Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II)
In our previous work, the partitions (1 mg/mL) of <i>Ageratum conyzoides</i> (AC) aerial parts and <i>Ixora coccinea</i> (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC<sub>50</sub> 43 and 116 µg/mL, respectively, tow...
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2021-03-01
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author | Maywan Hariono Rollando Rollando I Yoga Abraham Harjono Alfonsus Suryodanindro Michael Yanuar Thomas Gonzaga Zet Parabang Pandu Hariyono Rifki Febriansah Adi Hermawansyah Wahyuning Setyani Habibah Wahab |
author_facet | Maywan Hariono Rollando Rollando I Yoga Abraham Harjono Alfonsus Suryodanindro Michael Yanuar Thomas Gonzaga Zet Parabang Pandu Hariyono Rifki Febriansah Adi Hermawansyah Wahyuning Setyani Habibah Wahab |
author_sort | Maywan Hariono |
collection | DOAJ |
description | In our previous work, the partitions (1 mg/mL) of <i>Ageratum conyzoides</i> (AC) aerial parts and <i>Ixora coccinea</i> (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC<sub>50</sub> 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present study, we performed IC<sub>50</sub> determinations for AC <i>n</i>-hexane, IC <i>n</i>-hexane, and IC ethylacetate partitions, followed by the cytotoxicity study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC <i>n</i>-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC <i>n</i>-hexane, IC <i>n</i>-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC<sub>50</sub> as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10<sup>−2</sup> µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC <i>n</i>-hexane demonstrated IC<sub>50</sub> 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC<sub>50</sub> 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC<sub>50</sub> 18.69 µM, whereas DOP was inactive. A molecular docking study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC<sub>50</sub> 414.20 µM. In conclusion, this study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents. |
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spelling | doaj.art-32f567fcbe384895b41b35decb7b21b52023-11-21T09:35:46ZengMDPI AGMolecules1420-30492021-03-01265146410.3390/molecules26051464Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II)Maywan Hariono0Rollando Rollando1I Yoga2Abraham Harjono3Alfonsus Suryodanindro4Michael Yanuar5Thomas Gonzaga6Zet Parabang7Pandu Hariyono8Rifki Febriansah9Adi Hermawansyah10Wahyuning Setyani11Habibah Wahab12Drug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaBachelor in Pharmacy Program, Faculty of Science and Technology, Ma Chung University, Malang 65151, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaSchool of Pharmacy, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Kasihan, Bantul, Yogyakarta 55183, IndonesiaCell Culture Laboratory, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Kasihan, Bantul, Yogyakarta 55183, IndonesiaDrug Discovery Student Club, Faculty of Pharmacy, Campus III, Sanata Dharma University, Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282, IndonesiaPharmaceutical Technology Department, School of Pharmaceutical Sciences and USM-RIKEN Centre for Ageing Science (URICAS), Universiti Sains Malaysia, Minden, Pulau Pinang 11800, MalaysiaIn our previous work, the partitions (1 mg/mL) of <i>Ageratum conyzoides</i> (AC) aerial parts and <i>Ixora coccinea</i> (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC<sub>50</sub> 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present study, we performed IC<sub>50</sub> determinations for AC <i>n</i>-hexane, IC <i>n</i>-hexane, and IC ethylacetate partitions, followed by the cytotoxicity study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC <i>n</i>-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC <i>n</i>-hexane, IC <i>n</i>-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC<sub>50</sub> as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10<sup>−2</sup> µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC <i>n</i>-hexane demonstrated IC<sub>50</sub> 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC<sub>50</sub> 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC<sub>50</sub> 18.69 µM, whereas DOP was inactive. A molecular docking study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC<sub>50</sub> 414.20 µM. In conclusion, this study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents.https://www.mdpi.com/1420-3049/26/5/1464MMP9PEX9cancerbioguidedfractionationageratum |
spellingShingle | Maywan Hariono Rollando Rollando I Yoga Abraham Harjono Alfonsus Suryodanindro Michael Yanuar Thomas Gonzaga Zet Parabang Pandu Hariyono Rifki Febriansah Adi Hermawansyah Wahyuning Setyani Habibah Wahab Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II) Molecules MMP9 PEX9 cancer bioguided fractionation ageratum |
title | Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II) |
title_full | Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II) |
title_fullStr | Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II) |
title_full_unstemmed | Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II) |
title_short | Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II) |
title_sort | bioguided fractionation of local plants against matrix metalloproteinase9 and its cytotoxicity against breast cancer cell models in silico and in vitro study part ii |
topic | MMP9 PEX9 cancer bioguided fractionation ageratum |
url | https://www.mdpi.com/1420-3049/26/5/1464 |
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