Article
Oncology
Michael Bordonaro
Summary: Dietary fiber has a preventive effect against colorectal cancer due to the fermentation product butyrate inducing CRC cell growth arrest and apoptosis. The interaction of CBP and p300 with beta-catenin influences CRC cell physiology, with CBP-Wnt vs. p300-Wnt activity ratio impacting the outcomes. Sam68 and Pygo2 are hypothesized to be responsible for the cell type-specific response of CRC cell lines to ICG-001 and butyrate cotreatment.
Article
Biochemistry & Molecular Biology
Jang-Hyun Choi, Tae-Young Jang, So-El Jeon, Jee-Heun Kim, Choong-Jae Lee, Hyeon-Ji Yun, Ji-Youn Jung, So-Yeon Park, Jeong-Seok Nam
Summary: Recurrence and metastasis are main challenges in CRC treatment, driven by a small subpopulation of cells called cancer stem-like cells (CSCs). Transcriptomic profiling showed upregulation of Wnt pathway and stemness genes in metastatic tumors, and treatment with small-molecule Wnt inhibitor ICG-001 effectively suppressed CSC behavior and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Angelique N. Masibag, Christopher J. Bergin, Joshua R. Haebe, Aicha Zouggar, Muhammad S. Shah, Tamara Sandouka, Amanda Mendes da Silva, Francois M. Desrochers, Aube Fournier-Morin, Yannick D. Benoit
Summary: Cancer stem cells play a key role in tumorigenesis and therapy resistance, and disrupting CBP/beta-Catenin interactions with reverse-turn peptidomimetics shows promise in curbing hyperactive Wnt/beta-Catenin signaling in CSCs. Recent studies have identified Sam68 as a critical mediator of the response to these peptidomimetics in CSC populations. Through in silico drug discovery, YB-0158 was identified as a small molecule with enhanced translational potential in altering key hallmarks of human colorectal CSCs.
Article
Oncology
Luo Chen, Yiu Chun Chiang, Lai Sheung Chan, Wai Yin Chau, Maria Li Lung, Michael Kahn, Kwok Wai Lo, Nai Ki Mak, Hong Lok Lung
Summary: Metastatic nasopharyngeal carcinoma (NPC) is an incurable disease and the main cause of NPC-related deaths. This study investigates the anti-metastatic activity of the CBP/beta-catenin Wnt antagonist, IGC-001, in NPC. The results show that ICG-001 treatment reduces the adhesion, migration, and invasion capabilities of NPC cells, which are closely associated with distant metastasis. MiR-134 is consistently upregulated by ICG-001 treatment and its overexpression inhibits cancer cell adhesion, migration, and invasion. Furthermore, miR-134 downregulates integrin beta 1 (ITGB1), a key factor in cell adhesion and migration. The study demonstrates that modulation of the Wnt signaling pathway by ICG-001 can effectively inhibit NPC metastasis through the miR-134/ITGB1 axis.
Article
Oncology
Souvick Roy, Yinghui Zhao, Yate-Ching Yuan, Ajay Goel
Summary: Colorectal cancer (CRC) is a common and deadly malignancy, with most patients experiencing relapse after surgery and 5FU-based chemotherapy. The presence of cancer stem-like cells (CSCs) is a contributing factor to therapy resistance and disease relapse. This study explores a new therapeutic strategy using metformin and ICG-001, a Wnt signaling inhibitor, to overcome CSC-mediated chemoresistance in CRC.
Article
Materials Science, Multidisciplinary
Fan Sheng, Yinli Luo, Di Wu, Jiachen Yuan, Ge Zheng, Yuhao Zheng, Zhehu Jin
Summary: This study investigates the effects of ICG-001 on the proliferation, invasion, and apoptosis of keloid fibroblasts, as well as the excessive deposition of collagen. It also explores the inhibitory effect of ICG-001 on tumor growth in a keloid mouse model. The results show that ICG-001 is effective in inhibiting keloid fibroblast proliferation and promoting apoptosis.
MATERIALS & DESIGN
(2022)
Article
Oncology
Zhaoyan Lin, Qingqing Li, Ying Zhao, Zixiang Lin, Nan Cheng, Di Zhang, Gang Liu, Jiahao Lin, Hong Zhang, Degui Lin
Summary: The combination therapy of AF and ICG-001 synergistically inhibits the growth and invasion of human colon cancer cells by inhibiting STAT3 phosphorylation and inducing apoptotic cell death. This combination also effectively suppresses the growth and metastasis of colon cancer in animal models, showing potential therapeutic properties for human colon cancer.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Karolina Kazmierczak-Siedlecka, Luigi Marano, Elvira Merola, Franco Roviello, Karol Polom
Summary: Accumulating evidence suggests that microbiota-derived metabolites, such as butyrate, play a significant role in tumor prevention and cancer treatment. Butyrate has a wide range of beneficial properties, including influencing the immune system, maintaining intestinal barrier integrity, and enhancing anti-cancer treatment efficiency. Sodium butyrate, as a potential option for colorectal cancer patients, can be obtained through food with special medical purposes.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ling Ma, Yu Lin, Shan-Wen Sun, Jun Xu, Ting Yu, Wen-Long Chen, Liang-Hui Zhang, Yu-Chen Guo, Yi-Wen Wang, Tao Chen, Ji-Fu Wei, Ling-Jun Zhu
Summary: The study showed that KIAA1429 was significantly upregulated in colorectal cancer tissues and its high expression was associated with shorter overall survival. KIAA1429 promoted colorectal cancer cell proliferation by negatively regulating WEE1 expression, indicating its potential as a prognostic marker for CRC.
Article
Cell Biology
I-Lun Hsin, Pei-Ju Wu, Sheau-Chung Tang, Chu-Chyn Ou, Hui-Yi Chang, Huang-Pin Shen, Jiunn-Liang Ko, Po-Hui Wang
Summary: ICG-001 inhibits endometrial cancer by reducing cell viability, cancer stem cell sphere formation, and cell cycle progression, while activating autophagy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Veterinary Sciences
Zhaoyan Lin, Zixiang Lin, Ying Zhao, Nan Cheng, Di Zhang, Jiahao Lin, Hong Zhang, Degui Lin
Summary: Canine breast cancer is the most common spontaneous tumor in intact female dogs, especially in developing countries. The combination of Auranofin and ICG-001 has been shown to synergistically suppress the growth of CBC by inducing apoptosis through mitochondrial signaling pathway and ROS production. This combination therapy may offer a novel potential choice for the clinical treatment of CBC.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ying He, Yuhang Ling, Zhiyong Zhang, Randall Tyler Mertens, Qian Cao, Xutao Xu, Ke Guo, Qian Shi, Xilin Zhang, Lixia Huo, Kan Wang, Huihui Guo, Weiyun Shen, Manlu Shen, Wenming Feng, Peng Xiao
Summary: Through metabolomics analysis, we found that butyrate concentrations were decreased in CRC patients, and supplementation of butyrate increased the sensitivity of CRC to ferroptosis induction, especially in cancer stem cells. Mechanistically, butyrate inhibited xCT expression and xCT-dependent glutathione synthesis, and induced c-Fos expression by disrupting class I HDAC activity. Furthermore, butyrate can enhance the pro-ferroptotic function of oxaliplatin.
Article
Oncology
Saira R. Ali, Ayla Orang, Shashikanth Marri, Ross A. McKinnon, Robyn Meech, Michael Z. Michael
Summary: High-fiber diets with butyrate can prevent colorectal cancer by modulating gene and microRNA expression, providing insights into potential novel drug targets for cancer prevention and treatment.
Article
Gastroenterology & Hepatology
Xing Kang, Changan Liu, Yanqiang Ding, Yunbi Ni, Fenfen Ji, Harry Cheuk Hay Lau, Lanping Jiang, Joseph J. Y. Sung, Sunny H. Wong, Jun Yu
Summary: This study found that the probiotic species R. intestinalis has a protective effect against colorectal tumourigenesis by producing butyrate, and it can also enhance the efficacy of anti-PD-1 treatment. These findings provide evidence for the potential use of R. intestinalis as an adjuvant therapy for colorectal cancer.
Review
Biochemistry & Molecular Biology
Cyrollah Disoma, Yuzheng Zhou, Shanni Li, Jian Peng, Zanxian Xia
Summary: The Wnt/β-catenin signaling pathway plays a crucial role in colorectal carcinogenesis, but no clinically approved therapies targeting this pathway currently exist. New modulators of the pathway are involved not only in cancer initiation but also in chemoresistance, epithelial-mesenchymal transition, and cancer stem cell renewal. CDX2 shows potential as a promising molecular target for colorectal cancer therapeutics, although further studies are needed to determine its significance. Overall, the regulation of the Wnt/β-catenin signaling pathway remains complex and not fully understood, posing a major barrier to the development of targeted chemotherapeutic agents.