Sterculia foetida Leaf Fraction Against Matrix Metalloproteinase-9 Protein and 4T1 Breast Cancer Cells: In-Vitro and In-Silico Studies
doi.org/10.26538/tjnpr/v5i1.15
Keywords:
Sterculia foetida, Fraction, Cytotoxic, MMP-9, 4T1, PEX9Abstract
Sterculia foetida leaf extract has been shown to have cytotoxic activity. Matrix metalloproteinase-9 (MMP-9) has an important role in pathophysiological functions. Inhibition of MMP9 is an important therapeutic approach for combating cancer. This study was conducted to determine the most active fraction of S. foetida as anti-breast cancer agent with hemopexin-like domain of MMP-9 (PEX9) as the selective protein target and 4T1 cells line as metastatic breast cancer cell. The leaves S. foetida was extracted using 80% methanol and was fractionated into fractions of n-hexane, chloroform, ethyl acetate, n-butanol, and insoluble n-butanol with liquid-liquid partition. In vitro screening against MMP-9 was performed using FRET-based assay and cytotoxic tests were performed using the MTT assay. Identification of compounds in the most active fraction using GC-MS. The docking to PEX9 was run using AutoDock Vina embedded in PyRx program. The n-hexane fraction was the most active fraction to inhibit MMP-9 with an IC50 of 19.67 µg/mL and inhibit the growth of 4T1 cells with an IC50 of 34.65µg/mL. NNGH was used as positive control for the in-vitro and in-silico studies. The GC-MS results of the n-hexane fraction showed that there were 23 compounds, and they had binding affinity score of -8.9 to -4.9 kcal/mol towards PEX9. It can be concluded that S. foetida leaf has the potential to be developed for therapeutic use, especially for breast cancer therapy.
References
de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020; 8(2):e180-90.
Carioli G, Malvezzi M, Bertuccio P, Hashim D, Waxman S, Negri E, Boffetta P, La Vecchia C. Cancer mortality in the elderly in 11 countries worldwide, 1970–2015. Ann Oncol. 2019; 30(8):1344-1355.
Gaddam S, Heller SL, Babb JS, Gao Y. Male Breast Cancer Risk Assessment and Screening Recommendations in High-Risk Men Who Undergo
Genetic Counseling and Multigene Panel Testing. Clin Breast Cancer [Internet]. 2020 Jul 25 [cited 2020 Nov 28]; Available from: http://www.sciencedirect.com/science/article/pii/S1526820920301804
Panieri E. Breast cancer screening in developing countries. Best Pract Res Clin Obstet Gynaecol. 2012; 26(2):283-90.
Graafland L, Abbott M, Accordino M. Breast Cancer Risk Related to Combined Oral Contraceptive Use. J Nurse Pract. 2020; 16(2):116-20.
Mondal S, Adhikari N, Banerjee S, Amin SA, Jha T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur J Med Chem. 2020;194:112260.
Kessenbrock K, Wang C-Y, Werb Z. Matrix metalloproteinases in stem cell regulation and cancer. Matrix Biol. 2015; 44(46):184-90.
Mohammadian H, Sharifi R, Rezanezhad Amirdehi S, Taheri E, Babazadeh Bedoustani A. Matrix metalloproteinase MMP1 and MMP9 genes expression in breast cancer tissue. Gene Rep. 2020; 21:100906.
Xu T, Zhang S, Qiu D, Li X, Fan Y. Association between matrix metalloproteinase 9 polymorphisms and breast cancer risk: An updated meta-analysis and trial sequential analysis. Gene. 2020; 759:144972.
Omoruyi SI, Kangwa TS, Ibrakaw AS, Cupido CN, Marnewick JL, Ekpo OE. Cytotoxic activities of selected plants of the family Amaryllidaceae on brain tumour cell lines. South Afr J Bot [Internet]. 2020 Sep 18 [cited 2020 Nov 28]; Available from: http://www.sciencedirect.com/science/article/pii/S025462992031071
Grujičić D, Marković A, Vukajlović JT, Stanković M, Jakovljević MR, Ćirić A. Genotoxic and cytotoxic properties of two medical plants (Teucrium arduini L.and Teucrium flavum L.) in relation to their polyphenolic contents. Mutat Res Toxicol Environ Mutagen. 2020;
:503168.
Jafri A, Bano S, Rais J, Khan F, Shivnath N, Sharma AK. Phytochemical screening of Sterculia foetida seed extract for anti-oxidant, anti-microbial activity, and detection of apoptosis through reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP)
decrease, and nuclear fragmentation in human osteosarcoma cells. J Histotechnol. 2019; 42(2):68-79.
Mujumdar AM, Naik DG, Waghole RJ, Kulkarni DK, Kumbhojkar MS. Pharmacological studies on Sterculia foetida leaves. Pharm Biol. 2000; 38(1):13-7.
Rajasekharreddy P and Rani PU. Biofabrication of Ag nanoparticles using Sterculia foetida L. seed extract and their toxic potential against mosquito vectors and HeLa cancer cells. Mater Sci Eng C Mater Biol Appl. 2014; 39:203-12.
Hariono M, Nuwarda RF, Yusuf M, Rollando R, Jenie RI, Al-Najjar B. Arylamide as Potential Selective Inhibitor for Matrix Metalloproteinase 9 (MMP9): Design, Synthesis, Biological Evaluation, and Molecular Modeling. J Chem Inf Model. 2020; 60(1):349-59.
Hariono M, Rollando R, Karamoy J, Hariyono P, Atmono M, Djohan M. Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study. Mol Basel Switz. 2020; 25(20): 4691
Rollando R. Combination of Hedyotis corymbosa L. and Tinospora crispa ethanolic extract increase cisplatin cytotoxicity on t47d breast cancer cells. Asian J Pharm Clin Res. 2018; 171-7.
Cha H, Kopetzki E, Huber R, Lanzendörfer M, Brandstetter H. Structural Basis of the Adaptive Molecular Recognition by MMP9. J Mol Biol. 2002; 320(5):1065-79.
Shokoohinia Y, Gheibi S, Kiani A, Sadrjavadi K, Nowroozi A, Shahlaei M. Multi-spectroscopic and molecular modeling investigation of the interactions between prantschimgin and matrix metalloproteinase 9 (MMP9). Lumin J Biol Chem Lumin. 2016; 31(2):587-93.
Kiani A, Almasi K, Shokoohinia Y, Sadrjavadi K, Nowroozi A, Shahlaei M. Combined spectroscopy and molecular modeling studies on the binding of galbanic acid and MMP9. Int J Biol Macromol. 2015; 81:308-15.
Shakeel E, Akhtar S, Khan MKA, Lohani M, Arif JM, Siddiqui MH. Molecular docking analysis of aplysin analogs targeting survivin protein. Bioinformation. 2017; 13(9):293-300.
Dufour A, Sampson NS, Li J, Kuscu C, Rizzo RC, Deleon JL. Small-molecule anticancer compounds selectively target the hemopexin domain of matrix metalloproteinase-9. Cancer Res. 2011; 71(14):4977-88.
Varbanov HP, Kuttler F, Banfi D, Turcatti G, Dyson PJ. Repositioning approved drugs for the treatment of problematic cancers using a screening approach. PloS One. 2017; 12(2):e0171052.
Braga RC and Andrade CH. Assessing the performance of 3D pharmacophore models in virtual screening: how good are they?. Curr Top Med Chem. 2013; 13(9):1127-38.
Rowsell S, Hawtin P, Minshull CA, Jepson H, Brockbank SM, Barratt DG, Slater AM, McPheat WL, Waterson D, Henney AM, Pauptit RA. Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor. J Mol Biol. 2002; 319(1):173-81.
Bai XY, Li S, Wang M, Li X, Yang Y, Xu Z, Li B, Li Y, Xia K, Chen H, Wu H. Krüppel-like factor 9 downregulates matrix metalloproteinase 9 transcription and suppresses human breast cancer invasion. Cancer Lett. 2018; 412:224-35.
Chi GF, Sop RVT, Mbaveng AT, Omollo Ombito J, Fotso GW, Nguenang GS, Kuete V, Efferth T, Ngadjui BT. Steroidal saponins from Raphia vinifera and their cytotoxic activity. Steroids. 2020; 163:108724.
Wang JN, Zhang ZY, Sun P, Cao DH, Xiao YD, Shi XC, Xiao CF, Hu HB, Xu Y. Four new steroids from the leaves and twigs of Dysoxylum pallens and their cytotoxic activities. Fitoterapia. 2020; 146:104696.
Yu JH, Yu SJ, Liu KL, Wang C, Liu C, Sun JY, Zhang H. Cytotoxic ergostane-type steroids from Ganoderma lingzhi. Steroids. 2021; 165:108767.
Kim M and Kim YB. A network-based pharmacology study of active compounds and targets of Fritillaria thunbergii against influenza. Comput Biol Chem. 2020;89:107375.
Khan MR and Mlungwana SM. γ-Sitosterol, a cytotoxic sterol from Markhamia zanzibarica and Kigelia africana. Fitoterapia. 1999; 70(1):96-7.
Sundarraj S, Thangam R, Sreevani V, Kaveri K, Gunasekaran P, Achiraman S, Kannan S. γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells. J Ethnopharmacol. 2012; 141(3):803-9.
Bednarczyk-Cwynar B, Wiecaszek T, Ruszkowski P. Cytotoxic Activity of Some Lupeol Derivatives. Nat Prod Commun. 2016; 11(9):1237-8.
Moriarity DM, Huang J, Yancey CA, Zhang P, Setzer WN, Lawton RO, Bates RB, Caldera S. Lupeol is the cytotoxic principle in the leaf extract of Dendropanax cf. querceti. Planta Med. 1998; 64(4):370-2.
Nguyen AT, Malonne H, Duez P, Vanhaelen-Fastre R, Vanhaelen M, Fontaine J. Cytotoxic constituents from Plumbago zeylanica. Fitoterapia. 2004; 75(5):500-4.
Ogunlaja OO, Moodley R, Singh M, Baijnath H, Jonnalagadda SB. Cytotoxic activity of the bioactive principles from Ficus burtt-davyi. J Environ Sci Health B. 2018; 53(4):261-75.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
