ABSTRACT
NF-κB activation is pivotal for the excess inflammation causing the critical condition and mortality of respiratory viral infection patients. This study was aimed to evaluate the effect of a banana plant extract (BPE) on suppressing NF-κB activity and acute lung inflammatory responses in mice induced by a synthetic double-stranded RNA viral mimetic, polyinosinic-polycytidylic acid (poly (I:C)). The inflammatory responses were analyzed by immunohistochemistry and HE stains and ELISA. The NF-κB activities were detected by immunohistochemistry in vivo and immunofluorescence and Western blot in vitro. Results showed that BPE significantly decreased influx of immune cells (neutrophils, lymphocytes, and total WBC), markedly suppressed the elevation of pro-inflammatory cytokines and chemokines (IL-6, RANTES, IFN-γ, MCP-1, keratinocyte-derived chemokine, and IL-17), and restored the diminished anti-inflammatory IL-10 in the bronchoalveolar lavage fluid (BALF) of poly (I:C)-stimulated mice. Accordingly, HE staining revealed that BPE treatment alleviated poly (I:C)-induced inflammatory cell infiltration and histopathologic changes in mice lungs. Moreover, immunohistochemical analysis showed that BPE reduced the pulmonary IL-6, CD11b (macrophage marker), and nuclear NF-κB p65 staining intensities, whilst restored that of IL-10 in poly (I:C)-stimulated mice. In vitro, BPE antagonized poly(I:C)-induced elevation of IL-6, nitric oxide, reactive oxygen species, NF-κB p65 signaling, and transient activation of p38 MAPK in human lung epithelial-like A549 cells. Taken together, BPE ameliorated viral mimic poly(I:C)-induced acute pulmonary inflammation in mice, evidenced by reduced inflammatory cell infiltration and regulation of both pro- and anti-inflammatory cytokines. The mechanism of action might closely associate with NF-κB signaling inhibition.
Subject(s)
Musa , Pneumonia , Mice , Humans , Animals , NF-kappa B , Poly I-C/pharmacology , Poly I-C/therapeutic use , Interleukin-10 , Interleukin-6 , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Cytokines , Inflammation/chemically induced , Inflammation/drug therapy , Chemokines , Anti-Inflammatory Agents/therapeutic useABSTRACT
Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in males worldwide. Early-stage PC patients can benefit from surgical, radiation, and hormonal therapies; however, once the tumor transitions to an androgen-refractory state, the efficacy of treatments diminishes considerably. Recently, the exploration of natural products, particularly dietary phytochemicals, has intensified in response to addressing this prevailing medical challenge. In this study, we uncovered a synergistic effect from combinatorial treatment with lovastatin (an active component in red yeast rice) and Antrodia camphorata (AC, a folk mushroom) extract against PC3 human androgen-refractory PC cells. This combinatorial modality resulted in cell cycle arrest at the G0/G1 phase and induced apoptosis, accompanied by a marked reduction in molecules responsible for cellular proliferation (p-Rb/Rb, Cyclin A, Cyclin D1, and CDK1), aggressiveness (AXL, p-AKT, and survivin), and stemness (SIRT1, Notch1, and c-Myc). In contrast, treatment with either AC or lovastatin alone only exerted limited impacts on the cell cycle, apoptosis, and the aforementioned signaling molecules. Notably, significant reductions in canonical PC stemness markers (CD44 and CD133) were observed in lovastatin/AC-treated PC3 cells. Furthermore, lovastatin and AC have been individually examined for their anti-PC properties. Our findings elucidate a pioneering discovery in the synergistic combinatorial efficacy of AC and clinically viable concentrations of lovastatin on PC3 PC cells, offering novel insights into improving the therapeutic effects of dietary natural products for future strategic design of therapeutics against androgen-refractory prostate cancer.
Subject(s)
Biological Products , Prostatic Neoplasms , Male , Humans , Androgens/metabolism , PC-3 Cells , Lovastatin/pharmacology , Cell Proliferation , Apoptosis , Prostatic Neoplasms/pathology , Biological Products/pharmacology , Biological Products/therapeutic use , Cell Line, TumorABSTRACT
Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial-mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, ß-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Cisplatin , Drug Resistance, Neoplasm , Lung Neoplasms , A549 Cells/drug effects , A549 Cells/metabolism , AMP-Activated Protein Kinases/metabolism , Antineoplastic Agents/adverse effects , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Fish Oils/metabolism , Fish Oils/pharmacology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Neoplastic Stem Cells , Phenotype , Saccharomyces cerevisiae/metabolism , Selenium/metabolism , Selenium/pharmacologyABSTRACT
Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated ß-catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.
Subject(s)
Adenocarcinoma of Lung/drug therapy , Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Resistance, Neoplasm/drug effects , Endoplasmic Reticulum Stress/drug effects , Fatty Acids, Omega-3/pharmacology , Gefitinib/pharmacology , Lung Neoplasms/drug therapy , Selenium/pharmacology , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Combinations , Endoplasmic Reticulum Chaperone BiP , Epithelial-Mesenchymal Transition/drug effects , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathologyABSTRACT
A small pilot study of the fermented soybean extract MicrSoy-20(MS-20) demonstrated its ability to restore chemotherapy-induced immunosuppression and improve quality of life (QoL). This randomized, cross-over, comparative trial was conducted to confirm the effects of MS-20 on QoL and to understand its underlying mechanism when used in conjunction with chemotherapy. One hundred forty-three patients undergoing cancer chemotherapy were randomly assigned to 2 groups. Group 1 was administered MS-20 for 1 wk followed by 3 wk of concomitant MS-20 plus chemotherapy. Group 2 was administered chemotherapy for 3 wk. QoL was assessed by the EORTC/QLQ-C30 questionnaire and visual analogue scales (VAS). Changes in immunological parameters and antioxidant profiles were also examined. Significant increases were observed in EORTC/QLQ-C30 scores for physical (4.45, P = 0.023) and social (3.99, P = 0.023) functioning in Group 1 patients compared to Group 2 patients. VAS scores for fatigue and appetite loss significantly improved with MS-20 treatment (P < 0.001). Group 1 patients exhibited smaller decreases in peripheral blood mononuclear cells compared to Group 2 patients (P = 0.026). Other immunological parameters, antioxidant, and safety profiles were not significantly different between treatment groups. Addition of MS-20 as an adjuvant to chemotherapy can be effective in improving QoL for cancer patients.
Subject(s)
Appetite/drug effects , Fatigue/drug therapy , Neoplasms/drug therapy , Plant Extracts/pharmacology , Adult , Aged , Chemotherapy, Adjuvant/methods , Cross-Over Studies , Endpoint Determination , Fatigue/chemically induced , Female , Humans , Leukocytes, Mononuclear , Male , Middle Aged , Pilot Projects , Prospective Studies , Quality of Life , Glycine max/chemistry , Surveys and Questionnaires , Visual Analog Scale , Young AdultABSTRACT
Iron overload is common in myelodysplastic syndrome (MDS) patients, and an accumulation of evidence shows that iron chelation may have benefits in these patients. However, discussion and consensus about iron chelation therapy (ICT) for MDS patients is lacking in Taiwan and other Southeast Asian countries. An Expert Panel in Taiwan was organized in 2011 to develop iron overload guidelines and provide a uniform reference for physicians treating MDS patients with iron overload, with specific regard to when to initiate ICT, in which patients, and the clinical and scientific rationale behind its use.
Subject(s)
Iron Overload/drug therapy , Iron Overload/etiology , Myelodysplastic Syndromes/complications , Chelation Therapy/methods , Hematopoiesis/drug effects , Humans , Iron Chelating Agents/therapeutic use , Iron Overload/complications , Myelodysplastic Syndromes/epidemiology , Practice Guidelines as Topic , Survival Analysis , Taiwan/epidemiologyABSTRACT
Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3-4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.
Subject(s)
Acetylcysteine/therapeutic use , Antineoplastic Agents/adverse effects , Chemotherapy, Adjuvant/adverse effects , Colorectal Neoplasms/drug therapy , Free Radical Scavengers/therapeutic use , Neuroprotective Agents/therapeutic use , Organoplatinum Compounds/adverse effects , Adult , Aged , Colorectal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Oxaliplatin , Pilot Projects , Postoperative CareABSTRACT
BACKGROUND: Irinotecan (CPT11) has established activity against advanced colorectal cancer without cross-resistance with 5-fluorouracil + leucovorin-based therapy. We conducted this pilot study to evaluate the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil (5-FU) for patients in whom combination treatment with oxaliplatin with 5-FU + leucovorin has failed. METHODS: Patients were enrolled in this study after oxaliplatin treatment had failed. The treatment protocol consisted of CPT11 (180 mg/m(2) for 90 min) on day 1 and a 2 h infusion of 200 mg/m(2) leucovorin followed by 400 mg/m(2) 5-FU as an intravenous bolus injection plus a 22 h continuous infusion of 600 mg/m(2) 5-FU. This regimen was repeated for two consecutive days every 2 weeks. RESULTS: A total of 18 patients were eligible for this study and in total 144 cycles of therapy (median eight cycles) were given to these patients. Four patients (22.2%; 95% CI: 8-36.4%) achieved an objective response of partial remission (PR) and an additional seven obtained stable disease (SD) status or minor response. The median duration of response was 8 months and 14 patients were alive at the end of the study. Hematological toxicity (neutropenia) was the most common serious side effect (29.2%), followed by gastrointestinal effects (diarrhea, 28.5%). Grade II-III diarrhea was experienced for at least one cycle by each patient. CONCLUSIONS: The results of treatment for patients after oxaliplatin failure are encouraging and this treatment protocol is also well tolerated by previously heavily treated patients.