Abstract
Spirulina platensis :have been studied for several biological activities. In the current study C-phycocyanin containing protein extract (C-PC extract) of Spirulina platensis have been studied for its effect on human matrix metalloproteinases (MMP-1, MMP-2 and MMP-9) and tissue inhibitors of MMPs (TIMP-1 and TIMP-2). In the present study, breast cancer cell line (MDA-MB 231) and hepatocellular cancer cell line (HepG2) were examined for inhibition of MMPs at different levels of expression after C-PC extract treatment. Herein, we have demonstrated that C-PC extract significantly reduced activity of MMP-2 by 55.13% and MMP-9 by 57.9% in HepG2 cells at 15 μg concentration. Additionally, the treatment has reduced mRNA expression of MMP-2 and MMP-9 at 20 μg concentration by 1.65-folds and 1.66-folds respectively. The C-PC extract treatment have also downregulated a mRNA expression of TIMP-2 by 1.12 folds at 20 μg concentration in HepG2 cells. Together, these results indicate that C-PC, extract successfully inhibited MMP-2 and -9 at different levels of expression and TIMP-2 at a mRNA expression level; however, extract did not have any effect on MMP-1 expressed in MDA-MB231 and TIMP-1 expressed in HepG2 cells as well as the exact mechanism of inhibition of MMP-2, MMP-9 and TIMP-2 remained unclear.
Similar content being viewed by others
Abbreviations
- MMP:
-
Matrix metalloproteinases
- TIMP:
-
Tissue inhibitors of matrix metalloproteinases
- C-PC extract:
-
C-phycocyanin containing protein extract
- MMPI:
-
Matrix metalloproteinases inhibitors
- MDA-MB231:
-
Breast cancer cell line
- HepG2:
-
Hepatocellular cancer cell line
- ECM:
-
Extracellular matrix
- MT1-MMP (MMP-14):
-
Membrane type matrix metalloproteinase-14
References
Desai K, Subramanian S (2004) Spirulina: the wonder food of the 21st Century. Asia Pac Biotech News 8:1298–1302
Miranda MS, Cintra RG, Barros SB, Mancini Filho J (1998) Antioxidant activity of the microalga Spirulina maxima. Brazilian J Med Biol Res 31:1075–1079
Ayehunie S, Belay A, Baba TW, Ruprecht RM (1998) Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis). J Acquir Immune Defic Syndr Hum Retrovirol 18:7–12
Chen Y, Chang G, Kuo S, Huang S, Hu Ic, Lo Y, Shih S (2016) Well-tolerated Spirulina extract inhibits influenza virus replication and reduces virus-induced mortality. Sci Rep 6:1–11
AbdelDaim MM, Farouk SM, Madkour FF, Azab SS (2015) Anti-inflammatory and immunomodulatory effects of Spirulina platensis in comparison to Dunaliella salina in acetic acid-induced rat experimental colitis. Immunopharmacol Immunotoxicol 37:126–139
Pérez-Juárez A, Chamorro G, Alva-Sánchez C, Paniagua-Castro N, Pacheco-Rosado J (2016) Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid-neuronal death. Pharm Biol 54:1408–1412
Samuels R, Mani U, Iyer U, Nayak U (2002) Hypocholesterolemic effect of spirulina in patients with hyperlipidemic nephrotic syndrome. J Med Food 5:91–96
Kepekçi RA, Polat S, Çelik A, Bayat N, Saygideger SD (2013) Protective effect of Spirulina platensis enriched in phenolic compounds against hepatotoxicity induced by CCl4. Food Chem 141:1972–1979
Mitra S, Siddiqui WA, Khandelwal S (2015) C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: a comparative efficacy evaluation with N-acetyl cysteine in adult rat brain. Chem Biol Interact 238:138–150
Zhang F, Lu J, Zhang J, Xie J (2015) Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPTP-induced Parkinson’s disease model in C57BL/6 J mice. Neural Regen Res 10:308–313
Patel A, Mishra S, Ghosh PK (2006) Antioxidant potential of C-phycocyanin isolated from cyanobacterial species Lyngbya, Phormidium and Spirulina spp. Indian J Biochem Biophys 43:25–31
Gantar M, Dhandayuthapani S RA (2012) Phycocyanin induces apoptosis and enhances the effect of topotecan on prostate cell line LNCaP. J Med Food 15:1091–1095
Madhyastha HK, Radha KS, Nakajima Y, Omura S, Maruyama M (2008) uPA dependent and independent mechanisms of wound healing by C-phycocyanin. J Cell Mol Med 12:2691–2703
Farooq SM, Boppana NB, Devarajan A, Asokan D, Sekaran SD, Shankar EM, Li C, Gopal K, Bakar SA, Karthik HS, Ebrahim AS (2014) C-phycocyanin confers protection against oxalate-mediated oxidative stress and mitochondrial dysfunctions in MDCK cells. PLoS ONE 9:1–9
Li B, Gao MH, Chu XM, Teng L, Lv CY, Yang P YQ (2015) The synergistic antitumor effects of all-trans retinoic acid and C-phycocyanin on the lung cancer A549 cells in vitro and in vivo. Eur J Pharmacol 15:107–114
Loffek S, Schilling O, Franzke C (2011) Biological role of matrix metalloproteinases: a critical balance. Eur Respir J 38:191–208
Liang J, Wu S, Lo H, Hsiang C, Ho T (2009) Vanillin inhibits matrix metalloproteinase-9 expression through down-regulation of nuclear factor-kappaB signaling pathway in human hepatocellular carcinoma cells. Mol Pharmacol 75:151–157
Liu H, Kato Y, Erzinger SA, Kiriakova GM, Qian Y, Palmieri D, Steeg PS, Price JE (2012) The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model. BMC Cancer 12:583–594
Sun S, BayJensen A, Karsdal MA, Siebuhr AS, Zheng Q, Maksymowych WP, Christiansen TG, Henriksen K (2014) The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases. BMC Musculoskelet Disord 15:93–101
Halade GV, Jin Y, Lindsey ML (2013) Matrix metalloproteinase (MMP)-9: a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation. Pharmacol Ther 139:32–40
Radisky ES, Radisky DC (2015) Matrix metalloproteinases as breast cancer drivers and therapeutic targets. Front Biosci 20:1144–1163
Nuti E, Tuccinardi T, Rossello A (2007) Matrix metalloproteinase inhibitors: new challenges in the era of post broad-spectrum inhibitors. Curr Pharm Des 13:2087–2100
Patel A, Mishra S, Pawar R, Ghosh P (2005) Purification and characterization of C-Phycocyanin from cyanobacterial species of marine and freshwater habitat. Protein Expr Purif 40:248–255
Bennett A, Bogorad L (1973) Complementary chromatic adaptation in a filamentous blue-green alga. J Cell Biol 58:419–435
Omanakuttan A, Nambiar J, Harris RM, Bose C, Pandurangan N, Varghese RK, Kumar GB, Tainer JA, Banerji A, Jefferson J, Perry P, Nair BG (2012) Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9. Mol Pharmacol 82:614–622.
Pengfei Lu KT, Weaver VM, Werb and Z (2011) Extracellular matrix degradation and remodeling in development and disease. Addit Perspect Extracell Matrix Biol 3:1–24
Zhang L, Morrison AJ, Thibodeau PH (2015) Interdomain contacts and the stability of Serralysin Protease from Serratia marcescens. PLoS ONE 10:e0138419
Herszényi L, Hritz I, Lakatos G, Varga MZ, Tulassay Z (2012) The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer. Int J Mol Sci 13:13240–13263
MiliaArgeiti E, Huet E, Labropoulou VT, Mourah S, Fenichel P, Karamanos NK, Menashi S, Theocharis AD (2012) Imbalance of MMP-2 and MMP-9 expression versus TIMP-1 and TIMP-2 reflects increased invasiveness of human testicular germ cell tumours. Int J Androl 35:835–844
Halder SK, Osteen KG, AlHendy A (2013) Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum Reprod 28:2407–2416
Bendardaf R, Buhmeida A, Ristamäki R, Syrjänen K, Pyrhönen S (2007) MMP-1 (collagenase-1) expression in primary colorectal cancer and its metastases. Scand J Gastroenterol 42:1473–1478
Endo H, Watanabe T, Sugioka Y, Niioka M, Inagaki Y, Okazaki I (2009) Activation of two distinct MAPK pathways governs constitutive expression of matrix metalloproteinase-1 in human pancreatic cancer cell lines. Int J Oncol 35:1237–1245
Peng H, Zhang X, Cao P (2012) MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma. Brazilian J Med Biol 45:86–92
Yamada H, Yoneda M, Gosho M, Kato T, Zako M (2016) Bimatoprost, latanoprost, and tafluprost induce differential expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases. BMC Ophthalmol 16:1–6
Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer trials and tribulations. Science 295:2387–2392
Fan Z, Duan X, Cai H, Wang L, Li M, Qu J, Li W, Wang Y, Wang J (2015) Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway. Oncol Rep 34:691–698
Huang S, Yang R, Wu H, Wang C, Pang JS (2011) Zinc-chelation contributes to the anti-angiogenic effect of ellagic acid on inhibiting MMP-2 activity, cell migration and tube formation. PLoS One 6:1–11
Newsome AL, Johnson JP, Seipelt RL, Thompson MW (2007) Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by zinc chelation. Biochem Cell Biol 85:563–572
Hassan ZK, Daghestani MH (2012) Curcumin effect on MMPs and TIMPs genes in a breast cancer cell line. Asian Pac J Cancer Prev 13:3259–3264.
Hamze AB, Wei S, Bahudhanapati H, Kota S, Acharya KR, Brew K (2007) Constraining specificity in the N-domain of tissue inhibitor of metalloproteinases-1; gelatinase-selective inhibitors. Protein Sci 16:1905–1913
Morgunova E, Tuuttila A, Bergmann U, Tryggvason K, Huber R (2002) Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc Natl Acad Sci USA 99:7414–7419
Würtz SØ, Würtz SØ, Schrohl A-S, Mouridsen H, Brünner N (2008) TIMP-1 as a tumor marker in breast cancer—an update. Acta Oncol 47:580–590.
Nalluri S, Ghoshal-Gupta S, Kutiyanawalla A, Gayatri S, Lee BR, Jiwani S, Rojiani AM, Rojiani MV (2015) TIMP-1 inhibits apoptosis in lung adenocarcinoma cells via interaction with Bcl-2. PLoS ONE 10:1–14
Roeb E, Bosserhoff AK, Hamacher S, Jansen B, Dahmen J, Wagner S, Matern S (2005) Enhanced migration of tissue inhibitor of metalloproteinase overexpressing hepatoma cells is attributed to gelatinases: relevance to intracellular signaling pathways. World J Gastroenterol 11:1096–1104
Valente P, Fassina G, Melchiori A, Masiello L, Cilli M, Vacca A, Onisto M, Santi L, StetlerStevenson WG, Albini A (1998) TIMP-2 over-expression reduces invasion and angiogenesis and protects B16F10 melanoma cells from apoptosis. Int J cancer 75:246–253
Kai AK, Chan LK, Lo RC, Lee JM, Wong CC, Wong JC, Ng IO (2016) Down-regulation of TIMP2 by HIF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma. Hepatology 64:473–487
Park BC, Thapa D, Lee Y, Kwak M, Lee E, Choi HG, Yong CS, Kim J (2007) 1-furan-2-yl-3-pyridin-2-yl-propenone inhibits the invasion and migration of HT1080 human fibrosarcoma cells through the inhibition of proMMP-2 activation and down regulation of MMP-9 and MT1-MMP. Eur J Pharmacol 567:193–197
Xu X, Mikhailova M, Chen Z, Pal S, Robichaud TK, Lafer EM, Baber S, Steffensen B (2011) Peptide from the C-terminal domain of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) inhibits membrane activation of matrix metalloproteinase-2 (MMP-2). Matrix Biol 30:404–412
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical Approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Kunte, M., Desai, K. The Inhibitory Effect of C-phycocyanin Containing Protein Extract (C-PC Extract) on Human Matrix Metalloproteinases (MMP-2 and MMP-9) in Hepatocellular Cancer Cell Line (HepG2). Protein J 36, 186–195 (2017). https://doi.org/10.1007/s10930-017-9707-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10930-017-9707-0