Gossypin’in prostat kanser hücrelerinde MMP-2 ve MMP-9 genleri üzerindeki etkisinin araştırılması

Yıl 2022, Cilt: 47 Sayı: 3, 1290 - 1295, 30.09.2022

Ebubekir Dirican , İrfan Çınar

https://doi.org/10.17826/cumj.1137306

Cited By: 1

Öz

Amaç: Bu çalışmada gossypin’in prostat kanser hücrelerinde matriks metalloproteinaz 2 (MMP-2) ve MMP-9 genlerinin mRNA ekspresyonu üzerindeki etkilerini araştırmak amaçlanmıştır.
Gereç ve Yöntem: PC3 hücreleri, kültür koşulları altında büyütüldü ve üç farklı konsantrasyonda (25-50-100 µg/ml) gossypin ve pozitif kontrol olarak sisplatin (50 µM) ile muamele edildi. Önce RNA izolasyonu gerçekleştirildi. Daha sonra cDNA sentezi gerçekleştirildi ve RT-PCR MMP-2 ve MMP-9 genlerinin mRNA ekspresyon seviyesini değerlendirmek için kullanıldı.
Bulgular: Gossypin, prostat kanser hücrelerinde MMP-2 ve MMP-9 mRNA ekspresyonunu konsantrasyona bağlı olarak azaltmıştır. PC3 hücrelerinde gossypin’in üç konsantrasyonu (25 -50-100 µg/ml) MMP-2 genin mRNA ekspresyonunu azaltmıştır. MMP-2 geni ekspresyonu kat değişim (fold change) değeri 100 µg/ml gossypin uygulanan grupta 0.3482 ± 0.040 iken, kontrol grubunda ise 1.007 ± 0.1425 olarak belirlenmiştir. Ayrıca 50 µg/ml ve 100 µg/ml gossypin dozları, MMP-9 genin mRNA ekspresyonunu azaltmıştır. MMP-9 geni ekspresyon seviyesi ise prostat kanser hücrelerinde 100 µg/ml gossypin uygulanan grupta 0.4740 ± 0.038 iken, kontrol grubunda ise 1.009 ± 0.1687 olarak belirlenmiştir. MMP-2 ve MMP-9 genlerinin ekspresyonları arasında pozitif bir korelasyon olduğu gösterildi.
Sonuç: Elde edilen sonuçlara göre, gossypin’in prostat kanser hücrelerinde MMP-2 ve MMP-9 genlerinin ekspresyonunu azalttığı ve gossypin’in anti-kanser etkisinin ortaya çıkarılabilmesi için kanserde diğer genetik ve epigenetik mekanizmalar üzerindeki etkilerinin de araştırılmasına ihtiyaç olduğu görülmektedir.

Anahtar Kelimeler

Gossypin, MMP-2, MMP-9, PC-3, RT-PCR

Investigation of the effect of gossypin on MMP-2 and MMP-9 genes in prostate cancer cells

Öz

Purpose: The aim of this study is to explore the effects of gossypin on matrix metalloproteinases -2 (MMP-2) and MMP-9 genes in prostate cancer cells.
Materials and Methods: PC3 cells were grown in culture and treated with three different concentrations of gossypin (25-50-100 µg/ml) and cisplatin (50 µM) as a positive control. First, RNA isolation was performed. Then, cDNA synthesis was performed and RT-PCR was used to evaluate mRNA expression levels of MMP-2 and MMP-9 genes.
Results: Gossypin decreased MMP-2 and MMP-9 mRNA expression in prostate cancer cells in a concentration-dependent manner. Three concentrations (25-50-100 µg/ml) of gossypin in PC3 cells reduced the mRNA expression of the MMP-2 gene. While the fold change value of MMP-2 gene expression was 0.3482 ± 0.040 in the 100 µg/ml gossypin group, it was 1.007 ± 0.1425 in the control group. In addition, 50 µg/ml and 100 µg/ml concentrations of gossypin decreased the mRNA expression of the MMP-9 gene. The expression level of the MMP-9 gene in prostate cancer cells was 0.4740 ± 0.038 in the 100 µg/ml gossypin administered group, while it was 1.009 ± 0.1687 in the control group. There was a positive correlation between the expressions of the MMP-2 and MMP-9 genes.
Conclusion: According to the results obtained, it is seen that gossypin reduces the expression of MMP-2 and MMP-9 genes in prostate cancer cells and the effects of gossypin on other genetic and epigenetic mechanisms in cancer need to be investigated to reveal the anti-cancer.

Anahtar Kelimeler

Gossypin, MMP-2, MMP-9, PC-3, RT-PCR

Kaynakça

• 1. Wang S, Wei W, Ma N, Qu Y, Liu Q. Molecular mechanisms of ferroptosis and its role in prostate cancer therapy. Crit Rev Oncol Hematol. 2022:103732.
• 2. Jiang J, Tang X, Pu Y, Yang Y, Yang C, Tian Y et al. The Value of multimodality PET/CT ımaging in detecting prostate cancer biochemical recurrence. Front Endocrinol (Lausanne). 2022;13:897513.
• 3. Luchian I, Goriuc A, Sandu D, Covasa M. The role of matrix metalloproteinases (MMP-8, MMP-9, MMP-13) in periodontal and peri-ımplant pathological processes. Int J Mol Sci. 2022;23:1806.
• 4. Gonzalez-Avila G, Sommer B, Mendoza-Posada DA, Ramos C, Garcia-Hernandez AA, Falfan-Valencia R. Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit Rev Oncol Hematol. 2019;137:57-83.
• 5. Checchi V, Maravic T, Bellini P, Generali L, Consolo U, Breschi L et al. The Role of Matrix Metalloproteinases in Periodontal Disease. Int J Environ Res Public Health. 2020;17:4923.
• 6. Gonzalez-Avila G, Sommer B, Mendoza-Posada DA, Ramos C, Garcia-Hernandez AA, Falfan-Valencia R. Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit Rev Oncol Hematol. 2019;137:57-83.
• 7. Wang L, Wang X, Chen H, Zu X, Ma F, Liu K et al. Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2. Phyther Res. 2019;33:640-50.
• 8. Çınar İ, Yayla M, Binnetoğlu D. Gossypinin insan hepatom (Hep-3B) hücreleri üzerinde anti-proliferatif etkisi. Cukurova Med J. 2020;45:1165-72.
• 9. Babu BH, Jayram HN, Nair MG, Ajaikumar KB, Padikkala J. Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. J Exp Clin Cancer Res. 2003;22:581-89.
• 10. Kunnumakkara AB, Nair AS, Ahn KS, Pandet MK, Yi Z, Liu M et al. Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-κB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis. Blood. 2007;109:5112-21.
• 11. Cinar I. Apoptosis-ınducing activity and antiproliferative effect of gossypin on PC-3 prostate cancer cells. Anticancer Agents Med Chem. 2021;21:445-50.
• 12. Yang HK, Jeong KC, Kim YK, Jung ST. Role of matrix metalloproteinase (MMP) 2 and MMP-9 in soft tissue sarcoma. Clin Orthop Surg. 2014;6:443.
• 13. Lai CS, Li S, Miyauchi Y, Suzawa M, Ho CT, Pan MH. Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors. Food Funct. 2013;4:944.
• 14. Genís L, Gálvez BG, Gonzalo P, Arroyo AG. MT1-MMP: Universal or particular player in angiogenesis? Cancer Metastasis Rev. 2006;25:77-86.
• 15. Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res. 1998;58:1048-51.
• 16. Itoh Y, Nagase H. Matrix metalloproteinases in cancer. Essays Biochem. 2002;38:21-36.
• 17. Peng CC, Peng CH, Chen KC, Hsieh CL, Peng RY. The aqueous soluble polyphenolic fraction of psidium guajava leaves exhibits potent anti-angiogenesis and anti-migration actions on DU145 cells. Evidence-Based Complement Altern Med. 2011;2011:1–8.
• 18. Sauer C, Kappeler A, Spath M, Kaden JJ, Michel MS, Mayer D et al. Expression and activity of matrix metalloproteinases-2 and -9 in serum, core needle biopsies and tissue specimens of prostate cancer patients. Virchows Arch. 2004;444:518-26.
• 19. Yang MH, Jung SH, Um JY, Kumar AP, Sethi G, Ahn KS. Daidzin targets epithelial-to-mesenchymal transition process by attenuating manganese superoxide dismutase expression and PI3K/Akt/mTOR activation in tumor cells. Life Sci. 2022;295:120395.
• 20. Cai F, Zhang Y, Li J, Huang S, Gao R. Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway. Biosci Rep. 2020;40: BSR20192826.
• 21. Lai CS, Li S, Miyauchi Y, Suzawa M, Ho CT, Pan MH. Potent anti-cancer effects of citrus peel flavonoids in human prostate xenograft tumors. Food Funct. 2013;4:944.
• 22. Pratheeshkumar P, Son YO, Budhraja A, Wang X, Ding S, Wang L et al. Luteolin ınhibits human prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. PLoS One. 2012;7:e52279.
• 23. Shukla S, MacLennan GT, Fu P, Gupta S. Apigenin attenuates ınsulin-like growth factor-ı signaling in an autochthonous mouse prostate cancer model. pharm res. 2012;29:1506-17.
• 24. Shen KH, Hung SH, Yin LT, Huang CS, Chao CH, Liu CL et al. Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway. Mol Cell Biochem. 2010;333:279-91.
• 25. Chien CS, Shen KH, Huang JS, Ko SC, Shih YW. Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells. Mol Cell Biochem. 2010;333:169-80.
• 26. Vijayababu MR, Arunkumar A, Kanagaraj P, Venkataraman P, Krishnamoorthy G, Arunakaran J. Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3). Mol Cell Biochem. 2006;287:109-16.