Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62
Yıl: 2022 Cilt: 47 Sayı: 4 Sayfa Aralığı: 1620 - 1629 Metin Dili: İngilizce DOI: 10.17826/cumj.1182496 İndeks Tarihi: 09-01-2023
Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62
Öz: Purpose: The aim of this study was to investigate the role of Ganoderma lucidum (GL) in cell proliferation and autophagy in breast cancer cell lines. Materials and Methods: Cell lines were cultured in vitro and the appropriate dose was determined by the MTT method. In order to show the effect of GL on autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines, Beclin-1, LC3 and p62 expression were examined by immunohistochemistry staining. Additionally, cell cycle analysis was carried out in GL-treated and untreated cells using a cell cycle analysis kit to look into how GL affects cell division. Results: Viability level was significantly reduced in MCF-7 and MDA-MB-231 cells incubated with 40 and 80 μM concentrations of GL for 24 hours. In addition, GL induced the initiation of autophagy in MDA-MB-231 and MCF-7 cells, as evidenced by enhanced levels of Beclin-1, LC3 and p62 expression. At the same time, this study showed that GL induced cell cycle arrest in the G2/M phases. Conclusion: GL has anti-proliferative activity by arresting the cell cycle at the G2/M phase and accelerates cell death by inducing autophagy, particularly in aggressive breast cancers that are resistant to treatment..
Anahtar Kelime: Ganoderma lucidum farklı hormonal duyarlılığa sahip meme kanseri hücre hatlarında Beclin-1/LC3 ve p62'yi düzenleyerek proliferasyonu inhibe eder ve otofajiyi teşvik eder
Öz: Amaç: Bu çalışmada meme kanseri hücre dizilerinde Ganoderma lucidumun (GL) hücre proliferasyonu ve otofaji ile ilişkisinin belirlenmesi amaçlanmıştır. Gereç ve Yöntem: Hücre hatları in vitro ortamda kültüre edildi ve uygun doz MTT yöntemi ile belirlendi. MCF-7 ve MDA-MB-231 meme kanseri hücre hatlarında GL'nin otofaji üzerindeki etkisini göstermek için, immünohistokimya boyaması ile Beclin-1, LC3 ve p62 ekspresyonu incelenmiştir. Ek olarak, GL'nin hücre bölünmesi üzerindeki etkisini araştırmak için, bir hücre döngüsü analiz kiti kullanılarak GL uygulanan ve uygulanmayan hücre döngüsü analizi yapıldı. Bulgular: 24 saat süreyle GL'nin 40 ve 80 μM’lik konsantrasyonlarıyla inkübe edilen MCF-7 ve MDA-MB-231 hücrelerinde canlılık düzeyinin önemli ölçüde azaldığı gösterildi. Ek olarak, GL, artan Beclin-1, LC3 ve p62 ekspresyonu seviyeleri ile kanıtlandığı gibi, MCF-7 ve MDA-MB-231 hücrelerinde otofajinin başlatılmasını indüklemiştir. Aynı zamanda, bu çalışma GL'nin G2/M fazlarında hücre döngüsü durmasını indüklediğini gösterdi. Sonuç: GL, hücre döngüsünü G2/M fazında durdurarak anti-proliferatif aktiviteye sahiptir ve özellikle tedaviye dirençli agresif meme kanserlerinde otofajiyi indükleyerek hücre ölümünü hızlandırır.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Farghadani R, Naidu R. Curcumin: Modulator of key molecular signaling pathways in hormone- independent breast cancer. Cancers. 2021;13:3427.
- 2. Ensenyat-Mendez M, Llinàs-Arias P, Orozco JIJ, Íñiguez-Muñoz S, Salomon MP, Sesé B et al. Current triple-negative breast cancer subtypes: Dissecting the most aggressive form of breast cancer. Front Oncol. 2021;11:681476.
- 3. Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009;9:631-43.
- 4. Liu CY, Wu CY, Petrossian K, Huang TT, Tseng LM, Chen S. Treatment for the endocrine resistant breast cancer: current options and future perspectives. J Steroid Biochem Mol Biol. 2017;172:166-75.
- 5. Nofech-Mozes S, Trudeau M, Kahn HK, Dent R, Rawlinson E, Sun P et al. Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers. Breast Cancer Res Treat. 2009;118:131-7.
- 6. Yao H, He G, Yan S, Chen C, Song L, Rosol TJ et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget. 2017; 8:1913-24.
- 7. Pan H, Wang Y, Na K, Wang Y, Wang L, Li Z et al. Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation. Cell Death Dis. 2019;10:456.
- 8. Zhong L, Yan P, Lam WC, Yao L, Bian Z. Coriolus versicolor and ganoderma lucidum related natural products as an adjunct therapy for cancers: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol. 2019;10:703.
- 9. Gurovic MSV, Viceconte FR, Pereyra MT. DNA damaging potential of Ganoderma lucidum extract. J Ethnopharmacol. 2018;217:83-88.
- 10. Edinger AL, Thompson CB. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004;16:663-9.
- 11. Andrade-Tomaz M, de Souza I, Rocha CRR, Gomes LR. The role of chaperone-mediated autophagy in cell cycle control and its implications in cancer. Cells 2020;9:2140.
- 12. Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17:93- 115.
- 13. Liu X, Xu Y, Li Y, Pan Y, Sun Z, Zhao S et al. Ganoderma lucidum fruiting body extracts inhibit colorectal cancer by inducing apoptosis, autophagy, and G0/G1 phase cell cycle arrest in vitro and in vivo. Am J Transl Res. 2020;12:2675-84.
- 14. Kawabata T, Yoshimori T. Autophagosome biogenesis and human health. Cell Discov. 2020;6:33.
- 15. Kawabata T, Yoshimori T. Beyond starvation: an update on the autophagic machinery and its functions. J Mol Cell Cardiol. 2016;95:2-10.
- 16. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008;132:27-42.
- 17. Aman Y, Schmauck-Medina T, Hansen M, Morimoto Rl, Simon AK, Bjedov I et al. Autophagy in healthy aging and disease. Nat Aging. 2021;1:634-50.
- 18. Pan P, Huang Y, Oshima K, Yearsley M, Zhang J, Arnold M et al. The immunomodulatory potential of natural compounds in tumor-bearing mice and humans. Crit Rev Food Sci Nutr. 2019;59:992-1007.
- 19. Suarez-Arroyo IJ, Rosario-Acevedo R, Aguilar-Perez A, Clemente PL, Cubano LA, Serrano J et al. Anti- tumor effects of ganoderma lucidum (Reishi) in inflammatory breast cancer in in vivo and in vitro models. PlosOne. 2013;8:e57431.
- 20. Hamurcu Z, Delibaşı N, Nalbantoğlu U, Şener EF, Nurdinov N, Taşcı B et al. FOXM1 plays a role in autoghagy by transcriptionally regulating Beclin-1 and LC-3 genes in human triple-negative breast cancer cells. J Mol Med. 2019;97:491-508.
- 21. Bahuguna A, Khan I, Bajpai VK, Kang SC. MTT assay to evaluate the cytotoxic potential of a drug. Bangladesh J Pharmacol. 2017;12:115-18.
- 22. Yay A, Göktepe Ö, Bahadır A, Özdamar S, Öktem İS, Çoruh A et al. Assessment of markers expressed in human hair follicles according to different skin regions. Adv Clin Exp Med. 2018;27:929-39.
- 23. Salkın H, Gönen ZB, Ergen E, Bahar D, Çetin M. Effects of TGF-β1 Overexpression on biological characteristics of human dental pulp-derived mesenchymal stromal cells. Int J Stem Cells. 2019;12:170-82.
- 24. Parekh HS, Liu G, Wei MQ. A new dawn for the use of traditional Chinese medicine in cancer therapy. Mol. Cancer. 2009;8:21.
- 25. Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov. 2021;20:200-16.
- 26. Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6:201.
- 27. Kladar NV, Gavaric NS, Bozin BN. Ganoderma: insights into anticancer effects. Eur. J Cancer Prev. 2016;25:462-71.
- 28. Li WJ, Chen Y, Nie SP, Xie MY, He M, Zhang SS et al. Ganoderma atrum polysaccharide induces anti- tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response. J Cell Biochem. 2011;112:860-71.
- 29. Sun Z, Huang K, Fu X, Zhou Z, Cui Y, Li H. A chemically sulfated polysaccharide derived from Ganoderma luciduminduces mitochondrial-mediated apoptosis in human osteo-sarcoma MG63 cells. Tumour Biol. 2014;35:9919-26.
- 30. Li WD, Zhang BD, Wei R, Liu JH, Lin ZB. Reversal effect of Ganoderma lucidum polysaccharide on multidrug resistance in K562/ADM cell line. Acta Pharmacol Sin. 2008;29:620-27.
- 31. Fuchs Y, Steller H. Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol. 2015;16:329- 44.
- 32. Jiang GM, Tan Y, Wang H, Peng L, Chen HT, Meng XJ et al. The relationship between autophagy and the immune system and its applications for tumor immunotherapy. Mol Cancer. 2019;18:17.
- 33. Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 2005;5:231-37.
- 34. Okada H, Mak TW. Pathways of apoptotic and non- apoptotic death in tumour cells. Nat Rev Cancer. 2004;4:592-603.
- 35. Zhao Y, Yuan B, Onda K, Sugiyama K, Tanaka S, Takagi N et al. Anticancer efficacies of arsenic disulfide through apoptosis induction, cell cycle arrest, and pro-survival signal inhibition in human breast cancer cells. Am J Cancer Res. 2018;8:366-86.
- 36. Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2022;23:74– 88.
- 37. Hu H, Ahn NS, Yang X, Lee YS, Kang KS. Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int J Cancer. 2002;102:250-53.
- 38. Wu G, Qian Z, Guo J, Hu D, Bao J, Xie J et al. Ganoderma lucidum extract induces G1 cell cycle arrest, and apoptosis in human breast cancer cells. Am J Chin Med. 2012;40:631-42.
| APA | Göktepe Ö, Önder G, Bolat D, ÇINAR V, Hamurcu Z, yakan b, Yay A (2022). Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. , 1620 - 1629. 10.17826/cumj.1182496 |
| Chicago | Göktepe Özge,Önder Gözde Özge,Bolat Demet,ÇINAR Venhar,Hamurcu Zuhal,yakan birkan,Yay Arzu Hanım Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. (2022): 1620 - 1629. 10.17826/cumj.1182496 |
| MLA | Göktepe Özge,Önder Gözde Özge,Bolat Demet,ÇINAR Venhar,Hamurcu Zuhal,yakan birkan,Yay Arzu Hanım Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. , 2022, ss.1620 - 1629. 10.17826/cumj.1182496 |
| AMA | Göktepe Ö,Önder G,Bolat D,ÇINAR V,Hamurcu Z,yakan b,Yay A Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. . 2022; 1620 - 1629. 10.17826/cumj.1182496 |
| Vancouver | Göktepe Ö,Önder G,Bolat D,ÇINAR V,Hamurcu Z,yakan b,Yay A Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. . 2022; 1620 - 1629. 10.17826/cumj.1182496 |
| IEEE | Göktepe Ö,Önder G,Bolat D,ÇINAR V,Hamurcu Z,yakan b,Yay A "Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62." , ss.1620 - 1629, 2022. 10.17826/cumj.1182496 |
| ISNAD | Göktepe, Özge vd. "Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62". (2022), 1620-1629. https://doi.org/10.17826/cumj.1182496 |
| APA | Göktepe Ö, Önder G, Bolat D, ÇINAR V, Hamurcu Z, yakan b, Yay A (2022). Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. Cukurova Medical Journal, 47(4), 1620 - 1629. 10.17826/cumj.1182496 |
| Chicago | Göktepe Özge,Önder Gözde Özge,Bolat Demet,ÇINAR Venhar,Hamurcu Zuhal,yakan birkan,Yay Arzu Hanım Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. Cukurova Medical Journal 47, no.4 (2022): 1620 - 1629. 10.17826/cumj.1182496 |
| MLA | Göktepe Özge,Önder Gözde Özge,Bolat Demet,ÇINAR Venhar,Hamurcu Zuhal,yakan birkan,Yay Arzu Hanım Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. Cukurova Medical Journal, vol.47, no.4, 2022, ss.1620 - 1629. 10.17826/cumj.1182496 |
| AMA | Göktepe Ö,Önder G,Bolat D,ÇINAR V,Hamurcu Z,yakan b,Yay A Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. Cukurova Medical Journal. 2022; 47(4): 1620 - 1629. 10.17826/cumj.1182496 |
| Vancouver | Göktepe Ö,Önder G,Bolat D,ÇINAR V,Hamurcu Z,yakan b,Yay A Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62. Cukurova Medical Journal. 2022; 47(4): 1620 - 1629. 10.17826/cumj.1182496 |
| IEEE | Göktepe Ö,Önder G,Bolat D,ÇINAR V,Hamurcu Z,yakan b,Yay A "Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62." Cukurova Medical Journal, 47, ss.1620 - 1629, 2022. 10.17826/cumj.1182496 |
| ISNAD | Göktepe, Özge vd. "Ganoderma lucidum inhibits proliferation and promotes autophagy in breast cancer cell lines with varying hormonal sensitivity by regulating Beclin-1, LC3, and p62". Cukurova Medical Journal 47/4 (2022), 1620-1629. https://doi.org/10.17826/cumj.1182496 |
