In vitro inhibition of 5-α reductase and in vivo suppression of benign prostatic hyperplasia by Physalis angulata ethyl acetate extract.

The inhibitory effect against 5-α reductase of the ethyl acetate (EA) extract from Physalis angulata was evaluated in vitro using mouse prostate homogenates, and the suppression of benign prostatic hyperplasia (BPH) was assessed in a mouse model of testosterone-induced BPH. The EA extract exhibited a potentially inhibitory effect on 5-α reductase with an IC50 of 197 µg/ml. In BPH mice, the EA extract at a dose of 12 mg/kg was comparable to finasteride 5 mg/kg in suppressing BPH in terms of reducing absolute enlarged prostate weight (p < 0.05 vs. BPH group) and mitigating the hypertrophy of glandular elements and prostate connective tissue. Identification of chemical ingredients in the EA extract by UPLC-QTOF-MS revealed 37 substances belonging chiefly to flavonoids and physalins. Further quantification of the EA extract by HPLC-PDA methods revealed that chlorogenic acid, and rutin were the main components. Molecular docking studies of chlorogenic acid and rutin on 5-α reductase showed their high affinity to the enzyme with binding energies of -9.3 and - 9.2 kcal/mol, respectively compared with finasteride (- 10.3 kcal/mol). Additionally, chlorogenic acid inhibited 5-α reductase with an IC50 of 12.07 µM while rutin did not. The presence of chlorogenic acid in the EA extract may explain the inhibitory effects of the EA extract on 5-α reductase, and thus the suppression of BPH.

Anti-Staphylococcus aureus potential of compounds from Ganoderma sp.: A comprehensive molecular docking and simulation approaches.

In this study, a series of secondary metabolites from Ganoderma sp. were screened against Staphylococcus aureus protein targets, including as phosphotransacetylase, clumping factor A, and dihydrofolate reductase, using molecular docking simulations. The chemicals that showed the strongest binding energy with the targeted proteins were ganodermanontriol, lucidumol B, ganoderic acid J, ergosterol, ergosterol peroxide, 7-oxoganoderic acid Z, ganoderic acid AM1, ganosinoside A, ganoderic acid D, and 24R-ergosta-7,2E-diene-3ß,5α,6ß-triol. Interestingly, ganosinoside A showed the greatest affinity for the protein clumping factor A, a result validated by molecular dynamic simulation. Additionally, three natural Ganoderma sp. Strains as Ganoderma lingzhi VNKKK1903, Ganoderma lingzhi VNKK1905A2, and Amauroderma subresinosum VNKKK1904 were collected from Kon Ka Kinh National Park in central land of Vietnam and evaluated for their antibacterial activity against Staphylococcus aureus using an agar well diffusion technique. These results suggest that the fungal extracts and secondary metabolites may serve as valuable sources of antibiotics against Staphylococcus aureus. These findings provided an important scientific groundwork for further exploration of the antibacterial mechanisms of compounds derived from Ganoderma sp. in future research.

Dataset on the compounds from the leaves of Vietnamese Machilus thunbergii and their anti-inflammatory activity.

Machilus thunbergii has a history of traditional applications including treating dyspepsia, apoplexy, headaches, abdominal pain, abdominal distension, and leg edema [1]. It is also employed for alleviating allergies, inflammation, pain relief, promoting blood circulation, addressing costal chondritis, and sinusitis [2]. Research into the chemical composition of M. thunbergii has revealed the presence of lignans, flavonoids, lactones, and essential oils [1,[3], [4], [5]. While some investigations have explored the inhibitory effects of extracts and lignan compounds from this species on NO production [6], [7], [8], there has been no research into the flavonoids isolated from this plant and their potential for inhibiting NO production, given our reachable referencing. The ethyl acetate (EtOAc) soluble fraction of M. thunbergii leaves was subjected to column chromatography (CC) using silica gel and Sephadex LH-20 for compound isolation. Nuclear magnetic resonance (NMR) data primarily facilitated the determination of isolated compound structures. Anti-inflammatory activity was evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Anti-inflammatory activity-guided fractionation led to the isolation of twelve secondary metabolites (1-12). The compounds were identified as quercetin (1), kaempferol (2), rhamnetin (3), quercitrin (4), hyperoside (5), reynoutrin (6), guaijaverin (7), afzelin (8), astragalin (9), rutin (10), kaempferol-3-O-rutinoside (11), and rhamnetin-3-O-rutinoside (12). Compounds 3, 5, 6, 9, 11, and 12 were isolated from M. thunbergii for the first time. Evaluation against LPS-induced NO production in macrophage RAW264.7 cells showed that 1-3 exhibited potent inhibitory activity with IC50 values of 15.45, 25.44, and 19.82 µM, respectively. Compounds 4-9 demonstrated IC50 values ranging from 42.15 to 67.42 µM, while 10-12 exhibited inactivity (IC50 > 100 µM).

Phylogenetic analysis and morphology of Ganoderma multipileum, a Ganoderma species associated with dieback of the metropolitan woody plant Delonix regia (Boj. ex Hook.) Raf. in Vietnam.

Ganoderma multipileum, a wood decay mushroom, was initially discovered and classified in Taiwan through the analysis of its morphology and the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. In this study, we identified a mushroom associated with the dieback of Delonix regia (Boj. ex Hook.) Raf., a woody ornamental street tree in Vietnam, as Ganoderma multipileum. This classification was based on phylogenetic analysis of ITS, RPB2, and TEF1 sequences, as well as morphology assessment and scanning electron microscope observation of basidiospores. The phylogenetic analysis revealed that the specimens collected in Vietnam formed a monophyletic group of Ganoderma multipileum with a high bootstrap value and posterior probability (100%/1.00). Furthermore, the morphological features consistent with laccate Ganoderma, including a thin pileipellis composed of enlarged and bulbous hyphae, and the basidiomes exhibited two different phenotypes. Notably, scanning electron microscopy of the basidiospores revealed ovoid spores with numerous echinules, providing the first documented evidence of this characteristic for Ganoderma multipileum. This research represents the first recorded instance of Ganoderma multipileum in Vietnam associated with the dieback of Delonix regia.

Isolation, structural elucidation, and cytotoxic activity investigation of novel styryl-lactone derivatives from Goniothalamus elegans: in vitro and in silico studies.

Two styryl-lactone derivatives (1 and 2) were isolated from the aerial parts of Goniothalamus elegans. Compound 1 is a newly discovered natural product, and compound 2 is reported in this plant for the first time. The absolute configuration of 1 was determined based on the ECD spectrum. The two styryl-lactone derivatives were tested for cytotoxicity activity against five cancer cell lines and human embryonic kidney cells. The newly discovered compound demonstrated potent cytotoxicity, with IC50 values ranging from 2.05 to 3.96 µM. Computational methods were also applied to investigate the mechanism of the cytotoxic activity of the two compounds. Density functional theory and molecular mechanisms were used to assess the interaction between protein targets to compound 1 and 2, respectively, through the EGF/EGFR signaling pathway. The results indicated that 1 showed a strong binding affinity for two proteins EGFR and HER-2. Finally, ADMET predictions were used to validate the pharmacokinetics and toxicity of these compounds. The results showed that both compounds are likely to be absorbed in the gastrointestinal tract and penetrate the blood-brain barrier. Based on our findings, these compounds may have potential for further studies to be developed into active ingredients for cancer treatment.

Investigating the antibacterial mechanism of Ampelopsis cantoniensis extracts against methicillin-resistant Staphylococcus aureus via in vitro and in silico analysis.

Methicillin-resistant Staphylococcus aureus (MRSA) is a critical pathogen responsible for a wide variety of serious infectious diseases in humans. The accelerated phenomena of drug tolerance, drug resistance, and dysbacteriosis provoked by antibiotic misuse are impeding the effectiveness of contemporary antibiotic therapies primarily used to treat this common worldwide pathogen. In this study, the antibacterial activity of 70% ethanol extract and multiple polar solvents of Ampelopsis cantoniensis were measured against the clinical MRSA isolate. The agar diffusion technique was employed to determine the zone of inhibition (ZOI), accompanied by the use of a microdilution series to identify the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Our results revealed that the ethyl acetate fraction exhibited the most significant antibacterial activity, which was determined to be bacteriostatic based on the MBC/MIC ratio 8. A list of compounds isolated from A. cantoniensis was computationally studied to further investigate the mechanism of action with the bacterial membrane protein PBP2a. The combination of molecular docking and molecular dynamics methods showed that the main compound, dihydromyricetin (DHM), is expected to bind to PBP2a at allosteric site. In addition, DHM was identified as the major compound of ethyl acetate fraction, which accounts for 77.03 ± 2.44% by high performance liquid chromatography (HPLC) analysis. As a concluding remark, our study addressed the antibacterial mechanism and suggested the prioritization of natural products derived from A. cantoniensis as a potential therapy for MRSA.Communicated by Ramaswamy H. Sarma.

Morpho-Anatomical Study And Botanical Identification of Pogostemon auricularius (L.) Hassk. (Lamiaceae).

Pogostemon Desf. includes a wide range of taxa found in subtropical and tropical areas. Few works, however, have studied microanatomical characteristics of Pogostemon species and as yet identified features of Pogostemon auricularius (L.) Hassk. Thus, in this paper, we examined the taxonomic implications of root, stem and leaf morphology for species P. auricularius collected from Quang Tri Province. Light microscopy was mainly used in our study. Qualitative characters like stem quadrangular, hirsute; leaves opposite, ovate, margin serrulate; calyx campanulate; corolla small with separate equal lobes have been found in P. auricularius. Epidermal anatomy on the aerial parts of the species like epidermal cell shape, anticlinal walls, trichomes types, stomata types and calcium oxalate crystals types were examined as well. Quantitative characters like the length and width of leaf blade and inflorescence; the size of oil droplet, stomata and calcium oxalate crystals measured provided taxonomic significance. Based on identifying morphological characteristics of P. auricularius, we aimed to contribute to the taxonomic investigation into the genus Pogostemon and give relative morphological and microanatomical features compared with other taxa.

Role of clinical pharmacists in epilepsy management at a general hospital in Vietnam: a before-and-after study.

BACKGROUND: Clinical pharmacists have an important role in inter-professional healthcare collaboration for epilepsy management. However, the pharmacy practices of managing epilepsy are still limited in Vietnam, deterring pharmacists from routine adjustments of antiepileptic drugs, which could decrease the patients' quality of life. This study aimed to assess the effectiveness of pharmacist interventions in epilepsy treatment at a Vietnamese general hospital. METHODS: A before-and-after study was conducted from January 2016 to December 2018. All patients with a diagnosis of epilepsy and being treated at the investigated hospital were recruited and screened for eligibility and exclusion criteria. The primary outcome was the proportion of patients in good control of their epilepsy (with two seizures or less in a year). The secondary outcome was the number of patients maintaining optimized concentrations within the therapeutic range of carbamazepine (4-12 mg/L), phenytoin (10-20 mg/L), or valproic acid (50-100 mg/L). Collected data were analyzed using two proportions Z-test or Chi-square test. RESULTS: A total of 141 participants were enrolled in the study. While most patients were given lower prescribed daily doses than the recommendations from the World Health Organization, over 56% of the participants still experienced adverse drug effects. More than half of the patients received at least one pharmacists' intervention, which increased by 25.0% the effectiveness of the therapy (p < 0.001) and by 14.6% the number of patients with optimized drug concentrations (p = 0.018). CONCLUSION: Epilepsy management requires a multiple-stepped and comprehensive approach, with a focus on the health and safety of the patients. As part of the healthcare team, pharmacists need to engage at every stage to monitor the patient's response and determine the most effective treatment with the fewest adverse drug reactions. Trial registration ClinicalTrials.gov, NCT04967326. Registered July 19, 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04967326.

Formation of the upper digestive tract by the ileum - right colon for patient with concurrent cancers of the esophagus and the stomach: A case report.

INTRODUCTION AND IMPORTANCE: A very rare case with presence of both esophageal and gastric cancers raised questions on how to perform optimal surgery for such cases. To date, reports on experimental surgery strategies for these rare cases remained sparse in the literatures. CASE PRESENTATION: A 61-year-old male patient having epigastric abdominal pain and swallowing difficulties for a month prior to the hospital. Esophagoscopy and gastroscopy results showed a 2-cm lesion in the esophagus, located around 25 cm away from the teeth arch; and a 2-cm ulcer lesion with high ridge line at the corner of the lesser curvature of stomach. Biopsy results revealed esophageal squamous epithelium carcinoma and poorly differentiated gastric adenocarcinoma. The surgery was esophago-gastrectomy with curettage of the lymph nodes and reconstruction of the upper gastrointestinal tract with the ileum - right colon in the left side of the neck. CLINICAL DISCUSSION: We did not remain the stomach and performed thoracoscopic Ivor Lewis esophagectomy with chest anastomosis, as in previous studies to prevent cancer recurrence. Here, we performed a new surgical method of reconstruct the upper gastrointestinal tract by connecting the upper part of the esophagus at the neck, to the ileum - right colon. CONCLUSIONS: This case could suggest an effective surgical strategy that the ileum - right colon was an organ to be used in replacing the upper gastrointestinal tract in cases of removing the entire stomach and thoracic esophagus, which could serve as a valuable reference for similar rare cases in the future.

On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 µM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 µM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure-activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

PTP1B and α-glucosidase inhibitors from Selaginella rolandi-principis and their glucose uptake stimulation.

As part of an ongoing search for new protein tyrosine phosphatase 1B inhibitors and glucose uptake stimulators from nature, a new coumarin, selaginolide A (1) and four known isoflavones (2‒5) were isolated from the ethanol extract of a Vietnamese medicinal plant Selaginella rolandi-principis. The chemical structures of the isolates were elucidated by extensive analysis of spectroscopic and physicochemical data. Compounds 3‒5 have been identified from Selaginella genus for the first time. The antidiabetic properties of the isolates (1‒5) were investigated using in vitro assay on 2-NBDG uptake in 3T3-L1 adipocytes and against PTP1B and α-glucosidase enzyme activities as well. Compounds 1 exhibited the most potency with inhibitory IC50 values of 7.40 ± 0.28 and 7.52 ± 0.37 µM against PTP1B and α-glucosidase, respectively. Compounds 3 and 5 possessed potential inhibitions on PTP1B enzyme with IC50 values of 23.02 ± 1.29 and 11.08 ± 0.92 µM and moderate inhibitions on α-glucosidase with IC50 values of 36.47 ± 1.87 and 55.73 ± 2.58 µM, respectively. Compounds 2 and 4 showed weak PTP1B inhibitory activity (IC50 > 30 µM) but displayed remarkable α-glucosidase inhibition with IC50 values of 3.39 ± 0.87 and 9.72 ± 0.62 µM, respectively. Furthermore, ursolic acid as a positive control (IC50 3.42 ± 0.26 µM) and compounds 1 and 5 acted as mixed-competitive inhibitors against PTP1B enzyme with Ki values of 6.46, 10.28, and 15.01 µM, respectively. In addition, compounds 1 and 5 also showed potent stimulatory effects on 2-NBDG uptake at a concentration of 10 µM. The obtained result might suggest the potential of new coumarin (1) as a new type of natural PTP1B and α-glucosidase inhibitor for further research and development of antidiabetic and obese agents.Graphic abstract.

Anti-inflammatory xanthone derivatives from Garcinia delpyana.

Two new xanthones delpyxanthone A (1) and delpyxanthone B (3), together with four known ones, gerontoxanthone I (2), α-mangostin (4), cowanin (5) and cowanol (6) were isolated from the stem bark of Garcinia delpyana. The chemical structures of 1-6 were established mainly using nuclear magnetic resonance (NMR) and mass spectrometry (MS). The anti-inflammatory activity of the isolated compounds was evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells in vitro. Compounds 1-4 showed significant inhibitory activity against the LPS-induced NO production in RAW264.7 cells with IC50 values ranging from 14.5 to 28.2 µM, but the others were inactive. The results suggested that G. delpyana and its constituents might be potential anti-inflammatory agents on RAW 264.7 cells.[Formula: see text].

Bioactive compounds from Physalis angulata and their anti-inflammatory and cytotoxic activities.

A new compound, physalucoside A (1), together with seven withanolides (2-8) and three flavonoids (9-11), were isolated from Physalis angulata L. (Solanaceae), a medicinal plant native to Vietnam. The chemical structures of these compounds were elucidated by one- and two-dimensional NMR spectra, high-resolution electrospray ionization mass spectrometry analyses, and chemical reactivity. The anti-inflammatory and cytotoxic activities of isolated compounds were also evaluated. These data suggest that the anti-inflammatory activity of P. angulata is due primarily to its withanolide content. This study demonstrates the potential of withanolides as promising candidates for the development of new anti-inflammatory drugs.

Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.

Antioxidant and Cell Proliferation Properties of the Vietnamese Traditional Medicinal Plant Peltophorum pterocarpum.

Peltophorum pterocarpum is regarded as one of the most important medicinal plants in the traditional medicine system of Vietnam. However, scientific evidence for the antioxidant effects against lipid peroxidation and the potential effects in cancer of this plant are lacking. In our experiments, 70% ethanolic extracts of P. pterocarpum leaves (LPP) and stem bark (SPP) were evaluated for their low-density lipoprotein (LDL) oxidation and cytotoxic activity against cancer cell lines. Both LPP and SPP inhibited Cu2+-mediated LDL by increasing the lag time of conjugated diene formation and inhibiting the generation of thiobarbituric acid reactive substances (TBARS) in a dose-dependent manner. In cancer cells, LPP and SPP triggered the most potent cytotoxic effects against human leukemia cells, CRF-SBA and HL-60, with half-maximal inhibitory concentration (IC50) values ranging from 118.5 to 157.2 µg/mL. SPP exhibited significant cytotoxicity against MIA PACA2, A549, and KG cell lines with IC50 values of 167.5, 244.1 and 255.0 µg/mL, respectively. Meanwhile, LPP showed cytotoxic activity against KG with an IC50 value of 228.1 µg/mL. SPP mediated cytotoxicity in HL-60 and CCRF-SBA cells through the activation of the apoptosis pathway, including the activation of caspases 3, and 9 and poly (ADP-ribose) polymerase (PARP). These results suggested that SPP may prevent the development and progression of atherosclerosis and leukemia in humans.

Cassaine Diterpenoid Amide from Stem Bark of Erythrophleum fordii Suppresses Cytotoxic and Induces Apoptosis of Human Leukemia Cells.

Cassaine diterpenoids amides from the stem bark of Vietnamese Erythrophleum fordii Oliver were screened for their cytotoxic activity against human cancer cells. The cell proliferation assay results showed that, among the active compounds, 3ß-acetyl-nor-erythrophlamide (3AEP) exhibited the most potential cytotoxicity against human leukemia HL-60 and KG cells with IC50 values of 12.0 ± 1.2 and 18.1 ± 2.7 µM, respectively. Treatment of 3AEP resulted in the apoptosis of HL-60 cells via the activation of caspase 3, and poly (ADP-ribose) polymerase (PARP). Molecular docking in silico results showed that the 3AEP can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.51 and -9.63 kcal/mol respectively. These results indicated that the stem bark of Vietnamese E. fordii and its cassaine diterpenoid amides may be useful in the apoptosis induction of human leukemia cancer cells.

Glucose Uptake Stimulatory and PTP1B Inhibitory Activities of Pimarane Diterpenes from Orthosiphon stamineus Benth.

Seven pimarane diterpenes (1-7) were isolated from Orthosiphon stamineus Benth. by assay-guided isolation. All of the isolates possessed a 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose uptake effect in 3T3-L1 adipocytes at concentrations of 5 and 10 µM. Most of them showed potent inhibition against protein tyrosine phosphatase 1B with IC50 values ranging from 0.33 to 9.84 µM. In the kinetic study, all inhibition types were exposed for the examined potencies, including mixed-competitive (1), non-competitives (3 and 5), competitive (6), and uncompetitive (7). The results suggested that O. stamineus and its pimarane diterpenes might exert the hypoglycemic effect via the insulin signaling pathway targeting inhibition of protein tyrosine phosphatase 1B (PTP1B) activity.

Chemical Composition and Biological Activities of Metabolites from the Marine Fungi Penicillium sp. Isolated from Sediments of Co To Island, Vietnam.

Marine microorganisms are an invaluable source of novel active secondary metabolites possessing various biological activities. In this study, the extraction and isolation of the marine sediment Penicillium species collected in Vietnam yielded ten secondary metabolites, including sporogen AO-1 (1), 3-indolecarbaldehyde (2), 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3), 2-[(2R-hydroxypropanoyl)amino]benzamide (4), 4-hydroxybenzandehyde (5), chrysogine (6), 3-acetyl-4-hydroxycinnoline (7), acid 1H-indole-3-acetic (8), cyclo (Tyr-Trp) (9), and 2',3'-dihydrosorbicillin (10). Their structures were identified by the analysis of 1D and 2D NMR data. Among the isolated compounds, 2-[(5-methyl-1,4-dioxan-2-yl)methoxy]ethanol (3) showed a strong inhibitory effect against Enterococcus faecalis with a minimum inhibitory concentration value of 32 µg/mL. Both 2-[(2R-hydroxypropanoyl)amino]benzamide (4) and 4-hydroxybenzandehyde (5) selectively inhibited E. coli with minimum inhibitory concentration values of 16 and 8 µg/mL, respectively. 2',3'-Dihydrosorbicillin (10) potentially inhibited α-glucosidase activity at a concentration of 2.0 mM (66.31%).

The Effects of 2',4'-Dihydroxy-6'-methoxy-3',5'- dimethylchalcone from Cleistocalyx operculatus Buds on Human Pancreatic Cancer Cell Lines.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a principal natural chalcone of Cleistocalyx operculatus buds, suppresses the growth of many types of cancer cells. However, the effects of this compound on pancreatic cancer cells have not been evaluated. In our experiments, we explored the effects of this chalcone on two human pancreatic cancer cell lines. A cell proliferation assay revealed that DMC exhibited concentration-dependent cytotoxicity against PANC-1 and MIA PACA2 cells, with IC50 values of 10.5 ± 0.8 and 12.2 ± 0.9 µM, respectively. Treatment of DMC led to the apoptosis of PANC-1 by caspase-3 activation as revealed by annexin-V/propidium iodide double-staining. Western blotting indicated that DMC induced proteolytic activation of caspase-3 and -9, degradation of caspase-3 substrate proteins (including poly[ADP-ribose] polymerase [PARP]), augmented bak protein level, while attenuating the expression of bcl-2 in PANC-1 cells. Taken together, our results provide experimental evidence to support that DMC may serve as a useful chemotherapeutic agent for control of human pancreatic cancer cells.