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Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
HDACi are being actively pursued for the treatment of cancers. HDACi Vorinostat and Romidepsin are approved for treatment of cutaneous T cell lymphoma. HDACi has been shown to modulate tumor metabolism by virtue of its effect on gene expression. HDACi treatment was associated with a significant reduction in glucose uptake and glycolysis in breast, colon, lung and multiple myeloma cancer cell lines (Alcarraz-Vizan et al., 2010; Wardell et al., 2009; Amoedo et al., 2011; Rodrigues et al., 2015). Such alterations are driven by decreased expression glucose uptake transporters and key glycolytic enzymes (Wardell et al., 2009), and increase reliance on mitochondrial metabolism (Amoedo et al., 2011). These studies imply that HDACi might selectively target cancer cells with Warburg’s phenotype.
Emerging Biomedical Analysis
Published in Lawrence S. Chan, William C. Tang, Engineering-Medicine, 2019
As one can see, one of the key elements allowing for the development of this diagnostic method was the discovery of a tumor-specific metabolite. A recent finding revealed that there was a mutation of the isocitrate dehydrogenase-1 (IDH1) gene present in a large majority of the common brain tumor glioma, with elevated levels up to 100-fold compared to wild type IDH1. This mutation and resulting gain-of-function leads to the production of the tumor-specific metabolite, 2-hydroxyglutarate (2-HG), which is not present in normal tissue. Besides glioma, the IDH1 mutation is also found in acute myeloid leukemia, cholangiocarcinoma, chondrosarcoma, and T cell lymphoma. These findings gave a substantial advantage for the development of tumor margin detection using MS (Pope 2014). Alternatively, other chemicals, if substantially different in quantity between tumor and normal tissues, can also be used for this identification purpose.
Approaching Cancer Therapy with Ruthenium Complexes by Their Interaction with DNA
Published in Ajay Kumar Mishra, Lallan Mishra, Ruthenium Chemistry, 2018
Another novel ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide (CNEB) as (Ru(II)-CNEB) was found to interact with and inhibit M4-lactate dehydrogenase (M4-LDH), a tumor growth supportive enzyme, at the tissue level (Koiri et al., 2009). Modulation of M4-LDH by this compound in a T-cell lymphoma (Dalton’s Lymphoma: DL) causes regression of the tumor in vivo. The compound showed a dose-dependent cytotoxicity to DL cells in vitro. It has also been observed that Ru(II)-CNEB could decline expression of the inducible form of 6-phosphofructo-2-kinase (iPFK2: PFKFB3), a regulator of glycolysis in DL cells. The complex also activated superoxide dismutase activity but declined the levels of catalase and glutathione peroxidase to impose oxidative stress in the DL cells. This was found consistent with enhanced p53 (a tumor supressor protein) level, decline in Bcl2/Bax (Bax (an apoptosis promoter) and Bcl-2 (an apoptosis inhibitor)) ratio and activation of caspase 9 in those DL cells. The findings suggest that Ru(II)-CNEB is able to activate oxidative stressapoptosis pathway via p53-mediated repression of iPFK2, a key glycolytic regulator, in the DL cells in vivo. These findings provide a biochemical mechanism which can be utilized for defining pharmacological targets for the novel anticancer agents suitable for in vivo applications (Koiri et al., 2015).
Anticancer activity of vanadium nanoparticles against human breast cancer: an in vitro study
Published in Inorganic and Nano-Metal Chemistry, 2023
Canan Vejselova Sezer, Hatice Mehtap Kutlu
The anticancer effect of vanadium has been investigated in many malignant cell lines, with their biochemical and molecular mechanisms. These cell lines are B- and T-cell lymphoma, hepatoma, osteosarcoma, testicular, breast, uterine, kidney, lung, nasopharynx, and esophageal carcinoma cells.[11,12] Researchers have shown the antitumor effect of (+4) sodium metavanadate and (+4) vanadyl sulfate as vanadium compounds in many in vitro studies on lymphoma, T-cell leukemia, erythroleukemia, basophilic leukemia, liver cancer, ovarian cancer, testicular cancer, and cancers of esophagus and bone.[6,13,14] It has also been demonstrated that vanadium (NaVO3) inhibits cancer cell viability in human lung (A549) and breast cancer (A549) cells.[5] The cytotoxic and antitumor effects of vanadyl sulfate and bis malato orthovanadium on mouse fibrosarcoma cells (L929), rat pheochromocytoma cells (PC12), human liver carcinoma cells (HepG2) and mouse embryonic fibroblast cells (NIH/3T3) were investigated in various studies. It was found that its cytotoxic effect on 3T3 cells was lower than its cytotoxic effect on other tested cancer cells, and that this cytotoxicity varied depending on the dose and cell type.[15]
The biological and therapeutic potentials of Cyclotrichium genus: a systematic review
Published in International Journal of Environmental Health Research, 2022
Homayoon Yazdanshenas, Majid Tafrihi
The cytotoxic effect of the above-mentioned compounds can effectively inhibit tumor growth but they may not be the promising cure for cancer, since multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Crippling the MDR mechanisms of cancer cells by inducing MDR reversal effects on cancer cells might increase the effect of cytotoxic drugs on cancer cells (Nooter and Herweijer 1991; Nooter and Stoter 1996). Most Cyclotrichium plants contain a noticeable amount of spathulenol (Figure 2), tricyclic sesquiterpene alcohol (Toyota et al. 1996). The ABCB1 pump (commonly known as P-gp) is overexpressed in human multidrug-resistant cancer cells (Hodges et al. 2011). Martins et al. showed that the treatment of L5178 mouse T-cell lymphoma with pHa MDR1/A retrovirus (which overexpresses the ABCB1 efflux pump), and spathulenol resulted in the accumulation of rhodamine123 (substrate of the ABCB1) inside the cells. They concluded that spathulenol may be a promising compound in the reversal of multidrug resistance in MDR-expressing cancer cells (Martins et al. 2012).
A comprehensive summary of disease variants implicated in metal allergy
Published in Journal of Toxicology and Environmental Health, Part B, 2022
In addition to the many variants of ASIA that were correlated with metal hypersensitivity, allergic reactivity to sensitizing metals was also suggested to play a role in the promotion of a certain type of cancer – cutaneous T-cell lymphoma (CTCL). Many subtypes of CTCL were identified, but all variants of the disease are classified as extranodal non-Hodgkin’s lymphomas, wherein malignant monoclonal T-lymphocytes selectively infiltrate the skin (Bagherani and Smoller 2016). In the early stages of disease development, CTCL is often misdiagnosed as one of many common inflammatory skin conditions including ACD, psoriasis, lichen planus, folliculitis, or vitiligo (Hristov, Tejasvi, and R 2021). Interestingly, many subjects that develop CTCL have a history of these and other similar skin disorders. It is believed that these conditions often represent a precursor to cancerous transformation due to recurrent antigenic stimulation associated with chronic disease states. Accordingly, several cases of CTCL were correlated with chronic ACD induced by Cr, Ni, and Co (Khamaysi et al. 2011; Tilakaratne and Sidhu 2015).