The Effect of Piperine on MMP-9, VEGF, and E-cadherin Expression in Breast Cancer MCF-7 Cell Line
Abstract
Background: Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and E-cadherin play a vital role in the behavior of angiogenesis, metastasis, and invasion of breast tumor cells. Piperine, the main component of Piper Nigrum, has shown anti-cancer properties in various malignancies. This Study investigates the potential effect of piperine on MMP-9, E-cadherin, and VEGF expression in breast cancer MCF-7 cell line. Methods: MTT assay was applied to assess the viability of MCF-7 cells. The mRNA levels of MMP-9, VEGF, and E-cadherin were assayed by qRT-PCR. Western blot was performed to identify the protein level of MMP-9. Results: MTT assay results showed that piperine treatment (5, 10, 25, 50, 75, and 100 μM) for 24 hours effectively inhibited cell viability of MCF-7 cells as compared with the control group. Furthermore, the gene expression of VEGF, MMP-9, and E-cadherin was dose-dependently suppressed by piperine treatment (5, 10 and 25 μM) (P<0.05; P<0.01). The results also indicated that piperine (5, 10, and 25 μM) significantly suppressed MMP-9 protein expression after 24 hours of piperine treatment (P<0.01). Conclusion: These results suggest that piperine may prevent angiogenesis, migration, and invasion of MCF-7 cells by suppressing MMP-9 and VEGF, and by inducing E-cadherin expression. Hence, it may be a suitable candidate for designing new drugs in cancer therapy.
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14. Samykutty A, Shetty AV, Dakshinamoorthy G, Bartik MM, Johnson GL, Webb B, et al. Piperine, a bioactive component of pepper spice exerts therapeutic effects on androgen dependent and androgen independent prostate cancer cells. PLoS One. 2013;8(6).
15. Zhang J, Zhu X, Li H, Li B, Sun L, Xie T, et al. Piperine piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression. International immunopharmacology. 2015;24(1):50-8.
16. Zeng Y, Yang Y. Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP‑9 signaling pathway in DU145 cells. Molecular medicine reports. 2018;17(5):6363-70.
17. Shafaei Z, Abazari O, Divsalar A, Ghalandari B, Poursoleiman A, Saboury AA, et al. Effect of a Synthesized Amyl-Glycine1, 10-Phenanthroline Platinum Nitrate on Structure and Stability of Human Blood Carrier Protein, Albumin: Spectroscopic and Modeling Approaches. J Fluoresc. 2017;27(5):1829-38.
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19. Musavi H, Abazari O, Barartabar Z, et al. The benefits of Vitamin D in the COVID-19 pandemic: biochemical and immunological mechanisms. Arch Physiol Biochem. 2020:1-9.
20. Rajoriya S, Nandhakumar P, Karthik K, Kumar A, Saini M, Kataria M. Study on effect of eugenol on anti-metastatic activity and expression of MMPS in TNBC MDA MB: 231 cell line. Journal of Pharmacognosy and Phytochemistry. 2019;8(4):788-94.
21. Deryugina EI, Quigley JP. Tumor angiogenesis: MMP-mediated induction of intravasation-and metastasis-sustaining neovasculature. Matrix Biology. 2015;44:94-112.
22. Akdeniz O, Akduman D, Haksever M, Ozkarakas H, Müezzinoglu B. Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, MMP-9 and E-cadherin. Asian Pac J Cancer Prev. 2013;14(9):5301-10.
23. Abazari O, Shafaei Z, Divsalar A, Eslami-Moghadam M, Ghalandari B, Saboury AA, et al. Interaction of the synthesized anti-cancer compound of the methyl-glycine 1, 10-phenanthroline platinum nitrate with human serum albumin and human hemoglobin proteins by spectroscopy methods and molecular docking. Journal of the Iranian Chemical Society. 2020:1-14.
24. Doucette CD, Hilchie AL, Liwski R, Hoskin DW. Piperine, a dietary phytochemical, inhibits angiogenesis. The Journal of nutritional biochemistry. 2013;24(1):231-9.
25. Ouyang D-y, Zeng L-h, Pan H, Xu L-h, Wang Y, Liu K-p, et al. Piperine piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy. Food and chemical toxicology. 2013;60:424-30.
26. Winer A, Adams S, Mignatti P. Matrix metalloproteinase inhibitors in cancer therapy: turning past failures into future successes. Molecular cancer therapeutics. 2018;17(6):1147-55.
27. Mohamed FE-ZA, Toni ND. Caveolin-1 Expression Together with VEGF can be a Predictor for Lung Metastasis and Poor Prognosis in Osteosarcoma. Pathology & Oncology Research. 2019:1-8.
28. Kuerti S, Oliveira-Ferrer L, Milde-Langosch K, Schmalfeldt B, Legler K, Woelber L, et al. VEGF-C expression attributes the risk for lymphatic metastases to ovarian cancer patients. Oncotarget. 2017;8(26):43218.
29. Zare Z, Dizaj TN, Lohrasbi A, et al. Silibinin inhibits TGF-β-induced MMP-2 and MMP-9 through Smad Signaling pathway in colorectal cancer HT-29 cells. Basic Clin Cancer Res. 2020;12(2):79-88.
30. Ji Q, Liu X, Han Z, Zhou L, Sui H, Yan L, et al. Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression. BMC cancer. 2015;15(1):97.
31. Abazari O, Divsalar A, Ghobadi R. Inhibitory effects of oxali-Platin as a chemotherapeutic drug on the function and structure of bovine liver catalase. J Biomol Struct Dyn. 2020;38(2):609-15.
2. Scully OJ, Bay B-H, Yip G, Yu Y. Breast cancer metastasis. Cancer Genomics-Proteomics. 2012;9(5):311-20.
3. Steigedal TS, Toraskar J, Redvers RP, Valla M, Magnussen SN, Bofin AM, et al. Nephronectin is correlated with poor prognosis in breast cancer and promotes metastasis via its integrin-binding motifs. Neoplasia. 2018;20(4):387-400.
4. Mehner C, Hockla A, Miller E, Ran S, Radisky DC, Radisky ES. Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget. 2014;5(9):2736.
5. Canel M, Serrels A, Frame MC, Brunton VG. E-cadherin–integrin crosstalk in cancer invasion and metastasis. Journal of cell science. 2013;126(2):393-401.
6. Abbasi M, Abazari OO. Probing the Biological evaluations of a new designed Palladium (II) complex using spectroscopic and theoretical approaches: Human Hemoglobin as a Target. Arch Med Lab Sci. 2018;3(3).
7. Musavi H, Fattah A, Abbasi M. Differential Expression of the KLK2 and KLK3 Genes in Peripheral Blood and Tissues Samples of Iranian Patients with Prostate Cancer. Medical Laboratory Journal. 2019;13(3):25-30.
8. Claesson‐Welsh L, Welsh M. VEGFA and tumour angiogenesis. Journal of internal medicine. 2013;273(2):114-27.
9. Sennino B, Ishiguro-Oonuma T, Wei Y, Naylor RM, Williamson CW, Bhagwandin V, et al. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer discovery. 2012;2(3):270-87.
10. Abazari O, Divsalar A, Ghobadi R. Inhibitory effects of oxali-Platin as a chemotherapeutic drug on the function and structure of bovine liver catalase. J Biomol Struct Dyn. 2019:1-7.
11. Shityakov S, Bigdelian E, Hussein AA, Hussain MB, Tripathi YC, Khan MU, et al. Phytochemical and pharmacological attributes of piperine: A bioactive ingredient of black pepper. European journal of medicinal chemistry. 2019.
12. Asadi A, Nezhad DY, Javazm AR, Khanicheragh P, Mashouri L, Shakeri F, et al. In vitro Effects of Curcumin on Transforming Growth Factor-β-mediated Non-Smad Signaling Pathway, Oxidative Stress, and Pro‐inflammatory Cytokines Production with Human Vascular Smooth Muscle Cells. Iran J Allergy Asthma Immunol. 2019:1-10.
13. Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a potential anti-cancer agent: a review on preclinical studies. Current medicinal chemistry. 2019.
14. Samykutty A, Shetty AV, Dakshinamoorthy G, Bartik MM, Johnson GL, Webb B, et al. Piperine, a bioactive component of pepper spice exerts therapeutic effects on androgen dependent and androgen independent prostate cancer cells. PLoS One. 2013;8(6).
15. Zhang J, Zhu X, Li H, Li B, Sun L, Xie T, et al. Piperine piperine inhibits proliferation of human osteosarcoma cells via G2/M phase arrest and metastasis by suppressing MMP-2/-9 expression. International immunopharmacology. 2015;24(1):50-8.
16. Zeng Y, Yang Y. Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP‑9 signaling pathway in DU145 cells. Molecular medicine reports. 2018;17(5):6363-70.
17. Shafaei Z, Abazari O, Divsalar A, Ghalandari B, Poursoleiman A, Saboury AA, et al. Effect of a Synthesized Amyl-Glycine1, 10-Phenanthroline Platinum Nitrate on Structure and Stability of Human Blood Carrier Protein, Albumin: Spectroscopic and Modeling Approaches. J Fluoresc. 2017;27(5):1829-38.
18. Mukherjee S, Mazumdar M, Chakraborty S, Manna A, Saha S, Khan P, et al. Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop. Stem cell research & therapy. 2014;5(5):116.
19. Musavi H, Abazari O, Barartabar Z, et al. The benefits of Vitamin D in the COVID-19 pandemic: biochemical and immunological mechanisms. Arch Physiol Biochem. 2020:1-9.
20. Rajoriya S, Nandhakumar P, Karthik K, Kumar A, Saini M, Kataria M. Study on effect of eugenol on anti-metastatic activity and expression of MMPS in TNBC MDA MB: 231 cell line. Journal of Pharmacognosy and Phytochemistry. 2019;8(4):788-94.
21. Deryugina EI, Quigley JP. Tumor angiogenesis: MMP-mediated induction of intravasation-and metastasis-sustaining neovasculature. Matrix Biology. 2015;44:94-112.
22. Akdeniz O, Akduman D, Haksever M, Ozkarakas H, Müezzinoglu B. Relationships between clinical behavior of laryngeal squamous cell carcinomas and expression of VEGF, MMP-9 and E-cadherin. Asian Pac J Cancer Prev. 2013;14(9):5301-10.
23. Abazari O, Shafaei Z, Divsalar A, Eslami-Moghadam M, Ghalandari B, Saboury AA, et al. Interaction of the synthesized anti-cancer compound of the methyl-glycine 1, 10-phenanthroline platinum nitrate with human serum albumin and human hemoglobin proteins by spectroscopy methods and molecular docking. Journal of the Iranian Chemical Society. 2020:1-14.
24. Doucette CD, Hilchie AL, Liwski R, Hoskin DW. Piperine, a dietary phytochemical, inhibits angiogenesis. The Journal of nutritional biochemistry. 2013;24(1):231-9.
25. Ouyang D-y, Zeng L-h, Pan H, Xu L-h, Wang Y, Liu K-p, et al. Piperine piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy. Food and chemical toxicology. 2013;60:424-30.
26. Winer A, Adams S, Mignatti P. Matrix metalloproteinase inhibitors in cancer therapy: turning past failures into future successes. Molecular cancer therapeutics. 2018;17(6):1147-55.
27. Mohamed FE-ZA, Toni ND. Caveolin-1 Expression Together with VEGF can be a Predictor for Lung Metastasis and Poor Prognosis in Osteosarcoma. Pathology & Oncology Research. 2019:1-8.
28. Kuerti S, Oliveira-Ferrer L, Milde-Langosch K, Schmalfeldt B, Legler K, Woelber L, et al. VEGF-C expression attributes the risk for lymphatic metastases to ovarian cancer patients. Oncotarget. 2017;8(26):43218.
29. Zare Z, Dizaj TN, Lohrasbi A, et al. Silibinin inhibits TGF-β-induced MMP-2 and MMP-9 through Smad Signaling pathway in colorectal cancer HT-29 cells. Basic Clin Cancer Res. 2020;12(2):79-88.
30. Ji Q, Liu X, Han Z, Zhou L, Sui H, Yan L, et al. Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression. BMC cancer. 2015;15(1):97.
31. Abazari O, Divsalar A, Ghobadi R. Inhibitory effects of oxali-Platin as a chemotherapeutic drug on the function and structure of bovine liver catalase. J Biomol Struct Dyn. 2020;38(2):609-15.
| Files | ||
| Issue | Vol 12 No 3 (2020) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v12i3.5767 | |
| Keywords | ||
| Piperine MCF-7 MMP-9 VEGF E-cadherin | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Zare Z, Nayerpour Dizaj T, Lohrasbi A, Sheikhalishahi ZS, Panji M, Hosseinabadi F, Najafi V, Abazari O, Abbasi M, Khanicheragh P. The Effect of Piperine on MMP-9, VEGF, and E-cadherin Expression in Breast Cancer MCF-7 Cell Line. Basic Clin Cancer Res. 2021;12(3):112-119.
