Review
Genetics & Heredity
Shixiong Wei, Jialin Li, Mingbo Tang, Kewei Zhang, Xinliang Gao, Linan Fang, Wei Liu
Summary: STAT3 is a transcription factor with important functions in normal and transformed cells, especially in cancer stem cells. It is associated with p63 protein and plays a role in regulating CSC properties.
FRONTIERS IN GENETICS
(2022)
Review
Medicine, Research & Experimental
Sepideh Mirzaei, Mohammad Hossein Gholami, Mahmood Khaksary Mahabady, Noushin Nabavi, Amirhossein Zabolian, Seyed Mohammad Banihashemi, Amirabbas Haddadi, Maliheh Entezari, Kiavash Hushmandi, Pooyan Makvandi, Saeed Samarghandian, Ali Zarrabi, Milad Ashrafizadeh, Haroon Khan
Summary: Effective cancer therapy requires the identification of signaling networks, with STAT3 playing a significant role in promoting proliferation, invasion, chemoresistance, and metastasis in bladder cancer cells. Inhibiting STAT3 may enhance chemotherapy efficacy by overcoming chemoresistance in BC. Multiple molecular pathways and non-coding RNAs act as upstream regulators of STAT3 in BC cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Immunology
Amr Allam, Marina Yakou, Lokman Pang, Matthias Ernst, Jennifer Huynh
Summary: This article discusses the relationship between cancer-associated fibroblasts (CAFs) and signal transducer and activator of transcription 3 (STAT3) in the tumor microenvironment, as well as their impact on tumor growth, immune suppression, and metastatic spread. Research suggests that CAF-intrinsic STAT3 activity is closely associated with tumor progression.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Feng Zhou, Fanyun Zhu, Tianru Zhu, Zhucheng Zhao, Luyao Li, Shichong Lin, Haiyang Zhao, Lehe Yang, Chengguang Zhao, Liangxing Wang, Jifa Li, Xiaoying Huang
Summary: AT7519, a CDK inhibitor, exhibits great anti-tumor effects in lung cancer by blocking IL-6/STAT3 pathway and inhibiting cell proliferation and inducing apoptosis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Peng He, Ying Miao, Yue Sun, Aiwu Bian, Wangrui Jin, Jiangnan Ye, Huang Chen, Jia He, Yangrui Peng, Haijun Gu, Mingyao Liu, Zhengfang Yi, Yihua Chen
Summary: This study describes the design, synthesis, and structure-activity relationship studies of triaromatic heterocyclic derivatives as potent dual phosphorylation STAT3 inhibitors. The best compound 3h (HP590) was discovered with high inhibitory activity against p-Tyr(705) and p-Ser(727), resulting in the growth inhibition of gastric cancer both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhen Yu, Shixin Chan, Xu Wang, Ming Wang, Rui Sun, Zhenglin Wang, Xiaomin Zuo, Jiajie Chen, Huabing Zhang, Wei Chen
Summary: The combined therapy of 5-fluorouracil (5-FU) and rutaecarpine (RUT) showed significant inhibition of proliferation, migration, and anti-apoptotic ability of colorectal cancer (CRC) cells, both in vivo and in vitro. It was found that the therapy reduced the phosphorylation of STAT3 and influenced the STAT3 signaling pathway, leading to downregulation of c-Myc, CDK4, and Bcl-2 expression while enhancing cleaved caspase-3 expression.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Article
Oncology
Huang Chen, Wenbo Zhou, Aiwu Bian, Qiansen Zhang, Ying Miao, Xuan Yin, Jiangnan Ye, Shifen Xu, Chaowen Ti, Zhenliang Sun, Jianghua Zheng, Yihua Chen, Mingyao Liu, Zhengfang Yi
Summary: This study identifies a novel drug called WB436B as a selective STAT3 inhibitor for the treatment of pancreatic cancer. WB436B effectively inhibits tumor growth and metastasis, providing hope for the treatment of pancreatic cancer.
CLINICAL CANCER RESEARCH
(2023)
Review
Cell Biology
Yun Liu, Shijie Liao, Samuel Bennett, Haijun Tang, Dezhi Song, David Wood, Xinli Zhan, Jiake Xu
Summary: STAT3, a key protein involved in cell growth, differentiation, and survival, is overexpressed in osteosarcoma and various cancers. Its constitutive activation leads to upregulation of oncogenes, affecting processes such as transformation, proliferation, and metastasis.
CELL PROLIFERATION
(2021)
Review
Cardiac & Cardiovascular Systems
Lan Wu, Zhizheng Li, Yanfei Li
Summary: STAT3, as a transcription factor and signaling molecule, plays an important role in cardiac disease and protection. It regulates the expression of genes involved in oxidation, apoptosis, inflammation, and fibrosis. Additionally, it is also targeted and regulated by miRNAs, which further modulate the mRNA expression profiles in cardiomyocytes and impact cardiac disease and protection.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Chemistry, Medicinal
Peng He, Aiwu Bian, Ying Miao, Wangrui Jin, Huang Chen, Jia He, Liting Li, Yue Sun, Jiangnan Ye, Zhengfang Yi, Wenbo Zhou, Yihua Chen
Summary: This study reports the discovery of a series of novel STAT3 dual phosphorylation inhibitors with an indole-containing tetra-aromatic heterocycle scaffold. The optimal compound 4c showed desirable ADME properties and highly potent antitumor activities in vitro and in vivo. It has the potential to be a useful treatment option for pancreatic cancer as a STAT3 dual phosphorylation inhibitor.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Woong Sub Byun, Eun Seo Bae, Jinsheng Cui, Hyen Joo Park, Dong-Chan Oh, Sang Kook Lee
Summary: Pulvomycin effectively inhibits cell proliferation, induces cell cycle arrest and apoptosis by suppressing STAT3 activation, significantly inhibits invasion and migration of TNBC cells, and in combination with docetaxel effectively inhibits tumor growth in xenograft mouse model through STAT3 regulation.
Article
Oncology
Xining Zhao, Fei Chen
Summary: Propofol suppresses the viability of colorectal cancer cells by downregulating STAT3 expression, inhibiting cell proliferation and colony formation, and altering iron and ROS levels. Additionally, propofol affects the expression of proteins involved in ferroptosis, ultimately leading to ferroptosis in CRC cells.
Review
Oncology
Ranzhiqiang Yang, Yinghui Song, Kashif Shakoor, Weimin Yi, Chuang Peng, Sulai Liu
Summary: Intrahepatic cholangiocarcinoma (ICC) is a primary malignant liver tumor with a poor prognosis, characterized by neoplastic transformation of intrahepatic biliary epithelial cells. Signal transducer and activator of transcription 3 (STAT3) is an important oncogene that may serve as a target for ICC treatment. Further research is needed to improve understanding of STAT3 and its role in ICC development.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Immunology
Kosuke Miyauchi, Sewon Ki, Masao Ukai, Yoshie Suzuki, Kentaro Inoue, Wataru Suda, Takeshi Matsui, Yoshihiro Ito, Kenya Honda, Haruhiko Koseki, Osamu Ohara, Reiko J. Tanaka, Mariko Okada-Hatakeyama, Masato Kubo
Summary: The study suggests that STAT3 signaling in keratinocytes is essential for maintaining skin homeostasis by negatively regulating the expression of hair follicle-specific keratin genes. Expression patterns associated with dermatitis onset were observed under specific conditions, indicating the involvement of Toll-like receptor-mediated inflammatory responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Mehrdokht Sadrkhanloo, Maliheh Entezari, Sima Orouei, Marzieh Ghollasi, Nikoo Fathi, Shamin Rezaei, Elahe Sadat Hejazi, Amirabbas Kakavand, Hamidreza Saebfar, Mehrdad Hashemi, Mohammad Ali Sheikh Beig Goharrizi, Shokooh Salimimoghadam, Mohsen Rashidi, Afshin Taheriazam, Saeed Samarghandian
Summary: Epithelial-to-mesenchymal transition (EMT) mechanism is responsible for tumor metastasis and inhibition of this process improves prognosis. STAT3 signaling is shown to promote EMT-mediated cancer migration and invasion, and its inhibition suppresses cancer metastasis and improves therapy response.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Chien-Han Yuan, Yi-Ling Ma, Po-Chang Shih, Chao-Ting Chen, Shu-Yu Cheng, Chieh-Yu Pan, Yen-Hsuan Jean, Yih-Min Chu, Sung-Chun Lin, Yu-Cheng Lai, Hsiao-Mei Kuo
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Oncology
Ying-Fa Chen, Po-Chang Shih, Hsiao-Mei Kuo, San-Nan Yang, Yen-You Lin, Wu-Fu Chen, Shiow-Jyu Tzou, Hsin-Tzu Liu, Nan-Fu Chen
Review
Pharmacology & Pharmacy
Po-Chang Shih, Kuo-Ching Mei
Summary: Chemoresistance resulting from cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) leads to inconsistent chemotherapeutic efficacy. The presence of CSCs and EMT allows cancer cells to switch between differentiated and stem-like states, known as cellular plasticity. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is increasingly recognized as a major factor in CSCs and EMT, with preclinical studies showing reversal of chemoresistance through STAT3 pathway inhibition. This review focuses on mechanisms involving STAT3 and its target genes in regulating EMT, and also discusses the status of clinical trials using STAT3 pathway inhibitors.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Chou-Yuan Ko, Po-Chang Shih, Po-Wei Huang, Yi-Hsin Lee, Yen-Fu Chen, Ming-Hong Tai, Chi-Hao Liu, Zhi-Hong Wen, Hsiao-Mei Kuo
Summary: Sinularin was found to effectively inhibit the growth of hepatocellular carcinoma SK-HEP-1 cells at a concentration of 10 μM, inducing DNA fragmentation and apoptosis, as well as affecting cell migration and colony formation. Additionally, it altered the expression levels of various proteins related to cell signaling and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yen-Po Chen, Po-Chang Shih, Chien-Wei Feng, Chang-Cheng Wu, Kuan-Hao Tsui, You-Hsien Lin, Hsiao-Mei Kuo, Zhi-Hong Wen
Summary: The antimicrobial peptide pardaxin demonstrated promising anticancer activity in ovarian cancer cells by inducing apoptosis, enhancing ROS production, and modulating autophagy, suggesting its potential as a novel therapeutic agent for ovarian cancer.
Review
Pharmacology & Pharmacy
Po-Chang Shih
Summary: This article discusses the role of STAT3 in radioresistance and its relationship with the four Rs of radiotherapy. It is found that the STAT3 pathway inhibitor napabucasin antagonizes cancer stemness and radioresistance. The proposed mechanisms suggest that upstream and downstream effector proteins of STAT3 are involved in these processes.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Tsu-Jen Kuo, Yen-Hsuan Jean, Po-Chang Shih, Shu-Yu Cheng, Hsiao-Mei Kuo, Yi-Ting Lee, Yu-Cheng Lai, Chung-Chih Tseng, Wu-Fu Chen, Zhi-Hong Wen
Summary: This study evaluated the effects of marine-derived triterpene stellettin B on oral squamous cell carcinoma (OSCC) cells and found that stellettin B induced cell death through mechanisms including endoplasmic reticulum stress, mitochondrial stress, apoptosis, and autophagy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shih-Yuan Hsu, Zhi-Hong Wen, Po-Chang Shih, Hsiao-Mei Kuo, Sung-Chun Lin, Hsin-Tzu Liu, Yi-Hsin Lee, Yi-Jen Wang, Wu-Fu Chen, Nan-Fu Chen
Summary: This study evaluated the effects of sinularin, a marine-derived product, on glioblastoma multiforme (GBM). The results showed that sinularin can induce cell death in GBM cells and inhibit angiogenesis. These findings suggest that sinularin may be a potential drug for treating GBM.
Article
Medicine, Research & Experimental
Zhi-Hong Wen, Hsiao-Mei Kuo, Po-Chang Shih, Ling-Chen Hsu, Jimmy Ming-Jung Chuang, Nan-Fu Chen, Hsi-Wen Sun, Hsin-Tzu Liu, Chun-Sung Sung, Wu-Fu Chen
Summary: This study evaluated the effects of isoaaptamine and aaptamine on cell viability in glioblastoma multiforme (GBM) cell lines. The results showed that isoaaptamine was more potent than aaptamine in these cell lines, with GBM 8401 being the most sensitive. The study also found that isoaaptamine could induce apoptosis, increase oxidative stress, disrupt mitochondrial function, and trigger autophagy in GBM cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Po-Chang Shih, Miyako Naganuma, Yosuke Demizu, Mikihiko Naito
Summary: Transcription factors (TFs) and RNA-binding proteins (RBPs) have been challenging to target with drugs due to their lack of ligand-binding sites and flat, narrow protein surfaces. However, protein-specific oligonucleotides have shown promise as a means to target TFs and RBPs, and the emerging PROTAC technology utilizes these oligonucleotides as warheads. This review article discusses the current state and future development of oligonucleotide-based protein degraders that rely on the ubiquitin-proteasome system or proteases.
Article
Biochemistry & Molecular Biology
Po-Chang Shih, Miyako Naganuma, Genichiro Tsuji, Yosuke Demizu, Mikihiko Naito
Summary: Proteolysis-targeting chimera (PROTAC) technology is a disruptive innovation in drug development that can be used to degrade DNA-binding proteins such as transcription factors. In this study, oligonucleotide-warheaded PROTACs were used to induce the degradation of STAT3, a hard-to-target protein, showing potential therapeutic applications against cancer.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Po-Chang Shih, Yi-Wen Mao, Jhe-Wei Hu, Han-Yi Hsieh, Tsai-Miao Shih, Lu-Ping Lu, Wei-Hua Chang, Chan-Hui Huang, Chia-Hung Lin, Chih-Hung Lin, Peng Tan, Ya-Ching Yang, Ming-Hong Chien, Chen-Che Su, Cheng-Hsin Yeh, Pei-Yun Chuang, Tien-Lan Hsieh, Ching-Cheng Wang, Po-Shiuan Hsieh, Teh-Ying Chou, Guochuan Emil Tsai
Summary: Pentarlandir UPPTA, a pure and potent tannic acid, exhibits activity against SARS-CoV-2 and HCoV-OC43 by inhibiting viral replication through 3CLpro. It shows high antiviral efficacy against SARS-CoV-2 and distributes well in lung tissue. Toxicology studies reveal its overall safety. Therefore, Pentarlandir UPPTA is considered a safe and efficacious pancoronal antiviral drug candidate.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.