Quercetin-mediated Cell Cycle Arrest and Apoptosis Involving Activation of a Caspase Cascade through the Mitochondrial Pathway in Human Breast Cancer MCF-7 Cells

Chu-Chung Chou,Jai-Sing Yang,Hsu-Feng Lu,Siu-Wan Ip,Chyi Lo,Chih-Chung Wu,Jing-Pin Lin,Nou-Ying Tang,Jing-Gung Chung,Ming-Jen Chou,Ying-Hock Teng,Dar-Ren Chen 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 μM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 μM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 μM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56%to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and ΔΨ m and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.

Scaling up the in-hospital hepatitis C virus care cascade in Taiwan

( Chung-feng Huang ),( Pey-fang Wu ),( Ming-lun Yeh ),( Ching-i Huang ),( Po-cheng Liang ),( Cheng-ting Hsu ),( Po-yao Hsu ),( Hung-yin Liu ),( Ying-chou Huang ),( Zu-yau Lin ),( Shinn-cherng Chen ),( 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without. Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation. Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001). Conclusions: The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination. (Clin Mol Hepatol 2021;27:136-143)

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Effects of coffee intake on airway hypersensitivity and immunomodulation: an in vivo murine study

Wong Ying-Chi,Hsu Wen-Cheng,Wu Tzee-Chung,Huang Ching-Feng 한국영양학회 2023 Nutrition Research and Practice Vol.17 No.4

BACKGROUND/OBJECTIVES: Coffee is a complex chemical mixture, with caffeine being the most well-known bioactive substance. The immunomodulator y and anti-inflammator y properties of coffee and caffeine impact health in various aspects, including the respirator y system. The objective is to investigate the effects of coffee and caffeine on air way hyperresponsiveness and allergic reactions, as well as to analyze and compare associated cytokine profiles. MATERIALS/METHODS: BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and given OVA inhalation to induce air way hypersensitivity. Two weeks after sensitization, they were intragastrically gavaged with coffee or caffeine, both containing 0.3125 mg caffeine, daily for 4 weeks. Control mice were fed with double-distilled water. Serum OVA- specific antibody levels were measured beforehand and 5 weeks after the first gavage. Air way hyperresponsiveness was detected by whole body plethysmography after gavage. Cytokine levels of bronchoalveolar lavage and cultured splenocytes were analyzed. RESULTS: Coffee effectively suppressed T helper 2-mediated specific antibody response. Air way responsiveness was reduced in mice treated with either coffee or caffeine. Compared to the control, coffee significantly reduced OVA-specific immunoglobulin (Ig) G, IgG1 and IgE antibody responses (P < 0.05). Caffeine also attenuated specific IgG and IgG1 levels, though IgE level was unaffected. Coffee significantly reduced interleukin (IL)-4 and increased IL-10 concentration in spleen cells and bronchoalveolar lavage fluid (P < 0.05). CONCLUSIONS: Coffee effectively attenuated air way hyperresponsiveness and systemic allergic responses induced by OVA food allergen in mice. As a complex composition of bioactive substances, coffee displayed enhanced immunomodulator y and anti-inflammator y effects than caffeine.

Tumors Involving Skin, Soft Tissue and Skeletal Muscle: Benign, Primary Malignant or Metastatic?

Hsieh, Chi-Ying,Tsai, Huang-Wen,Chang, Chih-Chun,Lin, Tsuo-Wu,Chang, Ke-Chung,Chen, Yo-Shen Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Metastatic cancer with invasion of skin, soft tissue and skeletal muscle is not common. Examples presenting as soft tissue masses could sometimes lead to misdiagnosis with delayed or inappropriate management. The purpose of current study was to investigate clinical characteristics in the involvement of metastatic cancer. Materials and Methods: A total of 1,097 patients complaining of skin or soft tissue masses and/or lesions were retrospectively reviewed from January 2012 to June 2013. Tumors involving skin, soft tissue and skeletal muscle of head and neck, chest wall, abdominal wall, pelvic region, back, upper and lower extremities were included in the study. Results: Fifty-seven (5.2%) patients were recognized as having malignancies on histopathological examination. The most common involvement of malignancy was basal cell carcinoma, followed by cutaneous squamous cell carcinoma, sarcoma and melanoma. The most common anatomical location in skin and soft tissue malignancies was head and neck (52.6% of the malignancies). Four (0.36%) of the malignant group were identified as metastatic cancer with the primary cancer source from lung, liver and tonsil and the most common site was upper extremities. One of them unexpectedly expired during the operation of metastatic tumor excision at the scalp. Conclusions: Discrimination between benign and malignant soft tissue tumors is crucial. Performance of imaging study could assist in the differential diagnosis and the pre-operative risk evaluation of metastatic tumors involving skin, soft tissue and skeletal muscle.

Lipopolysaccharide-induced Autophagy Increases SOX2-positive Astrocytes While Decreasing Neuronal Differentiation in the Adult Hippocampus

Liu Wen-Chung,Wu Chih-Wei,Fu Mu-Hui,Tain You-Lin,Liang Chih-Kuang,Chen I-Chun,Hung Chun-Ying,Lee Yu-Chi,Wu Kay L.H. 한국뇌신경과학회 2022 Experimental Neurobiology Vol.31 No.5

Inflammation alters the neural stem cell (NSC) lineage from neuronal to astrogliogenesis. However, the underlying mechanism is elusive. Autophagy contributes to the decline in adult hippocampal neurogenesis under E. coli lipopolysaccharide (LPS) stimulation. SRY-box transcription Factor 2 (SOX2) is critical for NSC self-renewal and proliferation. In this study, we investigated the role of SOX2 in induced autophagy and hippocampal adult neurogenesis under LPS stimulation. LPS (5 ng•100 g-1•hour-1 for 7 days) was intraperitoneally infused into male Sprague–Dawley rats (8 weeks old) to induce mild systemic inflammation. Beclin 1 and autophagy protein 12 (Atg12) were significantly upregulated concurrent with decreased numbers of Ki67- and doublecortin (DCX)-positive cells in the dentate gyrus. Synchronically, the levels of phospho(p)-mTOR, the p-mTOR/mTOR ratio, p-P85s6k, and the p-P85s6k/P85s6k ratio were suppressed. In contrast, SOX2 expression was increased. The fluorescence micrographs indicated that the colocalization of Beclin 1 and SOX2 was increased in the subgranular zone (SGZ) of the dentate gyrus. Moreover, increased S100β-positive astrocytes were colocalized with SOX2 in the SGZ. Intracerebroventricular infusion of 3-methyladenine (an autophagy inhibitor) effectively prevented the increases in Beclin 1, Atg12, and SOX2. The SOX2+-Beclin 1+ and SOX2+-S100β+ cells were reduced. The levels of p-mTOR and p-P85s6k were enhanced. Most importantly, the number of DCX-positive cells was preserved. Altogether, these data suggest that LPS induced autophagy to inactivate the mTOR/P85s6k pathway, resulting in a decline in neural differentiation. SOX2 was upregulated to facilitate the NSC lineage, while the autophagy milieu could switch the SOX2-induced NSC lineage from neurogenesis to astrogliogenesis.

Effect of H2O and CO2 on NOx emission control for lean-burn engines by electrochemical-catalytic cells

Ta-Jen Huang,Chung-Ying Wu,De-Yi Chiang 한국공업화학회 2013 Journal of Industrial and Engineering Chemistry Vol.19 No.3

Lean-burn engines can offer superior fuel efficiency but require advanced technology for NOx emission control. Electrochemical-catalytic cell has been proposed for lean DeNOx. This work demonstrates that the DeNOx rate can be enhanced by the presence of H2O and/or CO2, and can increase with increasing H2O and CO2 concentrations, although the increased extent is quite small. In the low NOx concentration range,relatively constant DeNOx rates were observed and can result in zero NOx emissions, where the presence of H2O and CO2 has important enhancement effect. Higher temperature generally results in larger N2selectivity in the low NOx concentration region.

Association of AXIN1 With Parkinson’s Disease in a Taiwanese Population

Hwa-Shin Fang,Chih-Ying Chao,Chun-Chieh Wang,Wen-Lang Fan,Po-Jung Huang,Hon-Chung Fung,Yih-Ru Wu 대한파킨슨병및이상운동질환학회 2022 Journal Of Movement Disorders Vol.15 No.1

A meta-analysis of locus-based genome-wide association studies recently identified a relationship between AXIN1 and Parkinson’s disease (PD). Few studies of Asian populations, however, have reported such a genetic association. The influences of rs13337493, rs758033, and rs2361988, three PD-associated genetic variants of AXIN1, were investigated in the present study because AXIN1 is related to Wnt/β-catenin signaling.

Neural correlates of the popular music phenomenon: evidence from functional MRI and PET imaging

Chen, Qiaozhen,Zhang, Ying,Hou, Haifeng,Du, Fenglei,Wu, Shuang,Chen, Lin,Shen, Yehua,Chao, Fangfang,Chung, June-key,Zhang, Hong,Tian, Mei Springer-Verlag 2017 European journal of nuclear medicine and molecular Vol.44 No.6

<P>Popular music Gangnam Style can arouse pleasure experience and strong emotional response. The left putamen is positively correlated with the mood arousal level score under the Gangnam Style condition. Our results revealed characteristic patterns of brain activity associated with Gangnam Style, and may also provide more general insights into the music-induced emotional processing.</P>

Chrysophanol-induced Necrotic-like Cell Death through an Impaired Mitochondrial ATP Synthesis in Hep3B Human Liver Cancer Cells

Chien-Hang Ni,Jing-Gung Chung,Po-Yuan Chen,Hsu-Feng Lu,Jai-Sing Yang,Hui-Ying Huang,Shin-Hwar Wu,Siu-Wan Ip,Chin-Tung Wu,Su-Yin Chiang,Jaung-Geng Lin,W. Gibson Wood 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanolinduced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca2+ production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanolinduced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.