Review
Immunology
Bengisu Molyer, Ashok Kumar, Jonathan B. Angel
Summary: SMAC mimetics are being explored as a potential approach to eliminate HIV-infected cells, with the ability to reverse HIV latency and/or kill persistently infected cells. Their research and development could play a crucial role in future HIV cure strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maria Vougioukalaki, Konstantina Georgila, Emmanouil Athanasiadis, Aristides G. Eliopoulos
Summary: This study reveals that detached carcinoma cells and immortalized fibroblasts exhibit defects in signaling pathways induced by TNF and CD40L, leading to increased sensitivity to death-inducing receptor ligands. The findings suggest a new mode of regulation of TNF family signal transduction by adhesion-related molecules, which may have significant implications for cancer therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Inhwan Bae, Daejin Kim, Jaeyul Choi, Jisook Kim, Minjeong Kim, Bokyung Park, Young Hoon Kim, Young Gil Ahn, Ha Hyung Kim, Dae Kyong Kim
Summary: The newly designed and synthesized bivalent analogue 27 showed significant increase in cellular activity and caused substantial tumor regressions in MDA-MB-231 xenograft model, indicating its promising potential as an effective anti-tumor agent.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Oncology
Annkathrin Koch, Birte Jeiler, Jens Roedig, Sjoerd J. L. van Wijk, Nadezda Dolgikh, Simone Fulda
Summary: Burkitt's lymphoma (BL) is a highly aggressive form of B-cell non-Hodgkin's lymphoma. While clinical outcomes in children have improved in recent years, the prognosis for adults remains poor. Research has shown that combination treatment with Smac mimetic BV6 and TRAIL can induce necroptosis in BL, highlighting the potential for novel treatment strategies. These findings demonstrate the critical role of MLKL in necroptotic signaling and suggest that MLKL may serve as a prognostic marker for the success of necroptosis-based therapies in BL.
Article
Nutrition & Dietetics
Thanpisit Lomphithak, Patthorn Jaikla, Apiwit Sae-Fung, Sasiprapa Sonkaew, Siriporn Jitkaew
Summary: Cholangiocarcinoma (CCA) is a highly aggressive cancer with poor prognosis and low survival rates. Flavonoids, such as quercetin and kaempferol, have shown potential in cancer therapy by targeting multiple genes. In this study, network pharmacology and bioinformatic analysis identified G2/M-related genes as potential targets of quercetin and kaempferol. In vitro experiments demonstrated that these flavonoids induced cell-cycle arrest in the G2/M phase and synergistically induced necroptosis in CCA cells when combined with a Smac mimetic LCL-161.
Article
Biology
Sahar Rafat, Prabhakar Singh, Kamlesh Kumar Pandey, Saleh A. Almatroodi, Mohammed A. Alsahli, Ahmad Almatroudi, Arshad Husain Rahmani, Kapil Dev
Summary: This study investigates the role of SMAC mimetic compound BV6 in regulating cell death mechanisms and its potential anti-cancer effect in combination with TRAIL and TNFα in breast cancer cells. The study suggests that BV6 alone and in combination with TRAIL and TNFα show promising results in inhibiting cancer growth. Additionally, IAPs and autophagic proteins may serve as important targets for the development of novel anti-cancer drugs.
Article
Biochemistry & Molecular Biology
Sahar Rafat, Mohammed Ageeli Hakami, Ali Hazazi, Ahad Amer Alsaiari, Summya Rashid, Mohammad Raghibul Hasan, Abdulaziz A. Aloliqi, Alaa Abdulaziz Eisa, Mohammad Irfan Dar, Mohd Faisal Khan, Kapil Dev
Summary: Breast cancer is the leading cause of death in women, with over a million deaths each year. The failure in regulating the cell death mechanism and the role of ROS contribute to the ineffectiveness and insufficiency of current therapeutic options against hormonally responsive breast cancers. This study investigates the therapeutic benefits of Smac mimetic compound BV6 on MCF7 breast cancer cells, showing its potential in reducing viability, inducing apoptosis, suppressing autophagy, and protecting against oxidative stress caused by H2O2. Smac mimetic compounds like BV6 may be used as anti-cancer drugs and antioxidants alone or in combination with commonly used antioxidants.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Lidia F. Hernandez, Angie B. Dull, Soumya Korrapati, Christina M. Annunziata
Summary: Ovarian cancer, the most lethal gynecological cancer in the US, is characterized by resistance to chemotherapy. Low Caspase 8 expression levels are associated with resistance to apoptotic chemotherapy in ovarian cancers. Combination treatment with a Smac-mimetic can increase cell death in tumor cells with low Caspase 8, leading to decreased tumor growth and enhanced overall survival in mouse models. Timing of drug administration is crucial for optimizing treatment outcomes.
CELL DEATH DISCOVERY
(2021)
Article
Oncology
Stephanie Chow, Oliver Dorigo
Summary: Adoptive cell transfer of IFN-activated monocytes administered intraperitoneally showed antitumor effects and acceptable tolerability in patients with platinum-resistant ovarian cancer. Exposure of monocytes to IFN-α and IFN-γ upregulated TRAIL, leading to caspase 8 activation and direct cell-to-cell contact-dependent apoptosis of ovarian cancer cells.
CLINICAL CANCER RESEARCH
(2023)
Review
Cell Biology
Grant R. Campbell, Stephen A. Spector
Summary: Effective antiretroviral therapy has significantly suppressed HIV-1 and improved immune function, but the persistence of integrated proviral DNA in latently infected cells remains a major obstacle to a cure. The kick and kill approach, aiming to activate HIV-1 expression to expose latently infected cells for immune clearance, faces challenges due to the complexity of the latent reservoir. Emphasis is now shifting towards a functional cure, focusing on permanently silencing HIV-1 transcription to achieve long-term drug-free remission. Exploiting autophagy to selectively kill HIV-1 latently infected cells is proposed as a promising strategy to decrease the size of the reservoir and potentially eradicate HIV-1 completely.
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
Hematology
Liang Zhou, Yu Zhang, Mark B. Meads, Yun Dai, Yanxia Ning, Xiaoyan Hu, Lin Li, Kanika Sharma, Jewel Nkwocha, Rebecca Parker, Danny Bui, Jacquelyn McCarter, Lora Kramer, Cullen Purcell, Praneeth R. Sudalagunta, Rafael R. Canevarolo, Maria D. Coelho Siqueira Silva, Gabriel De Avila, Raghunandan Reddy Alugubelli, Ariosto S. Silva, Maciej Kmeiciak, Andrea Ferreira-Gonzalez, Kenneth H. Shain, Steven Grant
Summary: The combination of LCL161 and LBH589 showed synergistic interactions in inducing apoptosis in human multiple myeloma cells by inactivating the noncanonical NF-kappa B pathway and activating the extrinsic apoptotic pathway. This treatment strategy was effective in primary MM cells and overcame various forms of resistance, demonstrating significant anti-tumor activity in vivo, suggesting its potential as a novel therapeutic approach in MM.
Article
Medicine, Research & Experimental
Grant R. Campbell, Jia Zhuang, Gang Zhang, Igor Landa, Luke J. Kubiatowicz, Diana Dehaini, Ronnie H. Fang, Liangfang Zhang, Stephen A. Spector
Summary: This study demonstrates that DIABLO/SMAC mimetic loaded TNP have outstanding neutralizing breadth and potency against HIV-1, selectively killing HIV-1-infected cells through autophagy-dependent apoptosis with no off-target or cytotoxic effects on bystander cells. Genetic inhibition of early stages of autophagy abolishes this effect, indicating the potential of TNP as therapeutic agents for HIV-1 treatment.
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)
Review
Biochemistry & Molecular Biology
Raffaele Frazzi
Summary: BIRC3 and BIRC5 are members of the IAPs family, with the former potentially promoting survival in cancer cells while the latter is often considered an anti-apoptotic molecule. Their roles in different types of tumors vary and their potential as therapeutic targets is still under investigation.
CELL AND BIOSCIENCE
(2021)
Article
Oncology
Milena Perrone, Claudia Chiodoni, Mara Lecchi, Laura Botti, Barbara Bassani, Annamaria Piva, Elena Jachetti, Matteo Milani, Daniele Lecis, Elda Tagliabue, Paolo Verderio, Sabina Sangaletti, Mario P. Colombo
Summary: Cancer can reprogram the bone marrow niche through the BM mesenchymal stem cells (MSC) and IL-1B/ATF3 signaling pathway, which promotes myeloid cell differentiation and tumor development. The expression of CD11b thorn population in the peripheral blood can be used as a potential biomarker for early diagnosis of breast cancer. This study suggests that targeting IL-1B or ATF3 may have therapeutic benefits for breast cancer patients.
Article
Biochemistry & Molecular Biology
Gemma Gorla, Tatiana Carrozzini, Giuliana Pollaci, Antonella Potenza, Sara Nava, Francesco Acerbi, Paolo Ferroli, Silvia Esposito, Veronica Saletti, Emilio Ciusani, Aida Zulueta, Eugenio A. Parati, Anna Bersano, Laura Gatti, Ignazio G. Vetrano
Summary: This study aimed to assess the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins in the plasma and CSF of pediatric MMA patients to clarify the pathogenesis and progression of the disease. The study found increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF. These findings provide valuable insights into the disease's mechanism and progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marika A. Franczak, Oliwia Krol, Gabriela Harasim, Agata Jedrzejewska, Nadia Zaffaroni, Carlotta Granchi, Filippo Minutolo, Amir Avan, Elisa Giovannetti, Ryszard T. Smolenski, Godefridus J. Peters
Summary: Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. In this study, the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration was investigated. The inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were most effective in cells with the highest metabolic modulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Silvia Gobbi, Silvia Martini, Riccardo Rozza, Angelo Spinello, Jessica Caciolla, Angela Rampa, Federica Belluti, Nadia Zaffaroni, Alessandra Magistrato, Alessandra Bisi
Summary: In this study, novel compounds with dual AR and ER activity were designed by modifying flavonoid-related compounds. Compounds 3b and 4a showed promising submicromolar activity against both targets. Computational studies confirmed the feasibility of using multi-target approaches for ER+ BC treatment. The homoisoflavone core emerged as a valuable scaffold for the design of multifunctional compounds.
Article
Oncology
Chiara Vasco, Ambra Rizzo, Chiara Cordiglieri, Elena Corsini, Emanuela Maderna, Emilio Ciusani, Andrea Salmaggi
Summary: Metastasis refers to the spread of a tumor from its original site to other parts of the body. This study focused on brain metastasis and used an in vitro model to investigate the ability of breast and lung tumor cells to cross the blood-brain barrier, as well as the expression of adhesion molecules. The study also found that vesicles released by tumor cells can induce cell death in endothelial cells.
Article
Pharmacology & Pharmacy
Martina Pedrini, Angelo Iannielli, Lorenzo Meneghelli, Daniele Passarella, Vania Broccoli, Pierfausto Seneci
Summary: The rational design of a small array of six Anle138b-centered PROTACs, 7a,b, 8a,b and 9a,b, targeting aSynuclein (aSyn) aggregates for binding, polyubiquitination by the E3 ligase Cereblon (CRBN), and proteasomal degradation, was used in the search for disease-modifying agents targeted against Parkinson's disease. Lenalidomide and thalidomide served as CRBN ligands and were coupled with amino- and azido Anle138b derivatives through flexible linkers and coupling reactions. Four Anle138b-PROTACs, 8a,b and 9a,b, were tested against aSyn aggregation in vitro using Thioflavin T (ThT) fluorescence assay and dopaminergic neurons derived from SNCA multiplications. The most promising inhibitor/degradation inducer of aSyn aggregation was identified as Anle138b-PROTAC 8a, which may have potential applications in synucleinopathies and cancer.
Article
Chemistry, Medicinal
Antonia I. Antoniou, Giulia Nordio, Maria Luisa Di Paolo, Eleonora Colombo, Beatrice Gaffuri, Laura Polito, Arianna Amenta, Pierfausto Seneci, Lisa Dalla Via, Dario Perdicchia, Daniele Passarella
Summary: 2-Hydroxyoleic acid (6, 2OHOA), a nontoxic antitumor drug, was used to form nanoparticles (NPs) in water and enhance cell penetration and drug release. The synthesized NP formulations showed antiproliferative activity against human tumor cell lines. The disulfide-containing linker in the nanoformulations promoted cellular effects.
Editorial Material
Biochemistry & Molecular Biology
Anna Bersano, Laura Gatti
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Antonella Potenza, Gemma Gorla, Tatiana Carrozzini, Anna Bersano, Laura Gatti, Giuliana Pollaci
Summary: Stroke is a leading cause of death and disability globally. It is important to find new circulating biomarkers that can distinguish and monitor cerebrovascular diseases leading to stroke. Biomarkers can provide additional information to improve diagnosis, prognosis, and identify potential therapeutic targets for personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tatiana Carrozzini, Giuliana Pollaci, Gemma Gorla, Antonella Potenza, Nicola Rifino, Francesco Acerbi, Ignazio G. G. Vetrano, Paolo Ferroli, Anna Bersano, Erica Gianazza, Cristina Banfi, Laura Gatti
Summary: Moyamoya angiopathy (MMA) is a rare cerebrovascular disease characterized by progressive steno-occlusive lesions and collateral vessel development. Surgical treatment, particularly indirect revascularization, is preferred. By performing proteomic characterization, a potential gene, Filamin A, was identified, suggesting a role in MMA pathogenesis. This study provides insights into the molecular understanding of this disabling intracranial vasculopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Eleonora Colombo, Stefania Olla, Cristina Minnelli, Alessia Formato, Caterina Veroni, Silvia Corbisiero, Mattia Pericolo, Chiara Siguri, Giovanna Mobbili, Cristina Agresti, Pierfausto Seneci
Summary: In this study, twelve analogues of Edaravone (EDA) were synthesized to find potential remyelinating agents for multiple sclerosis treatment and identify their molecular targets. The compounds were evaluated using three primary assays, and a suitable EDA 1 prodrug for in vivo testing was selected.
Article
Chemistry, Medicinal
Roberta Mancuso, Lorenzo Agostino Citterio, Simone Agostini, Ivana Marventano, Francesca La Rosa, Francesca Re, Pierfausto Seneci, Marina Saresella, Mario Clerici, Leonidas A. Phylactou
Summary: The anti-hyperglycemic drug glibenclamide and bi-functionalized liposomes are capable of inhibiting NLRP3 inflammasome activation and reducing the release of inflammatory cytokines. They also have the ability to modulate the expression of certain miRNAs. These findings suggest a potential new strategy for treating neurodegenerative diseases using glibenclamide and liposomes.
Article
Chemistry, Analytical
Silvia Picciolini, Francesca Roda, Alice Gualerzi, Valentina Mangolini, Luana Forleo, Aurora Mangolini, Silvia Sesana, Antonia Antoniou, Francesca Re, Pierfausto Seneci, Marzia Bedoni
Summary: This study presents the use of Surface Plasmon Resonance imaging (SPRi) for characterization of multifunctionalized liposomes designed for targeted Glioblastoma treatment, showing promising results in targeting brain and diseased areas.
Meeting Abstract
Biochemistry & Molecular Biology
Gemma Gorla, Giuliana Pollaci, Antonella Potenza, Tatiana Carrozzini, Isabella Canavero, Nicola Rifino, Benedetta Storti, Anna Bersano, Laura Gatti
JOURNAL OF NEUROCHEMISTRY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Giuliana Pollaci, Antonella Potenza, Aida Zulueta, Gemma Gorla, Tatiana Carrozzini, Isabella Canavero, Benedetta Storti, Nicola Rifino, Marcella Catania, Giuseppe Di Fede, Anna Bersano, Laura Gatti
JOURNAL OF NEUROCHEMISTRY
(2023)