scholarly journals Effect of Monoclonal Antibodies Conjugation With Gallium-Containing Solamargine: Warburg Effect- Based Cancer Therapeutic Strategy. Article Review

2021 ◽  
pp. 47-59
Author(s):  
Waleed O. Atta
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Therapeutic Strategy ◽  
Aerobic Glycolysis ◽  
Malignant Cells ◽  
Long Time ◽  
High Degree

Therapy by Monoclonal antibodies is considered extremely hoping method for cancer therapy. But cancer cells have variable methods for resistance by multiple genetic mutations. The aim of that article to illustrate tagging monoclonal antibodies by gallium containing solamargine glycoside within the antibody by glycosylation the asparagine of its Fc portion. Malignant cells need to a big extent high carbohydrate content for aerobic glycolysis for cancer progression. Solamargine as a specific glycoside can be diffused easily and effectively into malignant cells with a high degree of specificity. Complexion gallium to solamargine then conjugation into monoclonal antibodies will increase Monoclonal antibody potency and affinity by Warburg effect based mechanism and gallium particles. Gallium can be retained for a long time inside malignant cells. By that method, the monoclonal antibody will be targeted to cancer cells by solamargine, retained gallium particles besides its functioning specific Fab region.

Pieces of the complex puzzle of cancer cell energy metabolism: an overview of energy metabolism and alternatives for targeted cancer therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Zeinab Ghasemishahrestani ◽  
Larissa Maura Melo Mattos ◽  
Tatiana Martins Tilli ◽  
André Souza dos Santos ◽  
Marcos Dias Pereira
Keyword(s):  
Energy Metabolism ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Warburg Effect ◽  
Cell Biology ◽  
Aerobic Glycolysis ◽  
Target Therapy ◽  
Cell Metabolism ◽  
Cancer Cell Metabolism

Over the past decades, several advances in cancer cell biology have led to relevant details about a phenomenon called "Warburg effect". Currently, it has been accepted that Warburg effect is not anymore compatible with all cancer cells, and thus the process of aerobic glycolysis is now challenged by the knowledge of a large number of cells presenting mitochondrial function. The energy metabolism of cancer cells is focused in the bioenergetic and biosynthetic pathways to meet the requirements of rapid proliferation. Changes in the metabolism of carbohydrate, amino acids and lipids have already been reported in cancer cells and might play relevant roles for cancer progression. To the best of our knowledge, mostly of these changes are established, mainly due to genetic reprogramming that leads to the transformation of a healthy into a cancerous cell. Indeed, several enzymes of high relevance for the energy are targets of oncogenes (ex. PI3K, HIF1 and Myc) and tumor suppressor proteins (ex. p53). As a consequence of the extensive study on cancer cell metabolism, some new therapeutic strategies have appeared that aim to interrupt the aberrant metabolism, as well as the influence of genetic reprogramming in cancer cells. In this perspective, we briefly review the cancer cell metabolism (carbohydrate, amino acid and lipid), and also describe oncogenes and tumor suppressors that affect cancer cell metabolism. We also discuss some potential candidates for target therapy to disrupt the main driven-force for cancer cell metabolism and proliferation.

Therapeutic Monoclonal Antibodies in Clinical Practice against Cancer

2020 ◽  
Vol 20 (16) ◽  
pp. 1895-1907
Author(s):  
Navgeet Kaur ◽  
Anju Goyal ◽  
Rakesh K. Sindhu
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Therapeutic Agent ◽  
Hematologic Malignancies ◽  
Immune Checkpoints ◽  
Malignant Cells ◽  
Main Target ◽  
Therapeutic Monoclonal Antibodies ◽  
Cancerous Cells

The importance of monoclonal antibodies in oncology has increased drastically following the discovery of Milstein and Kohler. Since the first approval of the monoclonal antibody, i.e. Rituximab in 1997 by the FDA, there was a decline in further applications but this number has significantly increased over the last three decades for various therapeutic applications due to the lesser side effects in comparison to the traditional chemotherapy methods. Presently, numerous monoclonal antibodies have been approved and many are in queue for approval as a strong therapeutic agent for treating hematologic malignancies and solid tumors. The main target checkpoints for the monoclonal antibodies against cancer cells include EGFR, VEGF, CD and tyrosine kinase which are overexpressed in malignant cells. Other immune checkpoints like CTLA-4, PD-1 and PD-1 receptors targeted by the recently developed antibodies increase the capability of the immune system in destroying the cancerous cells. Here, in this review, the mechanism of action, uses and target points of the approved mAbs against cancer have been summarized.

Mitophagy in Carcinogenesis and Tumor progression- A New paradigm with Emerging Importance

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman K. Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Mammalian Cells ◽  
Mitochondrial Dynamics ◽  
Clinical Importance ◽  
Malignant Cells ◽  
Malignant Growth ◽  
New Paradigm ◽  
Pancreatic Cancer Cells

: The term Mitophagy has been newly concerned in reforming metabolic landscape inside cancerous cells in addition to interface between malignant cells as well as other major constituents of tumor microenvironment. Several profoundly interrelated systems, comprising mitochondrial dynamics and mitophagy, function in mammalian cells as vital mitochondrial regulator process, and their consequence in neoplastic development has newly illuminated clinically. In specific instance of cancer cells, mitochondrialprotected metabolic paths are revamped to meet expanded bioenergetics along with biosynthetic necessities of malignant cells in addition to deal with oxidative stress. It is an exhausting task to foresee the role that mitophagy has on malignant growth cells since it relies upon various elements like cancer variability, malignant growth phase, genetic background and harmony between cell demand and accessibility. As per condition, mitophagy may have a double role as cancer suppressor for example Atg5 (autophagy related 5) or Atg7 (autophagy related 7) or execute promoter like function for instance FUNDC1 (FUN14 domain-containing protein 1), BNIP3 (BCL2/adenovirus E1B 19-kDa-interacting protein 3), PINK1 (PTEN-instigated kinase 1) etc. Tumor suppressive function of Parkin (E3 ubiquitin ligase) is likewise distinguished in mammary gland carcinoma where obstruction of mitophagy impacts tumor progression. In pancreatic cancer cells and in hepatocellular carcinoma hypermethylation of the BNIP3, promoter occurs that prevent HIF-1 (HypoxiaInducible Factor 1) binding besides ensuing initiation of mitophagy. Since the double role mitophagy has in malignant growth relying upon various circumstances and cell varieties, a range of studies have been going on mitophagy and its role in cancer progression and development is opening up a new paradigm with immense clinical importance.

scholarly journals Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

2020 ◽  
Vol 21 (5) ◽  
pp. 1661
Author(s):  
Anamarija Mojzeš ◽  
Marko Tomljanović ◽  
Lidija Milković ◽  
Renata Novak Kujundžić ◽  
Ana Čipak Gašparović ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Warburg Effect ◽  
Aerobic Glycolysis ◽  
Intracellular Localization ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Warburg Effect

In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription 3 (STAT3) proteins were analyzed by Western blot. The response to ethanol and curcumin seemed to be cell-type specific, with respect to all parameters analyzed. High sensitivity to curcumin was present in the cell lines originating from head and neck squamous cell carcinomas: FaDu, Detroit 562 and, especially, Cal27. Very low sensitivity was observed in the colon adenocarcinoma-originating HT-29 cell line, which retained, after exposure to curcumin, a higher levels of lactate production despite decreased glucose consumption. The effects of ethanol were significant.

scholarly journals Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 270 ◽  
Author(s):  
Gabriela Reyes-Castellanos ◽  
Rawand Masoud ◽  
Alice Carrier
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Mitochondrial Metabolism ◽  
Metabolic Reprogramming ◽  
Ductal Adenocarcinoma ◽  
Current View ◽  
Pancreatic Cancer Cells

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago (“Warburg effect” or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. There is now accumulating evidence that most cancers also rely on mitochondria to satisfy their metabolic needs. Indeed, the current view of cancer metabolism places mitochondria as key actors in all facets of cancer progression. Importantly, mitochondrial metabolism has become a very promising target in cancer therapy, including for refractory cancers such as Pancreatic Ductal AdenoCarcinoma (PDAC). In particular, mitochondrial oxidative phosphorylation (OXPHOS) is an important target in cancer therapy. Other therapeutic strategies include the targeting of glutamine and fatty acids metabolism, as well as the inhibition of the TriCarboxylic Acid (TCA) cycle intermediates. A better knowledge of how pancreatic cancer cells regulate mitochondrial metabolism will allow the identification of metabolic vulnerabilities and thus novel and more efficient therapeutic options for the benefit of each patient.

scholarly journals Anti-Warburg effect by targeting HRD1-PFKP pathway may inhibit breast cancer progression

2020 ◽  
Author(s):  
Ya Fan ◽  
Jia Wang ◽  
Yuemei Xu ◽  
Yipin Wang ◽  
Tao Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Cancer Cells ◽  
Warburg Effect ◽  
Breast Cancer Cells ◽  
Aerobic Glycolysis ◽  
Mass Spectrometry Analysis ◽  
Cancer Proliferation ◽  
Spectrometry Analysis ◽  
Proliferation And Invasion

Abstract Background: Our previous studies have shown that the E3 ubiquitin ligase of HMG-CoA reductase degradation 1 (HRD1) functions as a tumor suppressor, as overexpression of HRD1 suppressed breast cancer proliferation and invasion. However, its role in breast cancer cell glucose metabolism was unclear. Here, our aim was to uncover the role and molecular mechanisms of HRD1 in regulating aerobic glycolysis in breast cancer. Methods: The effect of HRD1 on robic glycolysis in breast cancer cells were assessed. Then the proliferation, colony formation ability, invasion and migration of breast cancer cells were evaluated. The relationship between HRD1 and PFKP was validated by Mass spectrometry analysis, immunofluorescence and co-immunoprecipitation. The level of PFKP ubiquitination was measured using ubiquitylation assay. Furthermore, the tumor growth and metastasis in mice xenografts were observed. Results: We found that upregulation of HRD1 clearly decreased aerobic glycolysis, and subsequently inhibited breast cancer proliferation and invasion. Mass spectrometry analysis results revealed a large HRD1 interactome, which included PFKP (platelet isoform of phosphofructokinase), a critical enzyme involved in the Warburg Effect in breast cancer. Mechanistically, HRD1 interacted and colocalized with PFKP in the cytoplasm, targeted PFKP for ubiquitination and degradation, and ultimately reduced PFKP expression and activity in breast cancer cells. HRD1 inhibited breast cancer growth and metastasis in vivo through a PFKP-dependent wayConclusions: Our findings reveal a new regulatory role of HRD1 in Warburg effect and provide a key contributor in breast cancer metabolism.

scholarly journals Panitumumab and cetuximab affect differently miRNA expression in colorectal cancer cells

2021 ◽  
Author(s):  
Romain Chautard ◽  
Laetitia Corset ◽  
Sajida Ibrahim ◽  
Céline Desvignes ◽  
Gilles Paintaud ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Two Phase ◽  
Colorectal Cancer Cells ◽  
Significant Expression ◽  
Antibody Resistance ◽  
Phase Process

Structured abstract Background & aim: Resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (CRC) is frequent and prognostic biomarkers are lacking. MicroRNAs (miR) are good candidates in this context. We aimed to characterize cetuximab and panitumumab exposure influence on miR expression in colorectal cancer cells to identify those regulating the EGFR pathway and implicated in resistance to treatment. Finally, we aimed to identify miR expression in serum of patients with advanced CRC treated with cetuximab or panitumumab. Results: Cetuximab and panitumumab exposure induced significant expression variations of 17 miR out of a miRnome panel of 752. Six of those miR interacted with at least one downstream element of the EGFR pathway. Conclusion: After the bioinformatics two-phase process, 5 miR rarely described before could be potential actors of anti-EGFR monoclonal antibody resistance: miR-95-3p, miR-139-5p, miR-145-5p, miR-429 and miR-1247-5p. In vivo, we detected the expression of miR-139-5p and miR-145-5p in serum of patients with metastatic CRC.

scholarly journals Dihydropyrimidinase Like 2 Promotes Bladder Cancer Progression via Pyruvate Kinase M2-Induced Aerobic Glycolysis and Epithelial–Mesenchymal Transition

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Zou ◽  
Ruiyan Huang ◽  
Yanfei Chen ◽  
Xiaoping Huang ◽  
Huajun Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Aerobic Glycolysis ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells ◽  
Malignant Behavior

BackgroundAerobic glycolysis and epidermal–mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression.MethodsThe expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression in vitro and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells.FindingsThe results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells in vitro, as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial–mesenchymal transition in bladder cancer cells.InterpretationIn conclusion, the results suggest that DPYSL2 promotes aerobic glycolysis and EMT in bladder cancer via PKM2, serving as a potential therapeutic target for bladder cancer treatment.

scholarly journals The Involvement of PPARs in the Peculiar Energetic Metabolism of Tumor Cells

2018 ◽  
Author(s):  
Andrea Antonosante ◽  
Michele d'Angelo ◽  
Vanessa Castelli ◽  
Mariano Catanesi ◽  
Dalila Iannotta ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
Cancer Metabolism ◽  
Cholesterol Metabolism ◽  
Aerobic Glycolysis ◽  
Acid Synthesis ◽  
Energetic Metabolism ◽  
Metabolic Alterations ◽  
Long Time

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

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