Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Yao, Chih-Jung,Chow, Jyh-Ming,Chuang, Shuang-En,Chang, Chia-Lun,Yan, Ming-De,Lee, Hsin-Lun,Lai, I-Chun,Lin, Pei-Chun,Lai, Gi-Ming The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells

Chih-Jung Yao,Jyh-Ming Chow,Shuang-En Chuang,Chia-Lun Chang,Ming-De Yan,Hsin-Lun Lee,I-Chun Lai,Pei-Chun Lin,Gi-Ming Lai 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG- 135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

Coronary Cameral Fistula and Anomalous Right Coronary Artery: A Case Report

Ng Pan Pan,Chow Boris Chun Kei,Cheung Stephen Chi Wai,Ng Ming-Yen 아시아심장혈관영상의학회 2022 Cardiovascular Imaging Asia Vol.6 No.1

Coronary artery anomalies are uncommon with variable clinical significance. We present a case of 49-year-old gentleman with atypical chest pain, who was found to have single left coronary artery, anomalous right coronary artery with pre-pulmonic course, as well as coronary- cameral fistula on coronary computed tomography angiogram (CCTA). CCTA demonstrated no significant coronary artery stenosis to suggest ischemic heart disease nor ventricular dysfunction to suggest significant hemodynamic consequence secondary to the coronary anomalies.

Individual Contribution in Brain-storming: Does Group Composition Make a Difference?

Wai-Kin Yip,Chun-Ming Chow,Kin-Wai Cheng,Chi-Ping Cheuk,Catherine McBride-Chang 대한사고개발학회 2007 The International Journal of Creativity & Problem Vol.17 No.2

Factors affecting individual performance in group tasks such as social loafing and social facilitation have been widely investigated. Past studies compared groups made up of friends or strangers based on prior acquaintance before the experiment, without directly manipulating the level of group cohesiveness. Based on Karau and William’s (1997) rationale about the effect of group cohesiveness on social facilita- tion and social loafing, we tested two hypotheses: (1) When individual members do brain-storming in high cohesiveness group, they work harder and generate more ideas (social facilitation). (2) When individual members do brain-storming in low cohesiveness group, they work less hard and generate fewer ideas (social loafing). Results supported the second hypothesis, but failed to support the first one.

Splenic T1-Mapping for Predicting Adenosine Stress Adequacy in Cardiac Magnetic Resonance Myocardial Perfusion Imaging: A Validation and Reproducibility Study

Wan Fiona Fong-ying,Yeung Catherine Ming-mun,Yam Pak-ki,Ng Pan Pan,Chow Boris Chun Kei,Chiang Jeanie Betsy,Lee Jonan Chun-yin,Cheung Kenneth Kai-yat,Ng Ming-yen 아시아심장혈관영상의학회 2022 Cardiovascular Imaging Asia Vol.6 No.3

Objective:Splenic switch-off (SSO) sign has been utilized as a surrogate marker of adequate stress but can only be assessed after first-pass perfusion imaging. A study previously reported that drop in T1spleen ≥30 ms during adenosine infusion predicts presence of SSO, but this finding has not been externally validated. This study aimed to prospectively validate whether drop in T1spleen ≥30 ms is a reliable marker of SSO and hence adequate stress, and to assess reproducibility of T1spleen measurements. Materials and Methods: Data of fifty consecutive patients undergoing stress cardiac magnetic resonance were prospectively collected. Native T1-maps were acquired at rest and at 2.5 min after adenosine infusion in short axis slices, followed by perfusion images at 3 min. To measure T1spleen pre- and post-adenosine infusion, regions of interest were manually placed to include most splenic tissue. Adenosine stress adequacy was evaluated by visual SSO assessment and semi-quantitative splenic perfusion analysis. Results:A significant association was found between a drop in T1spleen of ≥30 ms and SSO response (p<0.001). There was excellent correlation between SSO response and semiquantitative perfusion change in spleen (rho=0.847, p<0.001). Inter-observer and intra-observer agreement for measurement of ΔT1spleen values were excellent, with intra-class correlation coefficients of 0.987 and 0.995, respectively. By receiver-operating characteristic analysis, the optimal cut-off value of ΔT1spleen for predicting presence of SSO was -28 ms, with area under the curve=0.76 (p=0.002). Conclusion:Splenic T1-mapping is accurate and reproducible for predicting SSO, potentially allowing optimization of adenosine dosage for adequate stress.