Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study (Part II)

Abstract

In our previous work, the partitions (1 mg/mL) of Ageratum conyzoides (AC) aerial parts and Ixora coccinea (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC50 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 IC50 determinations for AC n-hexane, IC n-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 n-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC n-hexane, IC n-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC50 as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10−2 µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC n-hexane demonstrated IC50 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC50 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC50 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 IC50 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.

Turning Waste into Beneficial Resource: Implication of Ageratum conyzoides L. in Sustainable Agriculture, Environment and Biopharma Sectors

“…precocene I, β-sitosterol, precocene II, 6-vinyl-7-methoxy-2,2-dimethyl chromene (VMDC), stigmasterol, polymethoxyflavone, pyrrolizidine, neophytadiene, phytol, and caryophyllene isolated from ACE have been used to screen their potential application against various drug targets (e.g., MMP-9, p53, cox-2, α -amylase, etc.) for various diseases like malaria, diabetes, breast cancer and cervical cancer [ 75 – 78 ]. Recently, key secondary metabolites (e.g., Kaempferol, Quercetin, etc.)…”

“…Also, the level of MMP-9 expression is the key indicator of triple-negative breast cancer disease diagnosis. Recently, Hariono et al [ 78 ] used the n -hexane fraction of ACE to assess its inhibitory potential against MMP-9. The compound oxytetracycline (OTC) isolated from n -hexane fraction had a potent inhibitory effect against MMP-9 with IC 50 value of 246.1 µg/ mL.…”

“…Further, molecular docking analysis suggested that OTC inhibited MMP-9 activity by binding to the PEX9 domain rather than the catalytic site. Therefore, due to higher selective inhibition of MMP-9, OTC can be a safe and promising candidate against triple-negative breast cancer [ 78 ]. With the tremendous progress in advanced molecular technologies, more focused studies in the future would bring out numerous beneficial uses affirming biomedicinal properties of A. conyzoides .…”

In vitro Cytotoxic Potential of Sterculia quadrifida Leaf Extract Against Human Breast Cancer Cell Lines

“…10 Furthermore, the natural product is thought to have significant cytotoxic potential. 11 This study was aimed at investigating the potential of S. quadrifida leaf extract as a cytotoxic agent in breast cancer cells.…”

Potential SARS-CoV-2 3CLpro inhibitors from chromene, flavonoid and hydroxamic acid compound based on FRET assay, docking and pharmacophore studies

“…Our previous study reported some local plants demonstrating significant inhibition toward matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme having roles in extracellular matrix (ECM) degradation which facilitates in-cell migration related to cancer metastasis [34] , [35] . Since both MMP-9 and 3CLpro are proteolytic enzymes, this prompts us to explore the probability of these plants to be the 3CLpro inhibitor as well.…”