Nitwara Wikan

Background: Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related mortality. Current therapies are limited by drug resistance and adverse effects, highlighting the need for new strategies. Panduratin A (PA), a chalcone from Boesenbergia rotunda, has reported anticancer activity. This study investigated the effects of PA in NSCLC cells and whether PA enhances tumor necrosis factor alpha (TNF-α)-associated cell death. Methods: Human NSCLC cell lines A549 and H1299 were treated with PA alone or in combination with TNF-α. Cytotoxicity and apoptosis were assessed using cell-viability assays, cell-number analysis, and flow cytometry. Western blotting was used to evaluate caspase-3 activation and PARP-1 cleavage. Cell-cycle distribution was analyzed to determine the impact of PA on cell-cycle progression. Results: PA reduced cell number and induced cell death in both A549 and H1299 cells, and co-treatment with TNF-α increased apoptosis compared with single-agent treatment. PA increased the G1-phase fraction and, in a concentration-dependent manner, reduced expression of thymidine kinase and cyclin A2, consistent with a G1-associated arrest phenotype. Combination treatment also increased the sub-G1 population. Conclusions: PA promotes apoptosis in NSCLC cells and enhances TNF-α-associated apoptotic cell death in vitro, accompanied by a G1-associated cell-cycle phenotype. These findings provide an in vitro framework for studying natural compounds as modulators of TNF-α-driven apoptosis and support further mechanistic validation in more disease-relevant models.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases and frequently associated with poor outcomes due to resistance to conventional therapies. The epidermal growth factor (EGF)–epidermal growth factor receptor (EGFR) axis plays a central role in NSCLC progression by activating downstream phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling, thereby promoting survival and proliferation. Natural compounds have emerged as promising modulators of these pathways, and oxyresveratrol (OXY), a hydroxylated analog of resveratrol, has been reported to possess antioxidant and anticancer properties, though its mechanistic role in NSCLC remains unclear. In this study, we investigated the effects of OXY in EGF-stimulated A549 and H1299 cells. OXY significantly reduced metabolic activity and decreased cell number in a dose-dependent manner and increased the proportion of apoptotic cells. Mechanistically, OXY selectively attenuated EGF-induced AKT phosphorylation while largely sparing extracellular signal–regulated kinase 1/2 (ERK1/2) activation and did not measurably alter EGFR phosphorylation or receptor trafficking dynamics. These findings indicate that OXY exposure is associated with AKT-selective signaling suppression and reduced cellular fitness in NSCLC cells, without evidence of direct EGFR inhibition. Further genetic rescue and pathway-epistasis studies are required to establish causal dependency on AKT signaling and to support in vivo validation.

Background/Objectives: Pinostrobin is a natural flavonoid compound, a specific type of monohydroxyflavanone, found in various plants like fingerroot and honey. It displays various biological activities such as antioxidant, antimicrobial, anti-adaptogenic and anti-inflammatory. However, the anti-inflammatory effect on human macrophages has not yet been investigated. Methods: In this study, we reported the effect of pinostrobin on inhibiting production of pro-inflammatory cytokines and chemokines in human THP-1 macrophages exposed to lipopolysaccharide. In addition, the responsible mechanisms of pinostrobin at the molecular level were identified. Results: Results from ELISA demonstrated that pinostrobin significantly inhibited production of pro-inflammatory cytokines and chemokines, including IL-6, TNF-α, IL-8, MCP-1/CCL2, and CXCL10/IP10. In addition, data from Western blot analysis revealed that pinostrobin suppressed LPS-induced NF-κB activation, in part through blocking IκB-α phosphorylation and degradation as well as NF-κB phosphorylation and nuclear translocation. Results from immunofluorescence study verified that pinostrobin effectively inhibited IκB-α degradation and NF-κB nuclear translocation. Additionally, pre-treatment of pinostrobin alone retained the existence of IκB-α in the cytoplasm of human macrophages, and this may contribute to the enhanced inhibitory activity of pinostrobin in suppressing NF-κB activation. Conclusions: This study provided accumulated evidence that pinostrobin exhibits anti-inflammatory activities, and these properties of pinostrobin in human macrophages stem from the inhibition of the NF-κB signal transduction pathway. Our findings suggest that pinostrobin may be useful for the development of therapeutic treatment of inflammation-related diseases or conditions in which NF-κB is overactive.

Upon exposure to inflammatory stimuli including TNF-α, endothelial cells are activated leading to the adhesion of monocytes to their surface. These events are involved in the pathophysiology of atherosclerosis. Since TNF-α activates the NF-κB pathway, which contributes to atherosclerosis, targeting this signaling pathway may help prevent the risk of developing the disease. The current study elucidated the inhibitory effect of panduratin A (PA) on TNF-α-induced endothelial activation and monocyte adhesion. We discovered that PA reduced the level of pro-inflammatory cytokine IL-6 and chemokine MCP-1 in the media collected from endothelial cells stimulated with TNF-α. In addition, PA inhibited the expression of ICAM-1 and VCAM-1 on the surface of TNF-α-induced endothelial cells resulting in a decrease in the number of monocytes attached to endothelial cell surface. Mechanistically, PA prevented IκB degradation and specifically suppressed NF-κB phosphorylation and nuclear translocation in endothelial cells. However, PA had no inhibitory effect on the phosphorylation of AKT, ERK1/2, p38, and JNK. Taken together, PA blocked the production of cytokine and chemokine, adhesion molecules, and monocyte adhesion in response to TNF-α stimulation, in part, through NF-κB inhibition. Our study suggests that PA may possibly be effective in blocking the pathophysiology of atherosclerosis.

Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin’s ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY’s potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.

Vulvovaginal candidiasis (VVC) is the most common cause of vaginal discharge among women. The present study aimed to investigate the synergistic anticandidal effect of lactobacillus cultures supplemented with plant extracts. Among 600 isolates of lactic acid bacteria, 41 isolates exhibited inhibitory activity against Candida albicans ATCC10231. Six out of 41 cell-free supernatants demonstrated the most potent antibacterial and anticandidal activities. They also inhibited the clinical isolates of C. albicans, causing VVC and non-C. albicans. The synergistic effect between Lactobacillus crispatus 84/7 and Limosilactobacillus reuteri 89/4 was demonstrated by the lowest fractional inhibitory concentration index (FICI = 0.5). The synbiotic culture of bacterial combination, cultured with Jerusalem artichoke (H. tuberosus) extract, also exhibited the strongest inhibition against the tested C. albicans. Biofilm formation decreased after 12 h of incubation in the selected cell-free supernatants of this synbiotic culture. The anticandidal activity of crude extracts was lost after treatment with proteinase K and trypsin but not with heating conditions, suggesting that it may be a heat-stable substance. In conclusion, the combination of L. crispatus 84/7 and L. reuteri 89/4 with H. tuberosus may be a promising candidate for inhibiting Candida infection and biofilm formation, with the potential use as ingredients in vaginal biotherapeutic products.

Re-epithelialization is delayed in aged skin due to a slow rate of keratinocyte proliferation, and this may cause complications. Thus, there has been development of new therapies that increase treatment efficacy for skin wounds. Epidermal growth factor (EGF) has been clinically used, but this agent is expensive, and its activity is less stable. Therefore, a stable compound possessing EGF-like properties may be an effective therapy, especially when combined with EGF. The current study discovered that pinocembrin (PC) effectively synergized with EGF in increasing keratinocyte viability. The combination of PC and EGF significantly enhanced the proliferation and wound closure rate of the keratinocyte monolayer through activating the phosphorylation of ERK and Akt. Although these effects of PC were like those of EGF, we clearly proved that PC did not transactivate EGFR. Recent data from a previous study revealed that PC activates G-protein-coupled receptor 120 which further activates ERK1/2 and Akt phosphorylation. Therefore, this clearly indicates that PC possesses a unique property to stimulate the growth and survival of keratinocytes through activating a different receptor, which subsequently conveys the signal to cross-talk with the effector kinases downstream of the EGFR, suggesting that PC is a potential compound to be combined with EGF.

In the current study, we identified a mechanism of resveratrol (RES) underlying its anti-cancer properties against human ovarian adenocarcinoma SKOV-3 cells. We investigated its anti-proliferative and apoptosis-inducing effects in combination with cisplatin, using cell viability assay, flow cytometry, immunofluorescence study and Western blot analysis. We discovered that RES suppressed cancer cell proliferation and stimulated apoptosis, especially when combined with cisplatin. This compound also inhibited SKOV-3 cell survival, which may partly be due to its potential to inhibit protein kinase B (AKT) phosphorylation and induce the S-phase cell cycle arrest. RES in combination with cisplatin strongly induced cancer cell apoptosis through activating the caspase-dependent cascade, which was associated with its ability to stimulate nuclear phosphorylation of p38 mitogen-activated protein kinase (MAPK), well recognized to be involved in transducing environmental stress signals. RES-induced p38 phosphorylation was very specific, and the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) was not mainly affected. Taken together, our study provides accumulated evidence that RES represses proliferation and promotes apoptosis in SKOV-3 ovarian cancer cells through activating the p38 MAPK pathway. It is interesting that this active compound may be used as an effective agent to sensitize ovarian cancer to apoptosis induced by standard chemotherapies.

Background: Zika virus (ZIKV) is a mosquito transmitted virus spread primarily byAedesspecies mosquitoes that can cause disease in humans, particularly when infection occurs in pregnancy where the virus can have a significant impact on the developing fetus. Despite this, there remains no prophylactic agent or therapeutic treatment for infection. Baicalein is a trihydroxyflavone, that is found in some traditional medicines commonly used in Asia, and has been shown to have several activities including antiviral properties. Importantly, studies have shown baicalein to be safe and well tolerated in humans, increasing its potential utilization.Methods: This study sought to determine the anti-ZIKV activity of baicalein using a human cell line (A549). Cytotoxicity of baicalein was determined by the MTT assay, and the effect on ZIKV infection determined by treating A549 cells with baicalien at different time points in the infection process. Parameters including level of infection, virus production, viral protein expression and genome copy number were assessed by flow cytometry, plaque assay, western blot and quantitative RT-PCR, respectively.Results: The results showed that baicalein had a half-maximal cytotoxic concentration (CC₅₀) of > 800 µM, and a half-maximal effective concentration (EC₅₀) of 124.88 µM. Time-of-addition analysis showed that baicalein had an inhibitory effect on ZIKV infection at the adsorption and post-adsorption stages. Moreover, baicalein also exerted a significant viral inactivation activity on ZIKV (as well as on dengue virus and Japanese encephalitis virus) virions.Conclusion: Baicalein has now been shown to possess anti-ZIKV activity in a human cell line.

Zika virus (ZIKV) infection has been recognized to cause adverse sequelae in the developing fetus. Specially, this virus activates the excessive release of IL-1β causing inflammation and altered physiological functions in multiple organs. Although many attempts have been invested to develop vaccine, antiviral, and antibody therapies, development of agents focusing on limiting ZIKV-induced IL-1β release have not gained much attention. We aimed to study the effects of alpinetin (AP) on IL-1β production in human macrophage upon exposure to ZIKV. Our study demonstrated that ZIKV stimulated IL-1β release in the culture supernatant of ZIKV-infected cells, and AP could effectively reduce the level of this cytokine. AP exhibited no virucidal activities against ZIKV nor caused alteration in viral production. Instead, AP greatly inhibited intracellular IL-1β synthesis. Surprisingly, this compound did not inhibit ZIKV-induced activation of NF-κB and its nuclear translocation. However, AP could significantly inhibit ZIKV-induced p38 MAPK activation without affecting the phosphorylation status of ERK1/2 and JNK. These observations suggest the possibility that AP may reduce IL-1β production, in part, through suppressing p38 MAPK signaling. Our current study sheds light on the possibility of using AP as an alternative agent for treating complications caused by ZIKV infection-induced IL-1β secretion.