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
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
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
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)
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
Chemistry, Medicinal
Michael J. Roy, Amelia Vom, Toru Okamoto, Brian J. Smith, Richard W. Birkinshaw, Hong Yang, Houda Abdo, Christine A. White, David Segal, David C. S. Huang, Jonathan B. Baell, Peter M. Colman, Peter E. Czabotar, Guillaume Lessene
Summary: The BCL-2 family of proteins is an important target for anticancer drug development, with inhibitors like ABT-199/vebetoclax showing transformative effects. Developing new validated chemical series for BCL-X-L is desirable.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
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, Physical
Jiasi Luan, Baichun Hu, Shizhun Wang, Haihan Liu, Shuaizhong Lu, Weixia Li, Xizhe Sun, Jiyue Shi, Jian Wang
Summary: The BCL-XL protein, a member of the anti-apoptotic subfamily of the BCL-2 protein family, is a promising target for anti-tumor drug research. This study investigated the selective mechanism of BCL-XL/2 inhibition using computational methods and identified the significant impact of specific residues on the inhibitory selectivity. These findings provide useful references for the rational design of BCL-XL/2 selective inhibitors with better affinity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Takuya Kikuchi, Akane Hayashi, Naohiro Ikeda, Osamu Morita, Junichi Tasaki
Summary: Green tea polyphenols, especially EGCG, have various beneficial effects on human health. This study investigated the metabolism and transport mechanisms of EGCG in the human small intestine, providing insights into the effects of green tea polyphenols.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Maria Gagliardi, Ana Tari Ashizawa
Summary: The Bcl-2 family plays a crucial role in regulating the balance between cell death and cell survival, and is implicated in tumorigenesis. Bcl-2, an anti-apoptotic protein, is a central player in various human cancers, promoting cell survival, angiogenesis, and chemotherapy resistance. This article reviews the history and development of Bcl-2-targeting antisense oligonucleotides (ASO), their optimization, clinical trials, and promising candidates.
Article
Cell Biology
Fan Luo, Fei-Teng Lu, Miao-Zhen Qiu, Ting Zhou, Wen-Juan Ma, Min Luo, Kang-Mei Zeng, Qiu-Yun Luo, Wen-Tao Pan, Lin Zhang, Zeng-Fei Xia, Zhong-Han Zhang, Jia-Xin Cao, Hong-Yun Zhao, Li Zhang, Da-Jun Yang
Summary: The combination of APG-1252 and gemcitabine exhibits synergistic anticancer activities against nasopharyngeal carcinoma (NPC), providing a promising treatment modality for patients. This combination enhanced NPC cell apoptosis and inhibited invasion, migration, and proliferation both in vitro and in vivo through various mechanisms including caspase-dependent pathways and blocking signaling pathways. Results suggest a potential new therapeutic strategy for advanced NPC.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Jason J. Zoeller, Michael F. Press, Laura M. Selfors, Judy Dering, Dennis J. Slamon, Sara A. Hurvitz, Joan S. Brugge
Summary: The study found upregulation of BCL2 mRNA in patients treated with lapatinib, but in some HER2+/ER- tumors, BCL-2 protein levels were undetectable. Unlike lapatinib, similar BCL-2 upregulation was not observed in patients treated with trastuzumab.
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
Malgorzata Opydo, Anna Mlyczynska, Ewa Mlyczynska, Agnieszka Rak, Elzbieta Kolaczkowska
Summary: Acute myeloid leukemia (AML) is a blood cancer characterized by abnormal cell proliferation and inhibition of apoptosis. The MCL-1 protein plays a critical role in the survival of AML cells. This study investigated the effects of a specific MCL-1 inhibitor, S63845, alone and in combination with other inhibitors, on AML cell lines. The results showed that S63845 decreased cell viability and induced apoptosis, and combined treatment enhanced apoptosis and induced cell differentiation. These findings suggest the potential use of MCL-1 inhibitors in combination with other pro-survival protein inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Pin-Han Chen, Tsai-Ching Hsueh, Jen-Leih Wu, Jiann-Ruey Hong
Summary: This study demonstrates that infectious spleen and kidney necrosis virus (ISKNV) infection can induce host cell death through the regulation of mitochondrial membrane potential. The dynamic interaction between pro-apoptotic and anti-apoptotic members of the Bcl-2 family plays a crucial role in this process.
Article
Neurosciences
Wei-Zhong Zhao, Hsiang-Tsui Wang, Hui-Ju Huang, Yu-Li Lo, Anya Maan-Yuh Lin
MOLECULAR NEUROBIOLOGY
(2018)
Article
Cell Biology
Ching-Ping Yang, Ming-Yuh Shiau, Yi-Ren Lai, Kuo-Ting Ho, Chiao-Wan Hsiao, Chun-Jung Chen, Yu-Li Lo, Yih-Hsin Chang
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2018)
Article
Biotechnology & Applied Microbiology
Shu-Ting Hong, Huaching Lin, Chen-Shen Wang, Chih-Hsien Chang, Anya Maan-Yuh Lin, James Chih-Hsin Yang, Yu-Li Lo
JOURNAL OF NANOBIOTECHNOLOGY
(2019)
Article
Chemistry, Multidisciplinary
Vivian Juang, Chih-Hsien Chang, Chen-Shen Wang, Hsin-Ell Wang, Yu-Li Lo
Article
Biochemistry & Molecular Biology
Shih-Yi Lin, Ching-Ping Yang, Ya-Yu Wang, Chiao-Wan Hsiao, Wen-Ying Chen, Su-Lan Liao, Yu-Li Lo, Yih-Hsin Chang, Chen-Jee Hong, Chun-Jung Chen
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Yu-Li Lo, Chen-Shen Wang, Yen-Chun Chen, Tse-Yuan Wang, Yih-Hsin Chang, Chun-Jung Chen, Ching-Ping Yang
Article
Medicine, General & Internal
Yi-Ying Lin, Yi-Ping Yang, Wei-Yi Lai, Chian-Shiu Chien, Shih-Jen Chen, De-Kuang Hwang, Ying-Hsiu Lai, Tai-Chi Lin, Shih-Hwa Chiou, Yu-Li Lo, Teh-Ia Huo, Yueh Chien
JOURNAL OF THE CHINESE MEDICAL ASSOCIATION
(2020)
Correction
Multidisciplinary Sciences
Yen-Ju Chen, Chia-Chi Hsu, Young-Ji Shiao, Hsiang-Tsui Wang, Yu-Li Lo, A. M. Y. Lin
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Hui-Ju Huang, Hsiang-Tsui Wang, Ting-Yu Yeh, Bo-Wei Lin, Young-Ji Shiao, Yu-Li Lo, Anya Maan-Yuh Lin
Summary: Selumetinib exhibits neuroprotective effects against acrolein-induced neurotoxicity by inhibiting the Nrf-2-HO-1 pathway, reducing protein conjugation and aggregation, attenuating damage in neurite outgrowth, and preventing cell death, suggesting its potential as a therapeutic agent for CNS neurodegenerative diseases.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Yu-Li Lo, Hua-Ching Lin, Shu-Ting Hong, Chih-Hsien Chang, Chen-Shen Wang, Anya Maan-Yuh Lin
Summary: TJ-modulating peptide-modified LPN is a potential platform for delivering chemotherapeutics across the BBB to the brain for the treatment of brain metastases from NSCLC. Afa/LPN-FD7 and Afa/LPN-CCD showed a sustained-release profile and enhanced cytotoxicity of Afa on PC9 cells, with effective activation of paracellular and transcellular pathways.
CANCER NANOTECHNOLOGY
(2021)
Article
Cell Biology
Yih-Hsin Chang, Hui-Ju Yang, Huan-Wen Chen, Chiao-Wan Hsiao, Yi-Chen Hsieh, Yu-Wei Chan, Shu-Wen Chang, Wei-Lun Hwang, Wei-Shone Chen, Hou-Hsuan Cheng, Teh-Ying Chou, Fu-Pang Chang, Hsiang-Ling Ho, Fang-Yeh Chu, Yu-Li Lo, Chun-Jung Chen, Hui-Fang Tsai, Ming-Yuh Shiau
Summary: This study uncovers molecular evidence to substantiate and elucidate the link between CRC and T2DM, as well as characterizing the roles of CRMP2 in CRC-DM. Altered metabolic adaptations are promising targets for anti-diabetic and cancer strategies.
Article
Pharmacology & Pharmacy
Yu-Li Lo, Tse-Yuan Wang, Chun-Jung Chen, Yih-Hsin Chang, Anya Maan-Yuh Lin
Summary: This study presents a one-shot formulation of miR-125 and Afa, which modulates critical proteins and inhibits metabolic reprogramming and tumor progression in gastric cancer cells by targeting EGFR and mTOR pathways.
Article
Biochemistry & Molecular Biology
Yih-Hsin Chang, Shu-Wen Chang, Wei-Ting Hsu, Ching-Ping Yang, Yu-Li Lo, Chun-Jung Chen, Hui-Fang Tsai, Ming-Yuh Shiau
Summary: This study investigates the regulation of CRMP2 in metabolic homeostasis and finds that hyperglycemia suppresses CRMP2 expression and adipogenesis. CRMP2 plays important roles in cell growth and differentiation, and its function needs to be finely controlled to meet cellular needs.
Article
Chemistry, Physical
Chen-Shen Wang, Chih-Hsien Chang, Tsai-Yu Tzeng, Anya Maan-Yuh Lin, Yu-Li Lo
Summary: Head and neck cancer (HNC) is characterized by high incidence and poor prognosis. Epirubicin, a potential chemotherapeutic, can be efficacious in HNC treatment. HuR knockout with CRISPR/Cas9 and the use of multifunctional nanoparticles for efficient drug delivery and gene-editing offer a promising therapeutic approach for HNC. The nanoparticles designed in this study showed specific tumor targeting, nuclear localization, and an enhanced therapeutic effect against HNC in preclinical models.
NANOSCALE HORIZONS
(2021)
Article
Medicine, Research & Experimental
Yu-Li Lo, Chih-Hsien Chang, Chen-Shen Wang, Muh-Hwa Yang, Anya Maan-Yuh Lin, Ci-Jheng Hong, Wei-Hsuan Tseng