1.Targeting YAP-TEAD Interaction with Honokiol to Inhibit Melanoma Progression and Metastasis
Chaelin LEE ; Hien Thi Thu DO ; Xiang FEI ; Sanha LEE ; Soonsil HYUN ; Seung-Yong SEO ; Inmoo RHEE
Biomolecules & Therapeutics 2026;34(1):154-164
The Hippo-YAP/TEAD pathway plays a central role in melanoma progression by regulating tumor cell proliferation, survival, and migration. Using a NanoLuc Binary Technology (NanoBiT) protein-protein interaction assay, we screened honokiol-based small molecules and identified several analogues that disrupt the YAP-TEAD interaction. HK03 was the most effective analogue, leading to a pronounced reduction in Cyr61 levels and diminished Erk and Akt phosphorylation in B16-F10 melanoma cells. HK03 also blocked epithelial–mesenchymal transition (EMT) and impaired melanoma cell migration in wound-healing assays. In vivo, HK03 treatment markedly reduced metastatic burden in a B16-F10 lung metastasis model. These findings suggest that honokiol derivatives, particularly HK03, represent potential lead compounds for targeting the YAP-TEAD axis in melanoma therapy.
2.Anti-Inflammatory and Immunoregulatory Activities In Vitro of Coumarins Isolated from the Twigs and Leaves of Wikstroemia indica (L.) C.A. Mey.
Van Lieu NGUYEN ; Van Anh CAO ; Thi Thu NGUYEN ; Thi Hien TRAN ; Viet Dung HOANG ; Thi Ha DO
Natural Product Sciences 2025;31(4):284-290
Six coumarins were isolated from two bioactive fractions of the 70% ethanol extract from the twigsand leaves of Wikstroemia indica (L.) C.A. Mey. (Thymelaeaceae), namely the ethyl acetate fraction (WIE) and the water fraction (WIW). These compounds were identified as umbelliferone (1), daphnoretin (2), daphnorin (3), adicardin (4), wikstronutin (5), and triumbelletin-7-O-β-D-glucoside (6). Compound 4 is reported for the first time in the genus Wikstroemia, whereas compound 5 is newly identified in this species. All six compounds were evaluated for their effects on Interleukin-1 beta (IL-1β) and IL-10 secretion in Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, among which compounds 1, 2, 5, and 6 showed stronger activity. These four coumarin derivatives further suppressed the production of Foxp3, Interferon-alpha (IFN-α), IFN-γ, and IL-17 in LPSstimulated CD4+ T cells. The IC50 values ranged from 18.84 ± 1.16 to 43.45 ± 5.34 μM for Foxp3, 8.96 ± 1.45 to 22.42 ± 4.12 μM for IFN-α, 9.28 ± 1.23 to 16.83 ± 2.15 μM for IFN-γ, and 12.62 ± 2.57 to 22.92 ± 4.41 μM for IL-17. Notably, compound 6 exhibited the strongest immunomodulatory effect. Overall, the findings suggest that coumarins from W. indica possess promising immunomodulatory and anti-inflammatory potential.
3.Alkaloids with Acetylcholinesterase Inhibitory Activities from Crinum latifolium L.
Vu Thi TRANG ; Pham Van CONG ; Nguyen Van DAN ; Nguyen Thi Thu HIEN ; Do Thanh TUAN ; Le Tuan ANH ; Hoang Dac THANG ; Ngo Viet DUC ; Hoang Le Tuan ANH
Natural Product Sciences 2024;30(4):304-308
A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).
4.Alkaloids with Acetylcholinesterase Inhibitory Activities from Crinum latifolium L.
Vu Thi TRANG ; Pham Van CONG ; Nguyen Van DAN ; Nguyen Thi Thu HIEN ; Do Thanh TUAN ; Le Tuan ANH ; Hoang Dac THANG ; Ngo Viet DUC ; Hoang Le Tuan ANH
Natural Product Sciences 2024;30(4):304-308
A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).
5.Alkaloids with Acetylcholinesterase Inhibitory Activities from Crinum latifolium L.
Vu Thi TRANG ; Pham Van CONG ; Nguyen Van DAN ; Nguyen Thi Thu HIEN ; Do Thanh TUAN ; Le Tuan ANH ; Hoang Dac THANG ; Ngo Viet DUC ; Hoang Le Tuan ANH
Natural Product Sciences 2024;30(4):304-308
A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).
6.Effects of Coumarins from Roots of Paramignya scandens (Griff.) Craib on LPS-induced IL-1β and IL-10 Cytokine Production in RAW 264.7 Macrophages
Tra My NGUYEN ; Thi Ha DO ; Thi Thu NGUYEN ; Thi Diep VU ; Thi Hien TRAN ; Hoang Tuan NGUYEN ; Thi Phuong DOAN ; Won Keun OH ; Jeong Hill PARK
Natural Product Sciences 2024;30(1):30-38
Based on our previous study, we evaluated the modulatory effects on LPS-induced IL-1β and IL-10 cytokine production in RAW 264.7 macrophages of several medicinal herbs, including P. scandens. The results showed that P. scandens extract showed significant effects on LPS-induced IL-1β and IL-10 cytokine production in RAW 264.7 macrophages. Therefore, in the current research, we focused on the P. scandens sample. Cytokine production effects bioassay-guided isolation of ethyl acetate fraction of 70% ethanol extract from roots of Paramignya scandens (XL) obtained seven coumarins (1–7). Their chemical structures were identified using spectroscopic methods (NMR and MS) and compared with those previously published data to be xanthyletin (1), luvangetin (2), clausenidin (3), nordentatin (4), dentatin (5), clausarin (6), and anisocoumarin E (7). This study represents the first report on the presence of compounds 3, 6, and 7 in the Paramignya genus and compounds 1 and 2 in XL. All isolates (1–7) exhibited significant inhibition of LPS-induced interleukin (IL)-1β production compared to the LPS 5 ng/mL control group, with IL-1β concentrations ranging from 42.77 to 69.76 pg/mL. Additionally, the IL-10 production induced by compounds 1‒7 in LPS-stimulated RAW 264.7 macrophages ranged from 175.98 to 321.56 pg/mL, demonstrating a marked increase as compared to the LPS 5 ng/mL control group. The stimulatory effect on IL-10 production and inhibitory effect on IL-1β production of compounds 1, 2, and 6 gradually increased with the test concentration in both RAW 264.7 macrophages and LPS-induced RAW 264.7 macrophages. Compounds 1, 2, and 6 inhibited IL-1β production in LPS-induced RAW 264.7 macrophages with IC 50 values of 10.70 ± 1.18 µM, 8.57 ± 1.05 µM, and 17.43 ± 1.05 µM, respectively. These findings highlight the potential of all the compounds derived from P. scandens roots in inducing IL-1β and IL-10 cytokines activity in LPS-stimulated RAW 264.7 macrophages. The results contributed to expanding the knowledge of the chemistry and bioactivities of P. scandens and provided valuable data for future investigations on this species.
7.Alkaloids with Acetylcholinesterase Inhibitory Activities from Crinum latifolium L.
Vu Thi TRANG ; Pham Van CONG ; Nguyen Van DAN ; Nguyen Thi Thu HIEN ; Do Thanh TUAN ; Le Tuan ANH ; Hoang Dac THANG ; Ngo Viet DUC ; Hoang Le Tuan ANH
Natural Product Sciences 2024;30(4):304-308
A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).
8.Active case finding to detect symptomatic and subclinical pulmonary tuberculosis disease: implementation of computer-aided detection for chest radiography in Viet Nam
Anh L Innes ; Andres Martinez ; Gia Linh Hoang ; Thi Bich Phuong Nguyen ; Viet Hien Vu ; Tuan Ho Thanh Luu ; Thi Thu Trang Le ; Victoria Lebrun ; Van Chinh Trieu ; Nghi Do Bao Tran ; Nhi Dinh ; Huy Minh Pham ; Van Luong Dinh ; Binh Hoa Nguyen ; Thi Thanh Huyen Truong ; Van Cu Nguyen ; Viet Nhung Nguyen ; Thu Hien Mai
Western Pacific Surveillance and Response 2024;15(4):14-25
Objective: In Viet Nam, tuberculosis (TB) prevalence surveys revealed that approximately 98% of individuals with pulmonary TB have TB-presumptive abnormalities on chest radiographs, while 32% have no TB symptoms. This prompted the adoption of the “Double X” strategy, which combines chest radiographs and computer-aided detection with GeneXpert testing to screen for and diagnose TB among vulnerable populations. The aim of this study was to describe demographic, clinical and radiographic characteristics of symptomatic and asymptomatic Double X participants and to assess multilabel radiographic abnormalities on chest radiographs, interpreted by computer-aided detection software, as a possible tool for detecting TB-presumptive abnormalities, particularly for subclinical TB.
Methods: Double X participants with TB-presumptive chest radiographs and/or TB symptoms and known risks were referred for confirmatory GeneXpert testing. The demographic and clinical characteristics of all Double X participants and the subset with confirmed TB were summarized. Univariate and multivariable logistic regression modelling was used to evaluate associations between participant characteristics and subclinical TB and between computer-aided detection multilabel radiographic abnormalities and TB.
Results: From 2020 to 2022, 96 631 participants received chest radiographs, with 67 881 (70.2%) reporting no TB symptoms. Among 1144 individuals with Xpert-confirmed TB, 51.0% were subclinical. Subclinical TB prevalence was higher in older age groups, non-smokers, those previously treated for TB and the northern region. Among 11 computer-aided detection multilabel radiographic abnormalities, fibrosis was associated with higher odds of subclinical TB.
Discussion: In Viet Nam, Double X community case finding detected pulmonary TB, including subclinical TB. Computer-aided detection software may have the potential to identify subclinical TB on chest radiographs by classifying multilabel radiographic abnormalities, but further research is needed.
9.Alkaloids with Acetylcholinesterase Inhibitory Activities from Crinum latifolium L.
Vu Thi TRANG ; Pham Van CONG ; Nguyen Van DAN ; Nguyen Thi Thu HIEN ; Do Thanh TUAN ; Le Tuan ANH ; Hoang Dac THANG ; Ngo Viet DUC ; Hoang Le Tuan ANH
Natural Product Sciences 2024;30(4):304-308
A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).
10.Complement Regulatory Protein CD46 Manifests a Unique Role in Promoting the Migration of Bladder Cancer Cells
Thuy Thi NGUYEN ; Hien Duong THANH ; Manh-Hung DO ; Chaeyong JUNG
Chonnam Medical Journal 2023;59(3):160-166
CD46 is a membrane-bound complement regulatory protein (mCRP) possessing a regulatory role with the complement system. CD46 protects the host cells from damage by complement. Expression of CD46 is also highly maintained in many cancers, including bladder cancers, and thus functions as a receptor for many cancer therapeutic viruses.In this study we report a unique role of CD46 as a progression factor of cancer cells in bladder cancers. Resulting data from a DNA microarray using CD46-altered HT1376 bladder cancers demonstrated a pool of target genes, including complement C3 chain (C3), matrix Gla protein (MGP), AFAP-AS1, follicular dendritic cell secreted protein (FDCSP), MAM domain containing 2 (MAMDC2), gamma-aminobutyric acid A receptor pi (GABRP), transforming growth factor, beta-induced (TGFBI), a family of cytochrome P450 (CYP24A1), sialic acid binding Ig-like lectin 6 (SIGLEC6), metallothionein 1E (MT1E), and several members of cytokeratins. Subsequent studies using quantitative RT-PCR and Western blot analyses confirmed CD46-mediated regulation of C3, MGP, and keratin 13 (KRT13). MGP and KRT13 are known to be involved in cell migration and cancer cell metastasis. A cell migration assay demonstrated that CD46 enhanced migratory potential of bladder cancer cells. Taken all together, this report demonstrated that CD46 is generally overexpressed in bladder cancers and plays a unique role in the promotion of cancer cell migration. Further detailed studies are needed to be performed to clarify the action mechanism of CD46 and its application to cancer therapeutics.


Result Analysis
Print
Save
E-mail