Article
Biochemistry & Molecular Biology
Yong-Hwi Kang, Jin-Seok Lee, Nam-Hun Lee, Seung-Hyung Kim, Chang-Seob Seo, Chang-Gue Son
Summary: Colorectal cancer (CRC) is the third most common cancer worldwide among both men and women, with early detection and resection being the best treatment and chemotherapy a main treatment option. Coptidis Rhizoma extract (CRE) shows potential as an adjuvant agent against 5-FU-resistant colorectal cancers by reducing cell viability and inhibiting thymidylate synthase (TS) expression.
Article
Biochemistry & Molecular Biology
Chinatsu Kurasaka, Yoko Ogino, Akira Sato
Summary: This study identified that 5-FU-resistant cells exhibit increased TS expression and utilize the TS enzyme to trap the active metabolite FdUMP, resulting in resistance to 5-FU and its analogs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Denis Mteremko, Daniel M. Shadrack, Fidele Ntie-Kang, Jaffu Chilongola, Musa Chacha
Summary: 5-fluorouracil and analogs are commonly used in chemotherapy for solid tumors, but resistance and toxicity are common. Repurposing FDA drugs targeting human thymidylate synthase identified several drugs with potential for further development in cancer treatment. The study prioritized four FDA drugs (Erismodegib, Irinotecan, Conivaptan, and Ergotamine) for validation. The role of water in drug interactions and its contribution to binding energy was also explored.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cell Biology
Erica Pranzini, Elisa Pardella, Livio Muccillo, Angela Leo, Ilaria Nesi, Alice Santi, Matteo Parri, Tong Zhang, Alejandro Huerta Uribe, Tiziano Lottini, Lina Sabatino, Anna Caselli, Annarosa Arcangeli, Giovanni Raugei, Vittorio Colantuoni, Paolo Cirri, Oliver D. K. Maddocks, Paola Chiarugi, Paolo Paoli, Maria Letizia Taddei
Summary: The study reveals that alterations in serine metabolism affect the sensitivity of colorectal cancer cells to 5-FU. Resistant cells become dependent on serine by increasing its synthesis or uptake. Mitochondrial compartmentalization of one-carbon metabolism supports purine biosynthesis and DNA damage response in resistant cells.
Article
Oncology
Gulam Mohmad Rather, Michael Anyanwu, Tamara Minko, Olga Garbuzenko, Zoltan Szekely, Joseph R. Bertino
Summary: The E2F family of transcription factors plays a crucial role in cell proliferation, differentiation, and DNA repair, and their dysregulation in cancer can be targeted for antitumor therapy. Combining a peptide targeting E2F transcription with chemotherapy drugs like cisplatin or pemetrexed has shown enhanced antitumor activity, especially in lung adenocarcinoma.
Article
Biochemistry & Molecular Biology
Changwon Yang, Jisoo Song, Sunwoo Park, Jiyeon Ham, Wonhyoung Park, Hahyun Park, Garam An, Taeyeon Hong, Hee Seung Kim, Gwonhwa Song, Whasun Lim
Summary: This study investigated the effects of quercetin on colorectal cancer cells and found that quercetin can suppress thymidylate synthase levels and induce oxidative stress and calcium dysregulation. It also regulates the expression of specific tiRNAs and enhances apoptosis in CRC cells. Quercetin treatment in colitis-associated CRC mice showed enhanced sensitivity to 5-FU and reduced tumor growth. These findings suggest that quercetin has the potential to be used as an adjuvant with 5-FU for the treatment of CRC.
Article
Biochemistry & Molecular Biology
Sareh Kamran, Ajantha Sinniah, Zamri Chik, Mohammed Abdullah Alshawsh
Summary: The combination of 5-FU and diosmetin has a synergistic effect against colorectal cancer cells, reducing the toxicity of 5-FU while enhancing its anticancer efficacy. This combination induces apoptosis and interrupts cell mitosis to achieve its anticancer effects.
Article
Biochemistry & Molecular Biology
Changwon Yang, Jisoo Song, Sunjae Hwang, Jungil Choi, Gwonhwa Song, Whasun Lim
Summary: The study found that apigenin enhances the inhibitory effect of 5-FU on colorectal cancer cells by suppressing TS expression, promoting apoptosis, and disrupting the cell cycle. Additionally, apigenin increases reactive oxygen species production and intracellular calcium levels, indicating its potential to improve therapeutic efficacy.
Article
Oncology
Marie Malier, Khaldoun Gharzeddine, Marie-Helene Laverriere, Sabrina Marsili, Fabienne Thomas, Thomas Decaens, Gael Roth, Arnaud Millet
Summary: The study reveals that macrophages specifically overexpress DPD in hypoxia, leading to macrophage-induced chemoresistance to 5-FU, while tumor cells do not express significant levels of DPD. These findings shed light on the crucial role of TAMs in promoting chemoresistance in colorectal cancers.
Article
Chemistry, Medicinal
Madhuri Dasari, Stephen C. Pelly, Jiafeng Geng, Hannah B. Gold, Nicole Pribut, Savita K. Sharma, Michael P. D'Erasmo, Perry W. Bartsch, Carrie Sun, Kiran Toti, Rebecca S. Arnold, John A. Petros, Lingjie Xu, Yi Jiang, Dennis C. Liotta, Eric J. Miller
Summary: 5-Fluorouracil and its derivatives have been used for cancer treatment for many years. However, they can cause unwanted systemic toxicity due to unfavorable metabolic events. In this study, we designed and synthesized 5'-substituted analogs of FdUMP to inhibit thymidylate synthase while preventing undesirable metabolism. Computational calculations and pharmacological assessments demonstrated that these analogs maintain the potency of thymidylate synthase inhibition.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Vipul Panchal, Sushil Kumar, Shaikh Nausad Hossain, Dileep Vasudevan
Summary: This study presents the first thymidylate synthase (TS) structure from a crustacean virus, highlighting its distinction from shrimp and other TS structures, providing important insights for further research.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Cell Biology
Alireza Mafi, Malihe Rezaee, Neda Hedayati, Sara Diana Hogan, Russel J. Reiter, Mohammad-Hossein Aarabi, Zatollah Asemi
Summary: Combined chemotherapy is an effective treatment for cancer patients, as it combines multiple therapeutic agents to target different aspects of cancer. 5-FU is a widely used chemotherapy agent, while melatonin has shown anti-cancer properties. This review aims to evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy and identify their common signaling pathways.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biology
Marlies C. Ludikhuize, Sira Gevers, Nguyen T. B. Nguyen, Maaike Meerlo, S. Khadijeh Shafiei Roudbari, M. Can Gulersonmez, Edwin C. A. Stigter, Jarno Drost, Hans Clevers, Boudewijn M. T. Burgering, Maria J. Rodriguez Colman
Summary: In p53-deficient colorectal cancer organoids, 5-fluorouracil induces pyrimidine imbalance, which leads to DNA damage and cell death. Rewiring glucose metabolism through PDK inhibition by DCA enhances 5-FU toxicity in glycolytic p53-deficient organoids. This has important implications for improving chemotherapy strategies for colorectal cancer, and p53 emerges as a key factor in determining the response to 5-FU.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Chun-Liang Tung, Jyh-Cheng Chen, Jen-Chung Ko, Li-Ling Liu, Chin-Cheng Chien, I-Hsiang Huang, Yong-Cing Tsao, Hsiang-Hung Cheng, Tzu-Ying Chen, Ting-Chuan Yen, Yun-Wei Lin
Summary: The study showed that capsaicin in combination with 5-FU exhibits synergistic anticancer effects on NSCLC cells by downregulating TS expression and inhibiting cell growth through p38 MAPK inactivation.
NATURAL PRODUCT COMMUNICATIONS
(2021)
Article
Oncology
Nair Hariprasad Haritha, Akbar Nawab, Vinod Vijayakurup, Nikhil Ponnoor Anto, Vijayasteltar B. Liju, Vijai V. Alex, Areekkara Nisthul Amrutha, Sreekumar U. Aiswarya, Mundanattu Swetha, Balachandran S. Vinod, Sankar Sundaram, Maria Guijarro, Thomas Herlevich, Archana Krishna, Nesteena K. Nestory, Smitha Bava, Chittalakkottu Sadasivan, Maria Zajac-Kaye, Ruby John Anto
Summary: A study found that curcumin enhances the sensitivity of breast cancer cells to 5-fluorouracil chemotherapy, particularly in triple-negative breast cancer, providing a new strategy for the treatment of breast cancer.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Bhaskar Bhattacharya, Mohd Feroz Mohd Omar, Richie Soong
BRITISH JOURNAL OF PHARMACOLOGY
(2016)
Article
Oncology
Bhaskar Bhattacharya, Sarah Hong Hui Low, Mei Ling Chong, Dilys Chia, King Xin Koh, Nur Sabrina Sapari, Stanley Kaye, Huynh Hung, Touati Benoukraf, Richie Soong
Article
Oncology
King Xin Koh, Gim Hwa Tan, Sarah Hong Hui Low, Mohd Feroz Mohd Omar, Min Ji Han, Barry Iacopetta, Ross Soo, Mounia Beloueche-Babari, Bhaskar Bhattacharya, Richie Soong
Article
Gastroenterology & Hepatology
Marie Loh, Natalia Liem, Aparna Vaithilingam, Pei Li Lim, Nur Sabrina Sapari, Eiram Elahi, Zuan Yu Mok, Chee Leong Cheng, Benedict Yan, Brendan Pang, Manuel Salto-Tellez, Wei Peng Yong, Barry Iacopetta, Richie Soong
BMC GASTROENTEROLOGY
(2014)
Article
Pharmacology & Pharmacy
B. Bhattacharya, S. H. H. Low, C. Soh, N. Kamal Mustapa, M. Beloueche-Babari, K. X. Koh, J. Loh, R. Soong
BRITISH JOURNAL OF PHARMACOLOGY
(2014)
Article
Oncology
CheeKian Tham, MinHoe Chew, Richie Soong, JitFong Lim, MeiKim Ang, ChoongLeong Tang, Yi Zhao, Simon Y. K. Ong, Yanqun Liu
Article
Oncology
Yuan-Yuan Wen, Xiong-Fei Pan, Marie Loh, Shu-Juan Yang, Yao Xie, Zhi Tian, He Huang, Hui Lan, Feng Chen, Richie Soong, Chun-Xia Yang
EUROPEAN JOURNAL OF CANCER PREVENTION
(2014)
Article
Gastroenterology & Hepatology
Ada Collura, Anais Lagrange, Magali Svrcek, Laetitia Marisa, Olivier Buhard, Agathe Guilloux, Kristell Wanherdrick, Coralie Dorard, Anna Taieb, Arnaud Saget, Marie Loh, Richie Soong, Nikolajs Zeps, Cameron Platell, Andrew Mews, Barry Iacopetta, Aurelie De Thonel, Renaud Seigneuric, Guillaume Marcion, Caroline Chapusot, Come Lepage, Anne-Marie Bouvier, Marie-Pierre Gaub, Gerard Milano, Janick Selves, Patrick Senet, Patrice Delarue, Hayat Arzouk, Claire Lacoste, Arnaud Coquelle, Leila Bengrine-Lefevre, Christophe Tournigand, Jeremie H. Lefevre, Yann Parc, Denis S. Biard, Jean-Francois Flejou, Carmen Garrido, Alex Duval
Article
Pharmacology & Pharmacy
Kok-Yong Seng, Kim-Hor Hee, Gaik Hong Soon, Nur Sabrina Sapari, Richie Soong, Boon-Cher Goh, Lawrence Soon-U Lee
JOURNAL OF CLINICAL PHARMACOLOGY
(2014)
Review
Oncology
Naresh Kumar, Yongsheng Chen, Aye S. Zaw, Deepti Nayak, Qasim Ahmed, Richie Soong, Hee K. Wong
Review
Oncology
Raghav Sundar, Richie Soong, Byoung-Chul Cho, Julie R. Brahmer, Ross A. Soo
Article
Biochemistry & Molecular Biology
Manish Mani Subramaniam, Marie Loh, Jason Yongsheng Chan, Natalia Liem, Pei Li Lim, Yong Wei Peng, Xn Yii Lim, Khay Guan Yeoh, Barry Iacopetta, Richie Soong, Manuel Salto-Tellez
MOLECULAR CARCINOGENESIS
(2014)
Article
Genetics & Heredity
Emilie A. Bard-Chapeau, Anh-Tuan Nguyen, Alistair G. Rust, Ahmed Sayadi, Philip Lee, Belinda Q. Chua, Lee-Sun New, Johann de Jong, Jerrold M. Ward, Christopher K. Y. Chin, Valerie Chew, Han Chong Toh, Jean-Pierre Abastado, Touati Benoukraf, Richie Soong, Frederic A. Bard, Adam J. Dupuy, Randy L. Johnson, George K. Radda, Eric Chun Yong Chan, Lodewyk F. A. Wessels, David J. Adams, Nancy A. Jenkins, Neal G. Copeland
Article
Cell & Tissue Engineering
Jin Rong Ow, Hui Ma, Angela Jean, Ziyi Goh, Yun Hwa Lee, Yew Mei Chong, Richie Soong, Xin-Yuan Fu, Henry Yang, Qiang Wu
STEM CELLS AND DEVELOPMENT
(2014)