Article
Biochemistry & Molecular Biology
Masoud Mohammad Mirzapour, Majid Farshdousti Hagh, Faroogh Marofi, Saeed Solali, Arsalan Alaei
Summary: T-cell acute lymphoblastic leukemia is difficult to treat due to its fast progression and high complications. However, this study found that using the HDAC inhibitor SAHA can increase the sensitivity of leukemia cells to TRAIL-induced apoptosis, which may be a strategy to overcome TRAIL resistance in leukemic patients.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Christian Holmgren, Ellen Sunstrom Thornberg, Victoria Granqvist, Christer Larsson
Summary: This study reveals the molecular mechanisms of apoptosis induction by the combination therapy of Smac mimetics and TNF-related apoptosis-inducing ligand (TRAIL) in breast cancer cells. The results demonstrate that the combination treatment bypasses the c-FLIP-mediated inhibition of caspase activation through the formation of a complex including RIP1 and caspase-8.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Poulami Tapadar, Ambika Pal, Nirajan Ghosal, Bhupender Kumar, Tamalika Paul, Nabendu Biswas, Ranjana Pal
Summary: The purpose of this study was to identify key factors regulating TRAIL resistance in breast cancer. CDH1 was identified as a candidate hub gene, and its overexpression increased apoptosis in TR cells after rhTRAIL treatment. Analysis of patient data also showed low CDH1 mRNA levels in the TRAIL resistant group compared to the TRAIL sensitive group.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Oncology
Liqin Wang, Haojie Jin, Fleur Jochems, Siying Wang, Cor Lieftink, Isabel Mora Martinez, Giulia De Conti, Finn Edwards, Rodrigo Leite de Oliveira, Arnout Schepers, Yangyang Zhou, Jiaojiao Zheng, Wei Wu, Xingling Zheng, Shengxian Yuan, Jing Ling, Kathy Jastrzebski, Matheus Dos Santos Dias, Ji-Ying Song, Patrick N. H. Celie, Hideo Yagita, Ming Yao, Weiping Zhou, Roderick L. Beijersbergen, Wenxin Qin, Rene Bernards
Summary: Senolytics are drugs that kill senescent cells, and this study identifies cFLIP as a common vulnerability of senescent cancer cells. Activation of DR5 signaling can lead to efficient killing of senescent cancer cells and non-senescent cells can be sensitized to DR5 agonist through a bystander effect mediated by secretion of cytokines. Animal models confirm the effectiveness of combining pro-senescence therapy with DR5 activation.
Article
Cell Biology
Oliver H. Voss, Daniel Arango, Justin C. Tossey, Miguel A. Villalona Calero, Andrea Doseff
Summary: Apigenin sensitizes primary lung cancer cells to TRAIL-induced apoptosis through reprogramming alternative splicing of key TRAIL/DISC components and directly binding heat shock protein 70 to promote cell death. These findings emphasize the synergies between diet and cancer treatments, providing new avenues for improved cancer therapies.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Ya-Han Liang, Jiann-Ming Wu, Jui-Wen Teng, Eric Hung, Hwai-Shi Wang
Summary: Breast cancer is the leading cause of cancer-related death for women. Targeted therapy, such as TRAIL, shows potential in inducing apoptosis in cancer cells while mesenchymal stem cells can enhance TRAIL expression. The combination of TRAIL and cFLIP downregulation by embelin may provide a new therapeutic strategy for breast cancer.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Manami Semba, Shinji Takamatsu, Sachiko Komazawa-Sakon, Eiji Miyoshi, Chiharu Nishiyama, Hiroyasu Nakano, Kenta Moriwaki
Summary: The study identified proscillaridin A as a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics, particularly in colon cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Neil Kuehnle, Scout Mask Osborne, Ziyan Liang, Mark Manzano, Eva Gottwein
Summary: KSHV infection causes PEL. Human or viral cFLIP and MC159L can effectively rescue the loss of endogenous cFLIP activity in PEL cells. However, KSHV vFLIP is unable to fully rescue the loss of endogenous cFLIP and is functionally distinct.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Oncology
Andrea Rizzo, Alessandro Satta, Giulia Garrone, Adalberto Cavalleri, Alessandra Napoli, Francesco Raspagliesi, Mariangela Figini, Loris De Cecco, Egidio Iorio, Antonella Tomassetti, Delia Mezzanzanica, Marina Bagnoli
Summary: The study showed that down-regulation of CHKA can enhance the sensitivity of OC cells to TRAIL-mediated apoptosis, resulting in increased expression of TRC and TRAIL-R2, regulation of TRAIL-R2 localization, and enhanced TRAIL-induced apoptotic signaling.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
K. M. A. Zinnah, Sang-Youel Park
Summary: The study demonstrated the mechanism behind the synergistic anticancer effect of amitriptyline and TRAIL, showing that amitriptyline increases TRAIL-induced apoptosis by upregulating death receptors DR4 and DR5. Inhibition of autophagy by amitriptyline was also shown to enhance DR4 and DR5 expression.
Article
Biochemistry & Molecular Biology
Tomoya Fukuoka, Kenta Moriwaki, Shinji Takamatsu, Jumpei Kondo, Miki Tanaka-Okamoto, Azusa Tomioka, Manami Semba, Sachiko Komazawa-Sakon, Yoshihiro Kamada, Hiroyuki Kaji, Yasuhide Miyamoto, Masahiro Inoue, Kazuhiko Bessho, Yoko Miyoshi, Keiichi Ozono, Hiroyasu Nakano, Eiji Miyoshi
Summary: The study reveals that Lewis glycans positively regulate TRAIL-induced cell death, providing important insights into TRAIL sensitivity. Moreover, the expression of type I Lewis glycans is positively correlated with TRAIL sensitivity in colon cancer cell lines and patient-derived cancer organoids.
Article
Oncology
Gopikrishna Moku, Swathi Vangala, Venu Yakati, Chaitanya C. Gali, Soumen Saha, Vijay S. Madamsetty, Amber Vyas
Summary: This study investigated a novel series of SAHA analogs as potential chemotherapeutic agents for breast cancer treatment. The analogs displayed significant cytotoxic potential against cancer cell lines while being non-toxic to healthy cells, indicating tumor selectivity. Furthermore, the analogs demonstrated HDAC inhibition and induced apoptosis, making them potential candidates for breast cancer therapy.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Weiqiang Zhou, Han Han, Junnan Xu, Tao Sun, Xiuyan Feng
Summary: The combination of Chidamide and TRAIL has been shown to effectively induce breast cancer cell death while reducing the concentration of Chidamide. Additionally, the combination treatment also inhibits breast cancer tumor growth and is correlated with the expression of related apoptosis and autophagy factors.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Biotechnology & Applied Microbiology
Qiang Zhou, Jianxia Yuan, Yi Liu, Yayun Wu
Summary: Cisatracurium besilate inhibits gastric cancer cell proliferation, promotes apoptosis, increases the expression of p53 and PUMA, and enhances TRAIL-induced apoptosis. However, pifithrin-alpha can reverse the synergistic effects of cisatracurium besilate and TRAIL on AGS cell activities.
Article
Cell Biology
Kay Hanggi, Lazaros Vasilikos, Aida Freire Valls, Rosario Yerbes, Janin Knop, Lisanne M. Spilgies, Kristy Rieck, Tvisha Misra, John Bertin, Peter J. Gough, Thomas Schmidt, Carmen Ruiz de Almodovar, W. Wei-Lynn Wong
CELL DEATH & DISEASE
(2017)
Article
Oncology
Rosa Martin-Perez, Rosario Yerbes, Rocio Mora-Molina, Ana Cano-Gonzalez, Joaquin Arribas, Massimiliano Mazzone, Abelardo Lopez-Rivas, Carmen Palacios
Article
Cell Biology
Ana Cano-Gonzalez, Marta Mauro-Lizcano, Daniel Iglesias-Serret, Joan Gil, Abelardo Lopez-Rivas
CELL DEATH & DISEASE
(2018)
Article
Cell Biology
Marta Mauro-Lizcano, Abelardo Lopez-Rivas
CELL DEATH & DISEASE
(2018)
Article
Cell Biology
Carlos A. Elena-Real, Antonio Diaz-Quintana, Katiuska Gonzalez-Arzola, Adrian Velazquez-Campoy, Mar Orzaez, Abelardo Lopez-Rivas, Sergio Gil-Caballero, Miguel A. De la Rosa, Irene Diaz-Moreno
CELL DEATH & DISEASE
(2018)
Article
Cell Biology
Santiago Serrano-Saenz, Carmen Palacios, Daniel Delgado-Bellido, Laura Lopez-Jimenez, Angel Garcia-Diaz, Yolanda Soto-Serrano, J. Ignacio Casal, Ruben A. Bartolome, Jose Luis Fernandez-Luna, Abelardo Lopez-Rivas, F. Javier Oliver
CELL DEATH & DISEASE
(2019)
Article
Medicine, Research & Experimental
Nathalie Tisch, Aida Freire-Valls, Rosario Yerbes, Isidora Paredes, Silvia La Porta, Xiaohong Wang, Rosa Martin-Perez, Laura Castro, Wendy Wei-Lynn Wong, Leigh Coultas, Boris Strilic, Hermann-Josef Grone, Thomas Hielscher, Carolin Mogler, Ralf H. Adams, Peter Heiduschka, Lena Claesson-Welsh, Massimiliano Mazzone, Abelardo Lopez-Rivas, Thomas Schmidt, Hellmut G. Augustin, Carmen Ruiz de Almodovar
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Cell Biology
Rocio Mora-Molina, Daniela Stoehr, Markus Rehm, Abelardo Lopez-Rivas
Summary: Protein misfolding or unfolding and the resulting endoplasmic reticulum stress commonly occur in highly proliferative tumors. The role of caspase-8 inhibitor cFLIP in regulating the balance between apoptosis and survival in colon cancer cells undergoing ER stress has been investigated. Maintaining high cFLIP levels during ER stress can inhibit caspase-8 activation and apoptosis, while cFLIP knockdown accelerates caspase-8 activation and apoptosis during ER stress. The resistance of multicellular tumor spheroids to ER stress-induced apoptosis correlates with sustained cFLIP(L) expression.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Rocio Mora-Molina, Abelardo Lopez-Rivas
Summary: This review article discusses the molecular mechanisms regulating cell fate decisions in tumor cells undergoing ER stress, with a focus on the role of TRAIL-R2/DR5 in the apoptotic process and the mechanisms controlling FLIP levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elena Gomez-Marin, Melanija Posavec-Marjanovic, Laura Zarzuela, Laura Basurto-Cayuela, Jose A. Guerrero-Martinez, Gonzalo Arribas, Rosario Yerbes, Maria Ceballos-Chavez, Manuel Rodriguez-Paredes, Mercedes Tome, Raul Duran, Marcus Buschbeck, Jose C. Reyes
Summary: The study reveals that PHF14 and HMG20A cooperate in regulating pathways involved in epithelial-mesenchymal plasticity, impacting cell migration, invasion, and cell-cell adhesion abilities. The PHF14-HMG20A complex modulates the Hippo pathway through direct interaction with the TEAD1 transcription factor.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Rosario Yerbes, Rocio Mora-Molina, F. Javier Fernandez-Farran, Laura Hiraldo, Abelardo Lopez-Rivas, Carmen Palacios
Summary: This study reveals a previously unknown cell death mechanism triggered in glutamine-addicted tumor cells in response to glutamine metabolism limitation. The mechanism is regulated by GCN2 activation induced by glutamine starvation and involves the activation of the extrinsic apoptotic pathway mediated by TRAIL-R2.
CELL DEATH & DISEASE
(2022)
Letter
Biochemistry & Molecular Biology
Cristina Munoz-Pinedo, Abelardo Lopez-Rivas
CELL DEATH AND DIFFERENTIATION
(2018)
Meeting Abstract
Biophysics
M. A. de la Rosa, K. Gonzalez-Arzola, F. Rivero-Rodriguez, A. J. Diaz-Quintana, A. Cano-Gonzalez, A. Velazquez-Campoy, A. Lopez-Rivas, I. Diaz-Moreno
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2017)