Hsu-Shan Huang

Taipei Medical University | TMU · College of Medical Science and Technology

Tridax procumbens (cotton buttons) is a flowering plant with a medicinal reputation for treating infections, wounds, diabetes, and liver and kidney diseases. The present research was conducted to evaluate the possible protective effects of the T. procumbens methanolic extract (TPME) on an experimentally induced type 2 diabetes rat model. Wistar rat...

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated coronavirus disease 2019 (COVID-19) infection remains a global pandemic and health emergency with overwhelming social and economic impacts throughout the world. Therapeutics for COVID-19 are limited to only remdesivir; therefore, there is a need for combined, multidisciplinar...

Colorectal cancer (CRC) is one of the most common cancers, and it frequently metastasizes to the liver and lymph nodes. Despite major advances in treatment modalities, CRC remains a poorly characterized biological malignancy, with high reported cases of deaths globally. Moreover, cancer stem cells (CSCs) and their microenvironment have been widely...

Our previous study found that 2-phenyl-4-quinolone (2-PQ) derivatives are antimitotic agents, and we adopted the drug design concept of scaffold hopping to replace the 2-aromatic ring of 2-PQs with a 4-aromatic ring, representing 4-phenyl-2-quinolones (4-PQs). The 4-PQ compounds, whose structural backbones also mimic analogs of podophyllotoxin (PPT...

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Acute myeloid leukemia (AML) is a type of leukemia with an aggressive phenotype, that commonly occurs in adults and with disappointing treatment outcomes. Genetic alterations were implicated in the etiology of cancers and form the basis for defining patient prognoses and guiding targeted therapies. In the present study, we leveraged bulk and single...

The quest for novel anti-diabetic medication from medicinal plants is very important since they contain bioactive phytochemicals that offer better activity and safety compared to conventional therapy. In the present study, in vitro, in vivo and in silico approaches were explored to evaluate the anti-inflammatory, antioxidants, and hypoglycemic acti...

The present study evaluated the polyphenolic contents and hypoglycemic, antioxidant, and anti-inflammatory effects of the diethyl ether fraction of Thespesia garckeana using various in vitro and in vivo models. Total phenol and flavonoid contents of the extract were 613.65 ± 2.38 and 152.83 ± 1.56 mg/100 g dry weight, respectively. The extract exhi...

Coronavirus disease 2019 (COVID-19) is a global pandemic and respiratory infection that has enormous damage to human lives and economies. It is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a non-pair-stranded positive-sense RNA virus. With increasing global threats and few therapeutic options, the discovery of new potenti...

Lung cancer poses a serious threat to human health and has recently been tagged the most common malignant disease with the highest incidence and mortality rate. Although epidermal growth factor (EGFR)-tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of advanced non-small cell lung cancer (NSCLC) patients with EGFR mutatio...

Current anticancer treatments are inefficient against glioblastoma multiforme (GBM), which remains one of the most aggressive and lethal cancers. Evidence has shown the presence of glioblastoma stem cells (GSCs), which are chemoradioresistant and associated with high invasive capabilities in normal brain tissues. Moreover, accumulating studies have...

Renal tubulointerstitial lesions (TILs), a common pathologic hallmark of chronic kidney disease that evolves to end-stage renal disease, is characterized by progressive inflammation and pronounced fibrosis of the kidney. However, current therapeutic approaches to treat these lesions remain largely ineffectual. Previously, we demonstrated that eleva...

Cholangiocarcinomas (CHOLs), hepatobiliary malignancies, are characterized by high genetic heterogeneity, a rich tumor microenvironment, therapeutic resistance, difficulty diagnosing, and poor prognoses. Current knowledge of genetic alterations and known molecular markers for CHOL is insufficient, necessitating the need for further evaluation of th...

Glioblastoma (GBM) is one of the most aggressive brain malignancies with high incidences of developing treatment resistance, resulting in poor prognoses. Glioma stem cell (GSC)-derived exosomes are important players that contribute to GBM tumorigenesis and aggressive properties. Herein, we investigated the inhibitory roles of GBM-N019, a novel smal...

Objective: Endothelial cell (EC) activation facilitates leukocyte adhesion to vascular walls, which is implicated in a variety of cardiovascular diseases and is a target for prevention and treatment. Despite the development of anti-inflammatory medications, cost-effective therapies with significant anti-inflammatory effects and lower organ toxicit...

Purpose: Breast cancer is the most frequently diagnosed cancer globally, and the leading cause of cancer-associated mortality among women. The efficacy of most clinical chemotherapies is often limited by poor pharmacokinetics and the development of drug resistance by tumors. In a continuing effort to explore small molecules as alternative therapie...

Genetic and environmental factors play important roles in cancer progression, metastasis, and drug resistance. Herein, we used a multiomics data analysis to evaluate the predictive and prognostic roles of genetic and epigenetic modulation of c-MET (hepatocyte growth factor receptor)/epidermal growth factor receptor (EGFR) in colorectal cancer (CRC)...

Tumor recurrence from cancer stem cells (CSCs) and metastasis often occur post-treatment in colorectal cancer (CRC), leading to chemoresistance and resistance to targeted therapy. MYC is a transcription factor in the nuclei that modulates cell growth and development, and regulates immune response in an antitumor direction by mediating programmed de...

In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide‐linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6‐(2,4‐difluorophenyl)‐3‐(3‐(trifluoromethyl)phenyl)‐2H‐benzo[e][1,3]oxazine‐2,4(3H)‐dione (Cf‐02) (a) reduced serum levels of IgG anti‐ds...

Mechanisms of breast cancer progression and invasion, often involve alteration of hormonal signaling, and upregulation and/or activation of signal transduction pathways that input to cell cycle regulation. Herein, we describe a rationally designed first-in-class novel small molecule inhibitor for targeting oncogenic and hormonal signaling in ER-pos...

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathways are critical for normal human physiology, and any alteration in their regulation leads to several human cancers. These pathways are well interco...

Ovarian cancer is often detected at the advanced stages at the time of initial diagnosis. Early-stage diagnosis is difficult due to its asymptomatic nature, where less than 30% of 5-year survival has been noticed. The underlying molecular events associated with the disease’s pathogenesis have yet to be fully elucidated. Thus, the identification of...

Background The application of computational and multi-omics approaches has aided our understanding of carcinogenesis and the development of therapeutic strategies. NSC765598 is a novel small molecule derivative of salicylanilide. This study aims to investigate the ligand-protein interactions of NSC765598 with its potential targets and to evaluate i...

Despite management efforts with standard surgery, radiation, and chemotherapy, glio-blastoma multiform (GBM) remains resistant to treatment, which leads to tumor recurrence due to glioma stem cells (GSCs) and therapy resistance. In this study, we used random computer-based prediction and target identification to assess activities of our newly synth...

As part of our research on developing multi-target small molecule anticancer agents, we designed, synthesized, and biologically evaluated a series of novel diversified analogues based on our thiadiazole-fused anthraquinone lead compound NSC745885. We initially screened our compounds based on their cytotoxicities against two prostate cancer cell lin...

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis...

Despite advancements in diagnostic and standard treatment modalities, including surgery, radiotherapy, and chemotherapy, overall survival rates of advanced-stage head and neck squamous cell carcinoma (HNSCC) patients have remained stagnant for over three decades. Failure of these treatment modalities, coupled with post-therapy complications, unders...

Colorectal cancer represents one of the most prevalent malignancies globally, with an estimated 140,000 new cases in the United States alone in 2019. Despite advancements in interventions, drug resistance occurs in virtually all patients diagnosed with late stages of colon cancer. Amplified epidermal growth factor receptor (EGFR) signaling is one o...

Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potent...

Metastatic castration-resistant prostate cancer (CRPC) is currently incurable. Cancer growth and progression is intimately affected by its interaction with host microenvironment. Co-targeting of the stroma and prostate cancer is therefore an emerging therapeutic strategy for metastatic CRPC. Cancer-induced osteoclastogenesis is known to contribute...

In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory fl...

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E...

The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG ,and U87MG cells) and investigate the underlying molecular mech...

The bone destruction disease including osteoporosis and rheumatoid arthritis are caused by the imbalance between osteoblastogenesis and osteoclastogenesis. Inhibition of the NF-κB pathway was responsible for decreased osteoclastogenesis. Recently many studies indicated that niclosamide, the FDA approved an antihelminth drug, inhibits prostate and b...

We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the...

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that TC-N19 (N19), a novel dual inhibitor of EGFR and cMET, efficient...

Several 9-chloro-11H-indeno[1,2-c]quinolin-11-one derivatives have been designed which is replacing side chains with different groups containing oxygen, nitrogen or sulfur atoms. Substitution of C-6 on the starting structure, 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one, using apposite nucleophilic group with a suitable base or acid could be obtai...

The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 valu...

Cytotoxicity of NSC745885, NSC757963 and doxorubicin towards the normal cardiac myoblast H9c2 cells. (TIF)

1H-NMR spectrum of NSC757963. (TIF)

Mean GI50 values (Molar) and selectivity ratios of NSC745885 and NSC757963 obtained from the JFCR 39 cell line experiments. a The average value of GI50 of every cell line panel tested in the five-dose JFCR 39 cell line screen experiments. b The average value of GI50 of all of the tested cell lines in the five-dose JFCR 39 cell line screen experimen...

JFCR drugs with similar activity profiles to NSC757963. a This coefficient ranges from -1 to +1. Compounds with positive coefficient values approaching 1 have high similarities with the test compound, while those with negative coefficient values approaching -1 have high differences with the test compound, and a value of zero indicates no correlatio...

Mean Graph of the log10 values (Molar) of GI50, TGI and LC50 of NSC745885 obtained from the NCI 60 cell line experiments. X-axis is constructed based on the log10 scale, the zero represents log10 of the mean values (MID or MG-MID) of each of the GI50, TGI and LC50. Values to the right side of zero indicate more sensitivity of the cell lines to the...

HPLC chromatogram of NSC745885 showing purity of 98.06%. (TIF)

Synthesis scheme of NSC745885 and NSC757963. (TIF)

HPLC chromatogram of NSC757963 showing purity of 95.96%. (TIF)

Mean GI50 values (Molar) and selectivity ratios of NSC745885 and NSC757963 obtained from the NCI 60 cell line experiments. a The average value of GI50 of every cell line panel tested in the five-dose NCI 60 cell line screen experiments. b The average value of GI50 of all of the tested cell lines in the five-dose NCI 60 cell line screen experiments...

NCI STANDARD AGENTS with similar activity profiles to NSC745885. a Only compounds showing salient correlations with NSC745885 were selected and displayed in this table. Compounds appearing more than once in the COMPARE analysis results (due to difference in number of tested cell lines or in the hiConc of the compared experiments) were not included...

JFCR drugs with similar activity profiles to NSC745885. a This coefficient ranges from -1 to +1. Compounds with positive coefficient values approaching 1 have high similarities with the test compound, while those with negative coefficient values approaching -1 have high differences with the test compound. (DOCX)

Mean Graph of the log10 values (Molar) of GI50, TGI and LC50 of NSC745885 obtained from the JFCR 39 cell line experiments. X-axis is constructed based on the log10 scale; log10 of the mean values (MG-MID) of each of GI50, TGI and LC50 are represented by the zero on the X-axis. Delta values are the difference between the MG-MID and the log10 of each...

Mean Graph of the log10 values (Molar) of GI50, TGI and LC50 of NSC757963 obtained from the NCI 60 cell line experiments. X-axis is constructed based on the log10 scale, the zero represents log10 of the mean values (MID or MG-MID) of each of the GI50, TGI and LC50. Values to the right side of zero indicate more sensitivity of the cell lines to the...

Mean Graph of the log10 values (Molar) of GI50, TGI and LC50 of NSC757963 obtained from the JFCR 39 cell line experiments. X-axis is constructed based on the log10 scale; log10 of the mean values (MG-MID) of each of GI50, TGI and LC50 are represented by the zero on the X-axis. Delta values are the difference between the MG-MID and the log10 of each...

1H-NMR spectrum of NSC745885. (TIF)

NCI MARKETED DRUGS with similar activity profiles to NSC745885. a Only compounds showing salient correlations with NSC745885 were selected and displayed in this table. Compounds appearing more than once in the COMPARE analysis results (due to difference in number of tested cell lines or in the hiConc of the compared experiments) were not included i...

NCI STANDARD AGENTS with similar activity profiles to NSC757963. a Only compounds showing salient correlations with NSC757963 were selected and displayed in this table. Compounds appearing more than once in the COMPARE analysis results (due to difference in number of tested cell lines or in the hiConc of the compared experiments) were not included...

A series of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium derivatives was synthesized and evaluated for osteoclast inhibition using a TRAP-staining assay. Among them, two compounds, LCCY-13 and LCCY-15, dose-dependently suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Moreover, the cytotoxici...