Article
Cell Biology
Violetta Ritter, Franziska Krautter, Diana Klein, Verena Jendrossek, Justine Rudner
Summary: Hypoxia is a major obstacle to successful radiotherapy for solid tumors. Exposure to acute and adaptation to chronic cycling hypoxia alters Bcl-2 family proteins, leading to increased resistance to apoptosis and decreased radiotherapy success. Targeting the Bcl-2 rheostat with ABT-263 shows promise in overcoming radioresistance of cancer cells exposed to hypoxia.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Maria Josefina Quezada, Maria Elisa Picco, Maria Belen Villanueva, Maria Victoria Castro, Gaston Barbero, Natalia Brenda Fernandez, Edith Illescas, Pablo Lopez-Bergami
Summary: BCL2L10, a less studied protein from the Bcl-2 anti-apoptotic protein group, is abundantly and frequently expressed in melanoma cells and tumor samples, driven by STAT3-mediated transcription. It acts as a pro-survival factor by protecting cells from the cytotoxic effects of various drugs and inhibitors, suggesting that targeting BCL2L10 may enhance the clinical efficacy of other therapies for malignant melanoma.
Article
Biochemistry & Molecular Biology
Wonseon Ryu, Chul-Woo Park, Junghoon Kim, Hyungwoo Lee, Hyewon Chung
Summary: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and current treatments are invasive and carry the risk of infection. The pathogenic mechanism of AMD involves a combination of genetic predisposition and cellular senescence. Senolytic drugs, such as ABT-263, selectively eliminate senescent cells and have the potential to be a new treatment for AMD by targeting senescent retinal pigment epithelium (RPE) cells. Our study showed that ABT-263 can kill senescent ARPE-19 cells and alleviate retinal degeneration in a mouse model, suggesting it may be the first orally administered senolytic drug for AMD.
MOLECULES AND CELLS
(2023)
Article
Biochemistry & Molecular Biology
Petra Gorombei, Fabien Guidez, Saravanan Ganesan, Mathieu Chiquet, Andrea Pellagatti, Laure Goursaud, Nilgun Tekin, Stephanie Beurlet, Satyananda Patel, Laura Guerenne, Carole Le Pogam, Niclas Setterblad, Pierre de la Grange, Christophe LeBoeuf, Anne Janin, Maria-Elena Noguera, Laure Sarda-Mantel, Pascale Merlet, Jacqueline Boultwood, Marina Konopleva, Michael Andreeff, Robert West, Marika Pla, Lionel Ades, Pierre Fenaux, Patricia Krief, Christine Chomienne, Nader Omidvar, Rose Ann Padua
Summary: The study demonstrates that the BCL-2 inhibitor ABT-737 significantly extends survival in the high-risk MDS mouse model and reduces bone marrow blasts and LSK cells, providing new insights into the treatment of MDS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nanoscience & Nanotechnology
Jiaming Zhang, Baofang Zhang, Congli Pu, Jiarui Cui, Kexin Huang, Hongbo Wang, Yingchao Zhao
Summary: A novel nanoliposomal DT2216 (DT@NPs) was developed for targeting Bcl-xL, which exhibited enhanced ability to degrade Bcl-xL and induce apoptosis in cervical and breast cancer cells compared to DT2216. In a mouse model, DT@NPs showed stronger inhibition of tumor growth. DT@NPs also had notable cytocompatibility in normal cells and good biodistribution in vivo.
ADVANCED COMPOSITES AND HYBRID MATERIALS
(2023)
Article
Oncology
Weiwei Li, Yiming Ma, Longmei He, Hongwei Li, Yi Chu, Zheng Jiang, Xinhua Zhao, Yongzhan Nie, Xishan Wang, Hongying Wang
Summary: The study revealed a positive association between the tumor protein Bcl-xL and protease-activated receptor 2 (PAR2) in colorectal carcinoma. Activation of PAR2 stabilizes Bcl-xL by altering RNF152 signaling, and inhibition of PAR2 increases colorectal cancer sensitivity to EGFR-targeted therapies.
Article
Cell Biology
Barbora Adamova, Kamila Rihova, Jana Pokludova, Petr Benes, Jan Smarda, Jarmila Navratilova
Summary: An acidic environment and hypoxia in cancer cells contribute to their resistance to therapy. The deregulation of the PI3K/Akt pathway is common in colon cancer. Combining Akt inhibitors with Bcl-2/Bcl-xL inhibitors could be an effective treatment strategy for colon cancer.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Nicolas Rosa, Femke Speelman-Rooms, Jan B. Parys, Geert Bultynck
Summary: Members of the Bcl-2 protein family play important roles in controlling apoptotic cell death. Beyond their well-known functions in the mitochondria, these proteins also modulate intracellular Ca2+ signals originating from the endoplasmic reticulum. Recent studies have revealed new insights into the functions and interactions of Bcl-2 and Bcl-xL, opening up new possibilities for the treatment of Bcl-xL-dependent cancers.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Chemistry, Medicinal
Mike-Andrew Westhoff, Marie Schuler-Ortoli, Daniela Zerrinius, Amina Hadzalic, Andrea Schuster, Hannah Strobel, Angelika Scheuerle, Tiana Wong, Christian Rainer Wirtz, Klaus-Michael Debatin, Aurelia Peraud
Summary: Medulloblastoma is a common solid tumor in children, and current treatments are not highly effective. Modulating the Bcl-2 family members could potentially improve the treatment outcomes by inhibiting tumor cells' resistance to apoptosis.
Article
Biochemistry & Molecular Biology
Yang Wang, Lin Zhang, Xiao-Lin Sun, Ya-Chun Lu, Si Chen, Dong-Sheng Pei, Lan-Sheng Zhang
Summary: The study found that NRP1 can enhance stem cell properties and confer radioresistance in breast cancer cells. Mechanistically, NRP1 decreases IR-induced apoptosis by downregulating Bcl-2. These findings provide potential therapeutic targets for improving the efficacy of radiotherapy in breast cancer.
Article
Biochemistry & Molecular Biology
Hao Li, Shuheng Dong, Lili Duan
Summary: The study compared the binding modes of Bcl-xL and Bcl-2 with ligands ABT-263/43b, finding that the Bcl-2 and ABT-263 system had stronger binding ability. The predicted hot spot residues and their energy distributions can guide the design of peptide and small-molecule drugs targeting Bcl-xL and Bcl-2.
JOURNAL OF MOLECULAR MODELING
(2021)
Article
Biochemistry & Molecular Biology
Sudjit Luanpitpong, Montira Janan, Juthamas Yosudjai, Jirarat Poohadsuan, Pithi Chanvorachote, Surapol Issaragrisil
Summary: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with poor prognosis due to drug resistance. Overexpression of antiapoptotic Bcl-xL and depletion of proapoptotic Bax contribute to acquired resistance to bortezomib (BTZ) in MCL cells. High Bcl-xL and low Bax levels are associated with poor prognosis in MCL patients. Targeting these proteins using BH3 mimetics and Bax activators may be a promising strategy to overcome drug resistance in MCL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Anna R. Michmerhuizen, Lynn M. Lerner, Connor Ward, Andrea M. Pesch, Amanda Zhang, Rachel Schwartz, Kari Wilder-Romans, Joel R. Eisner, James M. Rae, Lori J. Pierce, Corey W. Speers
Summary: The study investigated the radiosensitization effect of AR and ER inhibition in AR+/ER+ breast cancers. The results showed that AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer, while the efficacy of ER antagonists may depend on the expression of AR.
BRITISH JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Luxi Qian, Karin A. Vallega, Weilong Yao, Dongsheng Wang, Yifan Zhai, Xia He, Shi-Yong Sun
Summary: This study evaluated the therapeutic efficacy of the novel Bcl-2/Bcl-X-L dual inhibitor APG1252-M1 against non-small cell lung cancer (NSCLC) cells. The results showed that APG1252-M1 effectively decreased the survival of NSCLC cells with low levels of Mcl-1 and induced apoptosis. Furthermore, the combination of APG1252-M1 with osimertinib synergistically decreased the survival of EGFR-mutant NSCLC cells, including those resistant to osimertinib, and inhibited the growth of osimertinib-resistant tumors in vivo.
MOLECULAR CARCINOGENESIS
(2022)
Article
Biochemistry & Molecular Biology
Jean-Pierre Daguer, Arthur Gonse, Yevhenii Shchukin, Lluc Farrera-Soler, Sofia Barluenga, Nicolas Winssinger
Summary: A dual Bcl-X-L / Bcl-2 inhibitor was discovered from DNA-encoded libraries using a two-step process. The best compound showed comparable cellular activity to venetoclax, the first-in-class therapeutic targeting Bcl-2. Through a series of assays, the compound was found to have tight binding adducts with selective target engagement and high affinity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)