expression is associated with high nuclear factor kappa B activation in gastric cancer. Cancer, 116 (1): 41-9.
29. Sharpe‐Timms KL (2001). Endometrial anomalies in women with endometriosis. Ann N Y Acad Sci, 943 (1): 131-47.
30. Harada T, Taniguchi F, Izawa M et al (2007). Apoptosis and endometriosis. Front Biosci, 12: 3140-51.
31. Szczepańska M, Koźlik J, Skrzypczak J et al (2003). Oxidative stress may be a piece in the endometriosis puzzle. Fertil Steril, 79 (6): 1288-93.
32. Donnez J, Van Langendonckt A, Casanas-Roux F et al (2002). Current thinking on the pathogenesis of endometriosis. Gynecol Obstet Invest, 1: 52-8.
33. Matés JM, Sánchez-Jiménez FM (2000). Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol, 32 (2): 157-70.
34. Kong Q, Beel J, Lillehei K (2000). A threshold concept for cancer therapy. Med Hypotheses, 55 (1): 29-35.
35. O'brien N, Woods J, Aherne S et al (2000). Cytotoxicity, genotoxicity and oxidative reactions in cell-culture models: modulatory effects of phytochemicals. Biochem Soc Trans, 28 (2): 22-6.
36. Salganik RI, Albright CD, Rodgers J et al (2000). Dietary antioxidant depletion: enhancement of tumor apoptosis and inhibition of brain tumor growth in transgenic mice. Carcinogenesis, 21 (5): 909-14.
37. Bagchi D, Garg A, Krohn R et al (1997). Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol, 95 (2): 179-89.
38. Jang J-H, Surh Y-J (2001). Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutat Res, 496 (1): 181-90.
39. Nicolini G, Rigolio R, Miloso M et al (2001). Anti-apoptotic effect of trans-resveratrol on paclitaxel-induced apoptosis in the human neuroblastoma SH-SY5Y cell line. Neurosci Lett, 302 (1): 41-4.
40. Hammond MG, Oh S-T, Anners J et al (1993). The effect of growth factors on the proliferation of human endometrial stromal cells in culture. Am J Obstet Gynecol, 168 (4): 1131-6.
41. Lin HY, Tang HY, Davis FB et al (2011). Resveratrol and Apoptosis. Ann N Y Acad Sci, 1215 (1): 79-88.