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
Biochemistry & Molecular Biology
Ravit Malishev, Shani Ben-Zichri, Ofek Oren, Nitzan Shauloff, Tal Peretz, Ran Taube, Niv Papo, Raz Jelinek
Summary: The BIM-BH3 motif is a key pro-apoptotic domain that forms toxic amyloid fibrils, leading to cell death and impacting mitochondrial functions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Akande Rouchidane Eyitayo, Mathilde Gonin, Hubert Arokium, Stephen Manon
Summary: BCL-2 family members are key regulators of apoptotic cell death in mammals. Studying their ectopic expression in yeast provides valuable insights into their function and regulation mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Chemistry, Medicinal
Samson Eugin Simon, Usman Ahmed, Syed Muhammad Saad, Ayaz Anwar, Khalid Mohammed Khan, Ee Wern Tan, Kuan Onn Tan
Summary: Chemo-resistant cancer cells can acquire robust growth potential through cell signaling mechanisms. Two bioactive compounds, SMS-IV-20 and SMS-IV-40, have been identified to exhibit elevated cytotoxicity against breast cancer cells and enhance chemo-sensitization. Both compounds interact with the MBR signaling pathway and exert antagonistic actions on BCL-2 and BCL-XL, resulting in the down-regulation of their expression and promotion of mitochondrial Cytochrome C release.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Yang Zhang, Maria A. Yapryntseva, Alexander Vdovin, Polina Maximchik, Boris Zhivotovsky, Vladimir Gogvadze
Summary: In a hypoxic environment, mimicking hypoxia with deferoxamine leads to resistance of tumor cells to anticancer drugs, reducing cell death and downregulating expression of apoptotic proteins.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Review
Oncology
Shanna Qian, Zhong Wei, Wanting Yang, Jinling Huang, Yinfeng Yang, Jinghui Wang
Summary: Apoptosis, a crucial biological process, plays a central role in cancer development and traditional cytotoxic therapies. The study of BCL-2 family proteins in regulating apoptosis and the development of anticancer drugs targeting BCL-2 anti-apoptotic proteins has gained increasing attention, showing great potential in cancer therapy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Deeksha Kaloni, Sarah T. Diepstraten, Andreas Strasser, Gemma L. Kelly
Summary: Acquired resistance to cell death is a key characteristic of cancer. The BCL-2 protein family members have important roles in regulating apoptotic cell death. Abnormal expression of pro-survival BCL-2 family proteins or reduction in pro-apoptotic BCL-2 family proteins, both leading to inhibition of apoptosis, are commonly observed in various types of cancer. The critical role of pro-survival and pro-apoptotic BCL-2 family proteins in apoptosis regulation makes them attractive targets for cancer treatment. This review discusses the roles of different pro-survival and pro-apoptotic members of the BCL-2 protein family in normal development and organismal function, as well as how defects in apoptosis control contribute to cancer development and therapy resistance. Lastly, the development of inhibitors targeting pro-survival BCL-2 proteins, known as BH3-mimetic drugs, as novel agents for cancer therapy is discussed.
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
Biochemistry & Molecular Biology
Jordan L. Morris, Germain Gillet, Julien Prudent, Nikolay Popgeorgiev
Summary: Bcl-2 family proteins are not only important regulators of apoptosis, but are also emerging as regulators of intracellular calcium concentrations. They interact with major calcium transporters at mitochondria-ER contact points, controlling mitochondrial calcium balance and impacting cell survival and migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Zhe Peng, Bernhard Gillissen, Antje Richter, Tobias Sinnberg, Max S. Schlaak, Juergen Eberle
Summary: Targeting MAP kinase pathways through BRAF inhibitors has shown promise in treating BRAF-mutated melanoma. However, this approach is ineffective for BRAF-WT melanoma, and relapse often occurs after initial regression. Inhibiting MAP kinase pathways downstream at ERK1/2 or targeting antiapoptotic Bcl-2 proteins like Mcl-1 may provide alternative strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Victoria Neely, Alekhya Manchikalapudi, Khanh Nguyen, Krista Dalton, Bin Hu, Jennifer E. Koblinski, Anthony C. Faber, Sumitra Deb, Hisashi Harada
Summary: By utilizing genomic and drug screening platform, we discovered a subset of small cell lung cancer (SCLC) cell lines that are highly sensitive to venetoclax, an FDA-approved BCL-2 inhibitor. These cell lines, SCLC-A (ASCL1 positive) and SCLC-P (POU2F3 positive), which represent 80% of SCLC cases, express high levels of BCL-2. However, some of these cell lines with high BCL-2 expression are resistant to venetoclax. Furthermore, most of these SCLC cell lines have TP53 missense mutations that result in gain-of-function activities, which may contribute to venetoclax resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Ryosuke Hiwa, Hailyn Nielsen, James L. Mueller, Ravi Mandla, Julie Zikherman
Summary: The NR4A family of orphan nuclear receptors plays redundant roles in establishing and maintaining Treg identity, and deletion of family members leads to Treg deficiency and severe inflammatory diseases. Through a competitive bone marrow chimera strategy, it was discovered that DKO bone marrow chimeras developed autoantibodies and inflammatory diseases despite having a Treg compartment mostly from WT origin. This study highlights the essential cell intrinsic roles of the NR4A family in central and peripheral T cell tolerance, demonstrating their importance in immune homeostasis.
Article
Biochemistry & Molecular Biology
Qiling Tang, Hongce Chen, Zihao Mai, Han Sun, LingJun Xu, Guihao Wu, Zhuang Tu, Xuecheng Cheng, Xiaoping Wang, Tongsheng Chen
Summary: Abivertinib (AC) is a novel epidermal growth factor receptor tyrosine kinase inhibitor that exhibits highly efficient antitumor activity. This study demonstrates that AC can induce both reactive oxygen species (ROS)-dependent apoptosis and ferroptosis in tumor cells. The Bim- and Bax-mediated mitochondrial pathways play a dominant role in AC-induced ferroptosis and apoptosis.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Cell Biology
Chendi Xie, Hui Zhou, Dongmei Qin, Huijian Zheng, Yuanfang Tang, Wenjuan Li, Jie Zhou, Long Liu, Xinxin Yu, Hongpeng Duan, Yong Zhou, Zhifeng Li, Zhihong Fang, Yiming Luo, Bing Z. Carter, Bing Xu, Jie Zha
Summary: This study found that the combination of Bcl-2 inhibitor venetoclax and PPARa agonist chiglitazar can effectively eliminate LSCs of acute myeloid leukemia (AML) without damaging normal cells. This combination therapy also significantly inhibits AML progression in mouse models.
CELL DEATH & DISEASE
(2023)
Letter
Gastroenterology & Hepatology
Sayed Aliul Hasan Abdi, Shatrunajay Shukla, Jasim Khan, Abdulaziz Al Zahrani
Summary: Acute myeloid leukaemia (AML) is a heterogeneous disease with limited traditional treatment options, leading to research on new therapies targeting AML leukemic stem cells through abnormal surface markers.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2021)
Article
Cell Biology
Jin Zhou, Brijesh K. Singh, Jia Pei Ho, Andrea Lim, Eveline Bruinstroop, Kenji Ohba, Rohit A. Sinha, Paul M. Yen
Summary: The study demonstrated that MED1 plays a crucial role in regulating hepatic autophagy, mitochondria function, and lipid metabolism. It may affect the transcriptional activity of various NRs and transcription factors, and contribute to the development of nonalcoholic fatty liver disease.
Article
Multidisciplinary Sciences
Winifred W. Yau, Kiraely Adam Wong, Jin Zhou, Nivetha Kanakaram Thimmukonda, Yajun Wu, Boon-Huat Bay, Brijesh Kumar Singh, Paul Michael Yen
Summary: The research found that autophagy plays a critical role in adaptive thermogenesis, fatty acid metabolism, and mitochondrial function in brown adipose tissue during chronic cold exposure. Studies on BAT from mice exposed to cold challenge and primary cells treated with norepinephrine showed that autophagy can increase BAT activity.
Article
Endocrinology & Metabolism
Dasan Mary Cibi, Reddemma Sandireddy, Hanumakumar Bogireddi, Nicole Tee, Siti Aishah Binte Abdul Ghani, Brijesh K. Singh, Nigel Mackman, Manvendra K. Singh, Anamika Singh
Summary: This study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HFpEF.
Article
Cell Biology
Anissa A. Widjaja, Jinrui Dong, Eleonora Adami, Sivakumar Viswanathan, Benjamin Ng, Leroy S. Pakkiri, Sonia P. Chothani, Brijesh K. Singh, Wei Wen Lim, Jin Zhou, Shamini G. Shekeran, Jessie Tan, Sze Yun Lim, Joyce Goh, Mao Wang, Robert Holgate, Arron Hearn, Leanne E. Felkin, Paul M. Yen, James W. Dear, Chester L. Drum, Sebastian Schafer, Stuart A. Cook
Summary: In the mouse model of APAP-induced liver injury, rhIL11 has been shown to be protective by inhibiting endogenous mouse IL11 activity. IL11 signaling is identified as a potential therapeutic target for APAP-induced liver damage, as its inhibition reduces liver injury and promotes survival in mice.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Madhulika Tripathi, Brijesh Kumar Singh, Elisa A. Liehn, Sheau Yng Lim, Keziah Tikno, David Castano-Mayan, Chutima Rattanasopa, Pakhwan Nilcham, Siti Aishah Binte Abdul Ghani, Zihao Wu, Syaza Hazwany Azhar, Jin Zhou, Sauri Hernandez-Resendiz, Gustavo E. Crespo-Avilan, Rohit Anthony Sinha, Benjamin Livingston Farah, Kyaw Thu Moe, Deidre Anne De Silva, Veronique Angeli, Manvendra K. Singh, Roshni R. Singaraja, Derek J. Hausenloy, Paul Michael Yen
Summary: Caffeine reduces vascular smooth muscle cell proliferation and restenosis by stimulating autophagy and inhibiting WNT signaling.
Article
Endocrinology & Metabolism
Eveline Bruinstroop, Jin Zhou, Madhulika Tripathi, Winifred W. Yau, Anita Boelen, Brijesh Kumar Singh, Paul M. Yen
Summary: The study found that in the early stages of nonalcoholic fatty liver disease, Dio1 gene expression and activity increased, which was associated with an increased T(3)/T-4 ratio. The results suggest that Dio1 regulates hepatic triglyceride content during hepatosteatosis and early nonalcoholic steatohepatitis.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Sangam Rajak, Pratima Gupta, Baby Anjum, Sana Raza, Archana Tewari, Sujoy Ghosh, Madhulika Tripathi, Brijesh K. Singh, Rohit A. Sinha
Summary: NASH is an important stage of NAFLD in humans, and there are currently no approved drugs for its treatment. The upregulation of AKR1B10 gene in NASH patients has been identified, and the inhibition of AKR1B10 has shown promising effects in reducing the pathological features of NASH.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Endocrinology & Metabolism
Jin Zhou, Madhulika Tripathi, Jia Pei Ho, Anissa Anindya Widjaja, Shamini Guna Shekeran, Macalinao Dominique Camat, Anne James, Yajun Wu, Jianhong Ching, Jean-Paul Kovalik, Kiat-Hon Lim, Stuart Alexander Cook, Boon-Huat Bay, Brijesh Kumar Singh, Paul Michael Yen
Summary: This study found that thyroid hormone can treat NASH-associated hepatic inflammation and fibrosis by promoting autophagy and mitochondrial biogenesis, increasing the oxidation of fatty acids, and reducing lipotoxicity, oxidative stress, and inflammation.
Editorial Material
Pharmacology & Pharmacy
Sugunadevi Sakkiah, Brijesh Kumar Singh, Keun Woo Lee, Chandrabose Selvaraj
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Gastroenterology & Hepatology
Madhulika Tripathi, Brijesh Kumar Singh, Jin Zhou, Keziah Tikno, Anissa Widjaja, Reddemma Sandireddy, Kabilesh Arul, Siti Aishah Binte Abdul Ghani, George Goh Boon Bee, Kiraely Adam Wong, Ho Jia Pei, Shamini Guna Shekeran, Rohit Anthony Sinha, Manvendra K. Singh, Stuart Alexander Cook, Ayako Suzuki, Teegan Reina Lim, Chang-Chuen Cheah, Jue Wang, Rui-Ping Xiao, Xiuqing Zhang, Pierce Kah Hoe Chow, Paul Michael Yen
Summary: The study reveals that hyperhomocysteinemia (HHcy) plays a key role in the pathogenesis of non-alcoholic steatohepatitis (NASH) through homocysteinylation of proteins, leading to autophagy blockage. Vitamin B-12 and folate may serve as a novel first-line therapy for NASH by reducing homocysteine levels and promoting autophagy, thus improving liver histology.
JOURNAL OF HEPATOLOGY
(2022)
Letter
Gastroenterology & Hepatology
Madhulika Tripathi, Brijesh Kumar Singh, Paul Michael Yen
JOURNAL OF HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Jin Zhou, Jeremy Pang, Madhulika Tripathi, Jia Pei Ho, Anissa Anindya Widjaja, Shamini Guna Shekeran, Stuart Alexander Cook, Ayako Suzuki, Anna Mae Diehl, Enrico Petretto, Brijesh Kumar Singh, Paul Michael Yen
Summary: The study found that spermidine can restore liver cell function impaired by non-alcoholic steatohepatitis (NASH) and prevent the progression of NASH in mice.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sangam Rajak, Archana Tewari, Sana Raza, Pratima Gupta, Bandana Chakravarti, Baby Anjum, Madhulika Tripathi, Brijesh K. Singh, Paul M. Yen, Amit Goel, Sujoy Ghosh, Rohit A. Sinha
Summary: Nonalcoholic steatohepatitis (NASH) is a pivotal stage in the progression of nonalcoholic fatty liver disease (NAFLD) and increases the risk of serious liver diseases. Identifying reliable molecular players in the etiology of NASH has been difficult. Furthermore, there are currently no approved drugs for NASH treatment. This study highlights the involvement of CFTR in the pathogenesis of NASH and suggests the possibility of its pharmacological inhibition in human NASH.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Madhulika Tripathi, Brijesh Kumar Singh
Summary: Orphan nuclear receptor estrogen-related receptor alpha (ERR alpha) plays a crucial role in regulating energy metabolism, but its hyperactivation in breast cancer leads to cell migration, proliferation, and tumour development. The study by Brindisi et al. reveals that cholesterol can activate ERR alpha endogenously, promoting breast cancer aggressiveness, highlighting the potential anti-tumour effects of cholesterol-lowering drugs like statins.