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    Andrographolide targets EGFR to impede epithelial–mesenchymal transition in human breast cancer cells
    (2024-09-15)
    Kaewpiboon, Chutima
    ;
    Boonnak, Nawong
    ;
    Salae, Abdul Wahab
    ;
    Pakdeepromma, Sirichatnach
    ;
    Yawut, Natpaphan
    Despite the primary surgical treatment for breast cancer patients, malignant invasiveness and metastasis remain threatening factors for women with breast cancer. As chemotherapy yields unsatisfactory results, it prompted us to search for effective natural agents with few side-effects. Although andrographolide (ADGL), a natural diterpenoid lactone isolated from Andrographis paniculata, presents anticancer effects, the molecular mechanism remains unknown. Initially, on comparing the expression of proteins related to epithelial–mesenchymal transition (EMT) between nonmetastatic cancer MCF7 cells and highly metastatic cancer MDA-MB-231 cells, we found that MDA-MB-231 cells exhibit higher protein levels of N-cadherin and vimentin and lower protein levels of E-cadherin when compared to MCF7 cells. Moreover, MDA-MB-231 cells also exhibited higher EGFR expression and activity, higher STAT1 activity and abundant HDAC4 expression. To elucidate whether these proteins are closely associated with EMT, EGFR, STAT1 or HDAC4, the proteins were silenced in MDA-MB-231 breast cancer cells by their specific siRNAs. We found that silencing these proteins reduced EMT, indicating an important role of EGFR, STAT1 and HDAC4 in EMT progression. When we treated MDA-MB-231 cells with ADGL as a potential therapeutic drug, we found that ADGL treatment inhibited cell migration and invasion. Furthermore, it also recovered E-cadherin expression and decreased N-cadherin and vimentin protein levels. ADGL treatment reduced EGFR expression at a lower concentration (1 μg/mL); however, STAT1 activity and HDAC4 expression was reduced by a higher concentration (5 μg/mL) of ADGL. Moreover, we observed that the combined treatment with ADGL and siRNAs against these proteins highly sensitized the MDA-MB-231 cells to apoptosis compared to that with ADGL and control siRNA. Collectively, our results suggest that ADGL targets EGFR, thereby inhibiting EMT in human breast cancer cells.
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    Item type:Publication,
    Research Article Biosynthesis of Silver Nanoparticles Using Garcinia cowa Aqueous Leaf Extract and Their Antifungal Activity Against Durian Dieback Pathogen
    (2023-09-01) ;
    Khejonrak, Awadol
    ;
    Kamonpha, Phitsamai
    ;
    Ruangvittayanon, Anuchit
    ;
    Pakdeepromma, Sirichatnach
    Silver nanoparticles (AgNPs) were synthesized under different pH and reaction time using the Garcinia cowa aqueous leaf extract. The formation, crystal structure and morphology of synthesized AgNPs were investigated using UV-Vis spectroscopy, X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. The UV-Vis result indicated that the AgNPs were synthesized using Garcinia cowa aqueous leaf extract at all pH conditions within 10 min. The synthesis of AgNPs was significantly affected by pH condition which was shown by the TEM micrographs. The particle sizes of AgNPs were in a nano-sized range; 6.30 ± 3.52 nm for pH 4, 3.87 ± 2.51 nm for pH 7 and 13.97 ± 11.84 nm for pH 10. Furthermore, the AgNPs prepared in pH 4, pH 7 and pH 10 (120 min reaction time) at different concentrations were assessed for their antifungal activity against durian dieback pathogen. It was found that the 800 mL/L of AgNPs prepared at pH 7, the smallest particle size and good dispersion, showed the highest inhibition mycelial growth at 47.33%, whereas the larger nanoparticles prepared at pH 4 and pH 10 conditions showed lower inhibition of mycelial growth at 43.22% and 32.55%, respectively.
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