Antimigratory Activity of Brazilin-Containing Fraction from Caesalpinia sappan L. on MDAMB-231 Cells

Handayani, Sri; Susidarti, Ratna Asmah; Lotulung, Puspa Dewi; Darmawan, Akhmad; Meiyanto, Edy; Jenie, Riris Istighfari

doi:10.4308/hjb.27.4.266

Cited by 4 publications

(9 citation statements)

References 26 publications

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“…Extraction is carried out in Citrus House, Cancer Chemoprevention Research Center (CCRC), Faculty of Pharmacy, Universitas Gadjah Mada, Indonesia. The method was based on the previous reports of our research group (Handayani, et al, 2016;Haryanti, et al, 2017;Jenie, et al, 2020;Handayani, et al, 2020). Sappan wood simplicia was obtained from the Center for Research and Development of Traditional Medicinal and Medicinal Plants (B2P2TOOT) Tawangmangu, Jawa Tengah, Indonesia and has been determined to be a Caesalpinia sappan L. Before extraction, the sappan wood was ground to reduce the size of the sappan wood and sieved using a 40 sieved mesh to obtain a uniform size of sawdust.…”

Section: Sappan Wood Extraction (Swe) By Maceration Methodsmentioning

confidence: 99%

“…We performed the extraction based on Hung, et al (2014) report, which shows that methanolic extract of C. sappan exhibits potent inhibitory activity against various cancers cell lines, especially against HeLa cells. Other studies from our research group also used methanolic extract in highly metastatic cancer cells (Handayani, et al, 2016;Haryanti, et al, 2017;Jenie, et al, 2018;Handayani, et al, 2020).…”

Section: Sappan Wood Extraction (Swe) By Maceration Methodsmentioning

confidence: 99%

“…Sappan wood (Caesalpinia sappan L.) is one of the plants containing potential compounds as chemoprevention that promise cytotoxic and anti-MMP activities in various highly metastatic cancer cell lines such as MDA-MB-231, 4T1, MCF-7/HER2, and T47D (Hsieh, et al, 2013;Handayani, et al, 2016;Haryanti, et al, 2017;Jenie, et al, 2020;Handayani, et al, 2020). The mechanisms, including down-regulates the expression of MMP9, MMP2, Rac1, and p120; inhibits the gelatin-degradation activity of MMP9 and MMP2, and inhibits cell migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

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Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target

Hastuti

Adisusilo

Ashar

et al. 2022

Indones J Cancer Chemoprevent

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Matrix metalloproteinase-9 (MMP9) has an essential role in cervical cancer metastasis. Sappan wood extract (SWE) from Caesalpinia sappan contains metabolites that have pharmacological effects and can potentially inhibit metastasis by targeting the protein markers. This research aims to discover the potency of compounds in C. sappan as chemopreventive agents for metastasis in cervical cancer by targeting MMP9. SWE was obtained by maceration with methanol and analyzed using thin layer chromatography (TLC). In vitro cytotoxicity test of SWE on HeLa cells was performed by direct counting method. MMP9 expression profiles and survival rates in cervical cancer patients were explored through bioinformatics studies by the GEPIA database. The CMAUP and PubChem databases were used to obtain the metabolomic profile of SWE. SWE compounds’ activities on target proteins were obtained through KNIME software, while its interaction with MMP9 was analyzed using molecular docking with MOE software. We obtained SWE with a yield of 9.7% w/w. The extract contains brazilin and is indicated by the spot appearance at Rf 0.375. The cytotoxicity of SWE against HeLa cells was considered potential as the IC50 value was 54.93 μg/mL. Based on the bioinformatics analysis, there is a significant difference in MMP9 expression between normal and cervical cancer tissue. The patient’s survival probability decreased if MMP9 was overexpressed. The molecular docking results showed that active compounds of SWE bind to the MMP9 inhibition site with higher affinity compared to the native ligand. This study reveals that SWE potential to be developed as a chemopreventive agent through metastasis inhibition in cervical cancer by targeting MMP9.Keywords: Caesalpinia sappan L., metastasis, bioinformatics, molecular docking, MOE.

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Section: Sappan Wood Extraction (Swe) By Maceration Methodsmentioning

confidence: 99%

Section: Sappan Wood Extraction (Swe) By Maceration Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target

Hastuti

Adisusilo

Ashar

et al. 2022

Indones J Cancer Chemoprevent

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“…We confirmed the association of brazilein with the NFκB-HER2 signaling pathway via in silico docking assay. Because the cytotoxic and antimigratory effects of brazilein are nearly identical to those of with brazilin (Handayani et al, 2016(Handayani et al, , 2017(Handayani et al, , 2020Jenie et al, 2018), we tested both compounds in our in silico study. Here, our molecular docking studies focused on Src and PI3K proteins.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synergistic Cytotoxic and Antimigratory Effect of Brazilein and Doxorubicin on HER2-Overexpressing Cells

Handayani

Susidarti

Utomo

et al. 2022

Asian Pac J Cancer Prev

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Objective:The present research aims to report cytotoxic and antimigratory activities of the oxidized form of brazilin, i.e., brazilein, and the effects of the combination of brazilein-doxorubicin on MCF-7/HER2 cells. Methods: The MTT assay was conducted to test the cytotoxic activity, while flow cytometry with PI and PI-annexin V staining were respectively performed for cell cycle and apoptosis analyses. Migration and invasion analyses were assessed via Boyden chamber assay, while HER2, Rac1, p120, MMP2, and MMP9 protein levels were determined by immunoblotting and gelatin zymography. Molecular docking of ligands with HER2, Src, PI3Kα, PI3KΔ, and PI3Kγ proteins was evaluated using MOE 2010. Results: The MTT assay showed that the IC 50 value of brazilein against MCF-7/HER2 cells was 51 ± 2.1 µM. Moreover, brazilein and its combination with doxorubicin-induced G2/M accumulation and apoptosis. Combination of brazilein-doxorubicin inhibited cell migration and tended to decrease HER2, Rac1, p120, MMP2, and MMP9 protein expression levels. Based on our molecular docking study, the docking score of brazilein with PI3Kγ is comparable to that of the native ligand. Conclusion: Taken together, a combination of brazilein-doxorubicin exhibited synergistic cytotoxic and antimigratory effects on MCF-7/HER2 cells.

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“…On the other hand, Caesalpinia sappan (Cs) (family Leguminosae) is traditionally used as a beverage in Indonesia to improve health. This plant has a plain taste and shows several bioactivities including antioxidant, antigenotoxicity, and anticancer (Handayani et al, 2020;Jenie et al, 2017;Meiyanto et al, 2019;Nirmal and Panichayupakaranant, 2015;Rachmady et al, 2016). The flavonoid content in this extract inhibits colon cancer cell growth (Handayani et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Alpha-glucosidase inhibitory activity of the combination of Caesalpinia sappan L. and Garcinia mangostana extract

Artanti¹,

Dewijanti²,

Muzdalifah³

et al. 2023

J App Pharm Sc

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Garcinia mangostana (Gm) and Caesalpinia sappan (Cs) are traditional food used for health supplements. Nevertheless, the synergistic effect of the combinations has never been studied for antidiabetic supplements. This study aimed to evaluate the synergistic α-glucosidase activity of Gm pericarp and Cs heartwood combination extracts. Both plants were extracted with ethanol and water. The total flavonoid content was measured by colorimetric assay. The α-glucosidase inhibitory assay was used to measure the α-glucosidase inhibitory activity of extracts. Synergistic effects were analyzed by calculating the combination index (CI). Targeting compounds inside the extracts were detected using liquid chromatography high-resolution mass spectrometry. Protein-ligand interaction was analyzed using Yet Another Scientific Artificial Reality Application, Protein-Ligand Ant System, and Ligplot + software. The total flavonoid content of Cs aqueous extract was higher than Gm, while the ethanol extract had similar results. The α-glucosidase inhibitory activity of both extracts was in line with their total flavonoid content. The ethanol extracts showed higher activity compared to the aqueous extracts. The combination of both extracts revealed synergistic inhibitory effects on α-glucosidase activity (CI < 1). Flavonoid compounds of Gm and Cs extracts revealed their affinity with the acarbose active site in the α-glucosidase enzyme. Thus, the combination of Gm and Cs extract can be developed as a potential herbal supplement to prevent and manage diabetes mellitus.

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Antimigratory Activity of Brazilin-Containing Fraction from Caesalpinia sappan L. on MDAMB-231 Cells

Cited by 4 publications

References 26 publications

Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target

Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target

Synergistic Cytotoxic and Antimigratory Effect of Brazilein and Doxorubicin on HER2-Overexpressing Cells

Alpha-glucosidase inhibitory activity of the combination of Caesalpinia sappan L. and Garcinia mangostana extract

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