Article
Immunology
Zhenjie Cao, Xin Yang, Tao Li, Zhiru Liu, Pengfei Li, Yongcan Zhou, Yun Sun
Summary: TroBcl2, an anti-apoptotic regulator, was cloned and its role in apoptosis was investigated in this study. It was found that TroBcl2 was widely distributed in various tissues and its expression was upregulated after LPS stimulation. Functional experiments demonstrated that TroBcl2 inhibits apoptosis by reducing mitochondrial membrane potential loss, decreasing DNA fragmentation, preventing cytochrome c release into the cytoplasm, and reducing caspase 3 and caspase 9 activations.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Manon Lernoux, Michael Schnekenburger, Mario Dicato, Marc Diederich
Summary: Multiple myeloma is a biologically complex hematological disorder that is currently incurable. Survival of MM molecular subgroups depends on the expression profiles of specific subsets of anti-apoptotic BCL-2 family members. The use of BCL-2 family protein inhibitors as potential treatments represents a strong rationale for further clinical investigation in MM therapy.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Syahru Agung Setiawan, Winston Zhenhao Liu, Pei-Wei Weng, Chia-Hwa Lee, Vijesh Kumar Yadav, Mardiah Suci Hardianti, Tsu-Yi Chao, Chi-Tai Yeh
Summary: In this study, the synergistic effects of the second generation BTK inhibitor zanubrutinib and the BCL-2 inhibitor navitoclax in suppressing Double-hit lymphoma (DHL) were demonstrated. Comprehensive in silico analysis from single-cell to bulk-level profiling validated the combination's ability to induce apoptosis and ferroptosis, effectively inhibiting DHL cell proliferation. Mechanistically, the combination disrupted NRF2 and HMOX1 while deactivating GPX4, triggering ferroptosis. In vivo studies showed that the combination of zanubrutinib and navitoclax effectively suppressed tumor growth.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Clemens Holz, Sandra Lange, Anett Sekora, Gudrun Knuebel, Saskia Krohn, Hugo Murua Escobar, Christian Junghanss, Anna Richter
Summary: Numerous hematologic neoplasms, including acute B-lymphoblastic leukemia (B-ALL), are characterized by overexpression of anti-apoptotic BCL-2 family proteins. Recent data indicated that combined BCL-2 and PI3K/AKT inhibition has synergistic anti-proliferative effects on B-ALL cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Hilmar Quentmeier, Robert Geffers, Vivien Hauer, Stefan Nagel, Claudia Pommerenke, Cord C. Uphoff, Margarete Zaborski, Hans G. Drexler
Summary: Overexpression of antiapoptotic BCL2 family proteins occurs in various hematologic malignancies and contributes to tumorigenesis by inhibiting the apoptotic machinery of the cells. The BH3 mimetics provide an option for medication, with venetoclax being the first drug applied for chronic lymphocytic leukemia and acute myeloid leukemia. The expression screening of cell lines using the LL-100 panel revealed that anaplastic large cell lymphoma (ALCL) and primary effusion lymphoma (PEL) showed high expression of MCL1 and low expression of BCL2. The MCL1 inhibitor AZD-5991 induced apoptosis in cell lines from both malignancies, suggesting its potential as a drug for these diseases. ALCL cell lines also expressed BCLXL and BCL2A1, contributing to cell survival. The combination of specific BH3 mimetics yielded synergistic effects, providing a novel strategy for the treatment of ALCL. The PI3K/mTOR inhibitor BEZ-235 could also be used in combination with AZD-5991, offering an alternative to avoid thrombocytopenia associated with BCLXL inhibitors.
SCIENTIFIC REPORTS
(2022)
Article
Virology
Giovana Biezus, Thierry Grima de Cristo, Gabriela Bassi das Neves, Mariana da Silva Casa, Paula Barros Brizola, Marina Silvestre Sombrio, Luiz Claudio Miletti, Renata Assis Casagrande
Summary: Only a few studies have investigated the impact of FeLV subgroups on disease development in spontaneously infected cats. This study identified FeLV-A and FeLV-B subgroups in cats with lymphoma and leukemia and examined the phylogenetic relationships of env sequences. The prevalence of FeLV-AB in cats with lymphoma and leukemia in Brazil highlights the genetic diversity involved in the pathogenesis of these neoplasms.
Article
Critical Care Medicine
Hansen Deng, Benjamin E. Zusman, Enyinna L. Nwachuku, John K. Yue, Yue-Fang Chang, Yvette P. Conley, David O. Okonkwo, Ava M. Puccio
Summary: Research indicates that variations in the Bcl-2 gene can affect intracranial pressure and prognosis of severe traumatic brain injury patients, with the GG genotype being associated with higher ICP, cerebral edema, and the need for surgical intervention.
JOURNAL OF NEUROTRAUMA
(2021)
Article
Pharmacology & Pharmacy
Hong Zhang, Zongwei Guo, Yafei Guo, Ziqian Wang, Yao Tang, Ting Song, Zhichao Zhang
Summary: The research showed that the transfer of Bim between Bcl-2-like protein and Hsp70 underlies the crosstalk in mitochondrial apoptosis pathway, leading to apoptosis in cancer cell lines by inhibiting free Bim and facilitating oncogenic client AKT folding and activation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Nanoscience & Nanotechnology
Fei Gao, Hualin Lan, Longbing Jiao, Tiantian Zuo, Nan Sun, Zebin Hu, Jie Huang
Summary: Lung cancer, despite advancements in etiology and treatments, still has poor survival rates. Nanoparticles (NPs) show promise as a tool for improving outcomes in drug treatment. This study evaluated the efficacy of combining NPs and Obatoclax mesylate (OM) on tumors, with results showing that OM-NPs effectively inhibit lung cancer cell proliferation and tumor growth, demonstrating the potential of NPs in targeted therapy.
Review
Biochemistry & Molecular Biology
Manzar Alam, Sabeeha Ali, Taj Mohammad, Gulam Mustafa Hasan, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan
Summary: Defects in apoptosis mechanism can enhance cancer cell growth and survival. Bcl-2, as an important anti-apoptotic molecule, is over-expressed in various cancers and has become a target for novel anti-tumor treatments. BH3-mimetics are emerging as promising compounds for cancer therapy, with ongoing clinical trials targeting Bcl-2 for multiple cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Haopeng Xu, Yi Xia, Juan Qin, Jie Xu, Chongyan Li, Yan Wang
Summary: The study demonstrated that LIPUS can improve POF induced by VCD by promoting follicular development, increasing sex hormone secretion, inhibiting excessive follicular atresia, and GCs apoptosis, possibly through increasing Bcl-2 protein expression and decreasing Bax expression in the ovaries.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2021)
Article
Medicine, Research & Experimental
Ya'an Kang, Jenying Deng, Jianhua Ling, Xinqun Li, Yi-Ju Chiang, Eugene J. Koay, Huamin Wang, Jared K. Burks, Paul J. Chiao, Mark W. Hurd, Manoop S. Bhutani, Jeffrey H. Lee, Brian R. Weston, Anirban Maitra, Naruhiko Ikoma, Ching-Wei D. Tzeng, Jeffrey E. Lee, Ronald A. DePinho, Robert A. Wolff, Shubham Pant, Florencia McAllister, Matthew H. G. Katz, Jason B. Fleming, Michael P. Kim
Summary: An organoid-based platform was developed to personalize PDAC therapy by quantifying PDO responses to drug treatments and evaluating tumor-stroma modulation.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Environmental Sciences
Jing Tang, Chenjuan Yao, Yingqi Liu, Jiaming Yuan, Li Wu, Kazuo Hosoi, Shali Yu, Chunyan Huang, Haiyan Wei, Gang Chen
Summary: In this study, it was elucidated that BCL-2, as a pro-apoptotic factor, plays a role in As2O3-induced apoptosis in BEAS-2B cells through NF-kappa B and p38 MAPK signaling pathways. The upregulation, nuclear localization, and phosphorylation of BCL-2 during apoptosis were found to be crucial factors in As2O3-induced cell death.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Review
Pharmacology & Pharmacy
Alakananda Basu
Summary: The interplay between apoptosis and senescence is crucial in cancer development, and targeting the Bcl-2 family proteins could be a promising strategy for cancer therapy. Therapy-induced senescence (TIS), induced by chemotherapeutic agents, has been controversial in its effect on therapeutic outcome. Clearance of senescent cells and overcoming their pro-survival mechanisms are important challenges in cancer treatment. This review article discusses recent literature on the role of the Bcl-2 family proteins in apoptosis and senescence, and the progress and limitations in targeting them for cancer therapy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Cell Biology
Laura M. Szczesniak, Caden G. Bonzerato, Richard J. H. Wojcikiewicz
Summary: The study revealed the interactome of Bok with various proteins, particularly those related to mitochondrial fission and cellular structures. It also identified novel physical and functional interactions between Bok and Mcl-1.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)