The development of cancer at an advanced stage is signed with metastasis that trigger the high of mortality caused breast cancer, possitive HER2 type mainly. Boesenbergia pandurata known as medicinal plant possessing anticancer potential due to the cytototoxic and antimetastatic characteristic of its active compound. The aim of this study is to observe the inhibitory of migration of Boesenbergia pandurata ethanolic extract (BPEE) in combination with doxorubicin (Dox) on MCF-7/HER2 cells. BPEE was prepared by 96% ethanol maceration. Under MTT assay, BPEE decreased the cells viability with IC50 value of 23 ± 3.9 μg/mL. Lamellipodia and wound healing assay analysis showed that BPEE (5 μg/mL) and its combination with doxorubicin (10 nM) inhibited cells migration after 48 hours observation, while gelatin zymography analysis showed that this combination did not affect the expression of MMP2 and MMP9 proteins, but single treatment of BPEE was more able to decrease the expression of both MMP. The combination with those concentrations inhibited the cells migration but not with the cells viability. Thus, BPEE is potential to be developed as antimetastatic agent. The mechanism itself needs to be explored further.
Fingerroot (Boesenbergia pandurata) is an Indonesian herb, with anti-proliferation and anti-migratory effects against several cancer cells. This study aims to investigate the anticancer property of Fingerroot Extract (FE) in combination with doxorubicin (Dox) against 4T1, a metastatic breast cancer cell lines. FE was prepared by 96% ethanol maceration and characterized by thin-layer chromatography analysis. FE was subjected to a cytotoxicity test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay alone or in combination with 10 nM Dox against 4T1 cells. Cytotoxic effect was then confirmed by measure reactive oxygen species (ROS) intracellular level using 2’,7’-dichloroflourescin diacetate (DCFDA)-staining flow cytometry-based assay. The anti-migratory effect was observed using scratch wound healing assay and gelatin zymography to investigate matrix metalloproteinase (MMP)-9 expression. FE showed a cytotoxic effect with an inhibitory concentration 50 (IC50) value of 25.5±3.9 μg/mL and performed an improved effect in combination with 10 nM Dox. A single treatment of FE decreased ROS intracellular level, while in combination with Dox, FE increased the ROS intracellular level. Further, at 42 h observation, FE and its combination with Dox inhibited the migration of 4T1 cells with % closure of 82.6 and 82.5, respectively, correlates with a significant decrease of MMP-9 expression. Overall, FE performs a cytotoxic activity and anti-migration activity on 4T1 breast cancer cells.Keywords: Boesenbergia pandurata, cytotoxic, ROS, anti-migration, 4T1
Antioxidants have the ability to scavenge free radicals, leading to inhibition of cells senescence. Secang Heartwood (Caesalpinia sappan L.) contains flavonoid brazilein, known of its high antioxidant activity. However, the activity of secang as senescent cells inhibitor has not been known. The aim of this study is to explore the potential of Caesalpinia sappan ethanolic extract (CSE) as free radical scavenger, thus inhibits senescent cells. Two concentrations of SE under IC50, 2µg/mL, 5µg/mL and 10µg/mL were applied on Mesenchymal Stem Cells (MSCs) and combined with 5µM of doxorubicin (Dox) as senescence inductor; both of them were compared with MSCs-Dox group. X-gal, chromogenic substrate of senescent cells, was given on MSCs, giving blue stain on senescent cells. To explore brazilein mechanism in senescence inhibition, molecular docking using PLANTS on topoisomerase II was performed. MSCs that treated with 10µg/mL of SE qualitatively showed reduction intensity of blue stain. Number of stained cells also reduced from 76% of MSCs-Dox to 38 % of 10µg/mL SE-Dox group. Docking score shows that brazilein (-86.91) is more stable to interact with topoisomerase II than doxorubicin (-82.46) and has same binding site (Val 174). These findings demonstrate starting knowledge on CSE potential as senescent cells inhibitor through brazilein activity on topoisomerase II.Keyword: Caesalpinia sappan L., Senescence, β-galactosidase, Molecular Docking
Cyclophosphamide (CPA) is an effective chemotherapeutic agent, but has side effect, causing DNA damage (genotoxic). Papaya leaf (Carica papaya L.) is known has flavonoid compound, quercetin. Quercetin is known has DNA protecting effect (antigenotoxic effect) by metabolism modulation. Thus, the aim of this research is to investigate the antigenotoxic effect of ethanolic extract of papaya (Carica papaya L.) leaf (EEPL) on CPA induced mice. The antigenotoxic effect was evaluated by mammalian in vivo micronucleus test. EEPL was orally administered as single treatment at dose 1000 mg/kgBW and in combination with CPA 50 mg/kgBW at dose 250 mg/kgBW; 500 mg/kgBW; and 1000 mg/kgBW. Molecular docking using PLANTS on CYP3A4 was performed to explore the antigenotoxic effect mechanism. The three different combination dose of EEPL with CPA significantly (p<0.05) decreased the amount of micronucleated polychromatic erytrhocyte (MNPCE)/1000 polychromatic erythrocyte (PCE) and also increased % PCE/(PCE+normochromatic erythrocyte (NCE), compared with single dose of CPA. Nevertheless, the antigenotoxic effect wasn't significant compared with each combination dose. The docking score result showed quercetin (-82,41) has more potent interaction to CYP3A4 than cyclophosphamide (-70,16) and both of them has similar active site at amino acid residue Ile 369 and Thr 309. The results obtained indicated that EEPL at dose 250 mg/KgBB is the optimal dose as antigenotoxic agent by interaction between quercetin with CYP3A4 based on molecular docking.
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