scholarly journals Extremely Low-Frequency Magnetic Fields and Redox-Responsive Pathways Linked to Cancer Drug Resistance: Insights from Co-Exposure-Based In Vitro Studies

2018 ◽  
Vol 6 ◽  
Author(s):  
Stefano Falone ◽  
Silvano Santini ◽  
Valeria Cordone ◽  
Giovanna Di Emidio ◽  
Carla Tatone ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Magnetic Fields ◽  
Low Frequency ◽  
In Vitro Studies ◽  
Cancer Drug ◽  
Extremely Low Frequency ◽  
Cancer Drug Resistance ◽  
Redox Responsive

scholarly journals Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance

2021 ◽  
Vol 14 (5) ◽  
pp. 470
Author(s):  
Nirmala Tilija Pun ◽  
Chul-Ho Jeong
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Drug Repurposing ◽  
Synergistic Action ◽  
Cancer Drug ◽  
Cancer Cell Proliferation ◽  
Cancer Drug Resistance ◽  
Anti Cancer

Cancer is incurable because progressive phenotypic and genotypic changes in cancer cells lead to resistance and recurrence. This indicates the need for the development of new drugs or alternative therapeutic strategies. The impediments associated with new drug discovery have necessitated drug repurposing (i.e., the use of old drugs for new therapeutic indications), which is an economical, safe, and efficacious approach as it is emerged from clinical drug development or may even be marketed with a well-established safety profile and optimal dosing. Statins are inhibitors of HMG-CoA reductase in cholesterol biosynthesis and are used in the treatment of hypercholesterolemia, atherosclerosis, and obesity. As cholesterol is linked to the initiation and progression of cancer, statins have been extensively used in cancer therapy with a concept of drug repurposing. Many studies including in vitro and in vivo have shown that statin has been used as monotherapy to inhibit cancer cell proliferation and induce apoptosis. Moreover, it has been used as a combination therapy to mediate synergistic action to overcome anti-cancer drug resistance as well. In this review, the recent explorations are done in vitro, in vivo, and clinical trials to address the action of statin either single or in combination with anti-cancer drugs to improve the chemotherapy of the cancers were discussed. Here, we discussed the emergence of statin as a lipid-lowering drug; its use to inhibit cancer cell proliferation and induction of apoptosis as a monotherapy; and its use in combination with anti-cancer drugs for its synergistic action to overcome anti-cancer drug resistance. Furthermore, we discuss the clinical trials of statins and the current possibilities and limitations of preclinical and clinical investigations.

Effects of co-exposure to extremely low frequency (50 Hz) magnetic fields and xenobiotics determined in vitro by the alkaline comet assay

2006 ◽  
Vol 361 (1-3) ◽  
pp. 208-219 ◽  
Author(s):  
Milena Villarini ◽  
Massimo Moretti ◽  
Giuseppina Scassellati-Sforzolini ◽  
Bruno Boccioli ◽  
Rossana Pasquini
Keyword(s):  
Magnetic Fields ◽  
Comet Assay ◽  
Low Frequency ◽  
Alkaline Comet Assay ◽  
Extremely Low Frequency

Effects of co-exposure to extremely low frequency (ELF) magnetic fields and benzene or benzene metabolites determined in vitro by the alkaline comet assay

2005 ◽  
Vol 157 (2) ◽  
pp. 119-128 ◽  
Author(s):  
Massimo Moretti ◽  
Milena Villarini ◽  
Stefano Simonucci ◽  
Cristina Fatigoni ◽  
Giuseppina Scassellati-Sforzolini ◽  
...  
Keyword(s):  
Magnetic Fields ◽  
Comet Assay ◽  
Low Frequency ◽  
Alkaline Comet Assay ◽  
Extremely Low Frequency

scholarly journals A Combination Strategy Targeting Enhancer Plasticity Exerts Synergistic Lethality Against Beti-Resistant Leukemia Cells

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5053-5053
Author(s):  
Lei Guo ◽  
Jia Li ◽  
Hongxiang Zeng ◽  
Anna Guzman ◽  
Tingting Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Rna Polymerase Ii ◽  
Conflicts Of Interest ◽  
Leukemia Cells ◽  
Cancer Drug ◽  
Distal Enhancer ◽  
Combination Strategy ◽  
Cancer Drug Resistance ◽  
Bet Inhibitors

Primary and acquired drug resistance is a major challenge to achieving optimized clinical outcomes during cancer treatment which can arise from transcription reactivation, bypass and alteration during anticancer treatment [1-3]. Epigenetic dysregulation is emerging as a crucial component involved in drug resistance. Transcriptional adaptation during drug treatment is often mediated by inducible histone modifications, especially histone H3 lysine 27 acetylation (H3K27ac) at the distal enhancer elements, thus activating the transcription of drug resistance-associated genes [4-6]. BRD4 (bromodomain-containing protein 4), a member of the bromodomain and extra-terminal domain (BET) family, acts as a chromatin reader to regulate transcription by linking histone acetylation and core components of the transcriptional apparatus [7]. BET inhibitors (BETi), as exemplified by JQ1 and I-BET151, have been shown to suppress the growth of multiple types of tumor both in vitro and in vivo [8]. However, drug resistance associated with BETi becomes one of the major hurdles hampering the clinical applications of these promising drug candidates [8, 9]. Using BET inhibitor (BETi) resistant leukemia cells as a model system, we demonstrated herein that genome-wide enhancer remodeling played a pivotal role in driving therapeutic resistance via compensational re-expression of pro-survival genes. Capitalizing on CRISPR interference, we identified the second intron of IncRNA, PVT1, as a unique bona fidegained enhancer that restored MYCtranscription independent of BRD4 recruitment. A combined BETi and CDK7 inhibitor treatment abolished MYC transcription by impeding RNAPII loading without affecting PVT1-mediated chromatin looping at the MYClocus in BETi-resistant leukemia cells. Furthermore, recipient mice transferred with BETi-resistant murine MLL-AF9 AML cells receiving the combination treatment showed the most effective therapeutic outcomes, as characterized by prolonged overall survival and reduced tumor burdens in the spleen and bone marrow. Together, our findings have established the feasibility of targeting enhancer plasticity to overcome drug resistance associated with epigenetic therapies. References 1. Mansoori, B., et al., The Different Mechanisms of Cancer Drug Resistance: A Brief Review.Adv Pharm Bull, 2017. 7(3): p. 339-348. 2. Konieczkowski, D.J., C.M. Johannessen, and L.A. Garraway, A Convergence-Based Framework for Cancer Drug Resistance.Cancer Cell, 2018. 33(5): p. 801-815. 3. Holohan, C., et al., Cancer drug resistance: an evolving paradigm.Nat Rev Cancer, 2013. 13(10): p. 714-26. 4. Zanconato, F., et al., Transcriptional addiction in cancer cells is mediated by YAP/TAZ through BRD4.Nat Med, 2018. 24(10): p. 1599-1610. 5. Takeda, D.Y., et al., A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer.Cell, 2018. 174(2): p. 422-432 e13. 6. Chen, X., et al., A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma.Nat Commun, 2018. 9(1): p. 2949. 7. Jang, M.K., et al., The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription.Mol Cell, 2005. 19(4): p. 523-34. 8. Andrieu, G., A.C. Belkina, and G.V. Denis, Clinical trials for BET inhibitors run ahead of the science.Drug Discov Today Technol, 2016. 19: p. 45-50. 9. Pervaiz, M., P. Mishra, and S. Gunther,Bromodomain Drug Discovery - the Past, the Present, and the Future.Chem Rec, 2018. 18(12): p. 1808-1817. Disclosures No relevant conflicts of interest to declare.

Circadian gene expression and extremely low-frequency magnetic fields: An in vitro study

2015 ◽  
Vol 36 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Nicola Manzella ◽  
Massimo Bracci ◽  
Veronica Ciarapica ◽  
Sara Staffolani ◽  
Elisabetta Strafella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Magnetic Fields ◽  
Low Frequency ◽  
In Vitro Study ◽  
Vitro Study ◽  
Circadian Gene ◽  
Extremely Low Frequency

scholarly journals Exposure to 50 Hz Extremely-Low-Frequency Magnetic Fields Induces No DNA Damage in Cells by Gamma H2AX Technology

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ye Lv ◽  
Shuchang Chen ◽  
Bing Zhu ◽  
Hong Xu ◽  
Shanshan Xu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Magnetic Fields ◽  
Umbilical Vein ◽  
Low Frequency ◽  
Systematic Research ◽  
Human Skin Fibroblast ◽  
Extremely Low Frequency ◽  
Γh2ax Foci ◽  
Significant Difference

The current results for extremely-low-frequency magnetic fields (ELF-MF) on DNA damage are still debated. A sensitive indicator and systematic research are needed to assess the effects of ELF-MF. In this study, we used γH2AX as an early and sensitive molecular marker to evaluate the DNA damage effects of ELF-MF in vitro. Human amnion epithelial cells (FLs), human skin fibroblast cells (HSFs), and human umbilical vein endothelial cells (HUVECs) were exposed to 50 Hz ELF-MF at 0.4, 1, and 2 mT for 15 min, 1 h, and 24 h, respectively. After exposure, cells were subjected to γH2AX immunofluorescence and western blot. The results showed no significant difference in the average number of foci per cell, the percentage of γH2AX foci-positive cells, or the expression of γH2AX between the sham and 50 Hz ELF-MF exposure groups ( P > 0.05 ). In conclusion, 50 Hz ELF-MF did not induce DNA damage in FLs, HSFs, or HUVECs, which was independent of the intensity or duration of the exposure.

scholarly journals Prospective pharmacological methodology for establishing and evaluating anti-cancer drug resistant cell lines

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hoon Yu ◽  
Dong-Jin Kim ◽  
Hye-Young Choi ◽  
So Myoung Kim ◽  
Md. Intazur Rahaman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Evaluation Methodology ◽  
Cross Resistance ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Resistance Evaluation ◽  
Cancer Drug Resistance ◽  
Anti Cancer

Abstract Background Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. Methods A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. Results It was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. Conclusion Since the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.

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