Repair of interstrand DNA crosslinks induced by oxidative stress and anti-cancer agents

2019 ◽  
Vol 61 (4) ◽  
Author(s):  
U. Aliyaskarova ◽  
M. Saparbaev ◽  
Bissenbaev A
Keyword(s):  
Oxidative Stress ◽  
Dna Crosslinks ◽  
Anti Cancer

Synthesis and Anticancer Activity of 9-O-Pyrazole Alkyl Substituted Berberine Derivatives

2019 ◽  
Vol 18 (11) ◽  
pp. 1639-1648 ◽  
Author(s):  
Daipeng Xiao ◽  
Fen He ◽  
Dongming Peng ◽  
Min Zou ◽  
Junying Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Human Lung Cancer ◽  
Drug Candidate ◽  
Molecular Docking Study ◽  
Protective Function ◽  
Anti Cancer ◽  
Cancer Activity

Background: Berberine (BBR), an isoquinoline plant alkaloid isolated from plants such as Coptis chinensis and Hydrastis canadensis, own multiple pharmacological activities. Objective: In this study, seven BBR derivatives were synthesized and their anticancer activity against HeLa cervical and A549 human lung cancer cell lines were evaluated in vitro. Methods: The anti-cancer activity was measured by MTT assay, and apoptosis was demonstrated by the annexin V-FITC/PI staining assay. The intracellular oxidative stress was investigated through DCFH-DA assay. The molecular docking study was carried out in molecular operating environment (MOE). Results: Compound B3 and B5 showed enhanced anti-cancer activity compared with BBR, the IC50 for compound B3 and B5 were significantly lower than BBR, and compound B3 at the concentration of 64 or 128 µM induced apoptosis in HeLa and A549 cell lines. The reactive oxygen species (ROS) was generated in both cell lines when treated with 100 µM of all the compounds, and compound B3 and B5 induced higher activity in the generation of ROS, while compound B3 exhibited the highest activity, these results are in accordance with the cytotoxicity results, indicating the cytotoxicity were mostly generated from the oxidative stress. In addition, molecular docking analysis showed that compound B3 had the greatest affinity with Hsp90. Upon binding, the protective function of Hsp90 was lost, which might explain its higher cytotoxicity from molecular interaction aspect. Conclusion: All the results demonstrated that compound B3 and B5 showed significantly higher anti-cancer ability than BBR, and compound B3 is a promising anticancer drug candidate.

Natural-Derived Molecules as a Potential Adjuvant in Chemotherapy: Normal Cell Protectors and Cancer Cell Sensitizers

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Mohammad S. Mubarak ◽  
Divya Jain ◽  
Rasel Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Polyphenolic Compounds ◽  
Anticancer Effect ◽  
Anticancer Activities ◽  
Normal Cells ◽  
Anti Cancer ◽  
Global Threat

Background: Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. Objective: To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. Method: Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. Result: Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit ‎antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. Conclusions: Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.

scholarly journals Comprehensive analyses of the cysteine thiol oxidation of PKM2 reveal the effects of multiple oxidation on cellular oxidative stress response

2021 ◽  
Author(s):  
Hayato Irokawa ◽  
Satoshi Numasaki ◽  
Shin Kato ◽  
Kenta Iwai ◽  
Atsushi Inose-Maruyama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pyruvate Kinase ◽  
Redox Regulation ◽  
Cysteine Residue ◽  
Pentose Phosphate ◽  
Signal Pathways ◽  
Heterologous Proteins ◽  
Cancer Cell Growth ◽  
Anti Cancer ◽  
Cellular Signal

Redox regulation of proteins via cysteine residue oxidation is involved in the control of various cellular signal pathways. Pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, is critical for the metabolic shift from glycolysis to the pentose phosphate pathway under oxidative stress in cancer cell growth. The PKM2 tetramer is required for optimal pyruvate kinase (PK) activity, whereas the inhibition of inter-subunit interaction of PKM2 induced by Cys358 oxidation has reduced PK activity. In the present study, we identified three oxidation-sensitive cysteine residues (Cys358, Cys423 and Cys424) responsible for four oxidation forms via the thiol oxidant diamide and/or hydrogen peroxide (H2O2). Possibly due to obstruction of the dimer-dimer interface, H2O2-induced sulfenylation (-SOH) and diamide-induced modification at Cys424 inhibited tetramer formation and PK activity. Cys423 is responsible for intermolecular disulphide bonds with heterologous proteins via diamide. Additionally, intramolecular polysulphide linkage (–Sn–, n≧3) between Cys358 and an unidentified PKM2 Cys could be induced by diamide. We observed that cells expressing the oxidation-resistant PKM2 (PKM2C358,424A) produced more intracellular reactive oxygen species (ROS) and exhibited greater sensitivity to ROS-generating reagents and ROS-inducible anti-cancer drugs compared to cells expressing wildtype PKM2. These results highlight the possibility that PKM2 inhibition via Cys358 and Cys424 oxidation contributes to eliminating excess ROS and oxidative stress.

scholarly journals Pro-oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 532 ◽  
Author(s):  
Juhyun Shin ◽  
Min-Ho Song ◽  
Jae-Wook Oh ◽  
Young-Soo Keum ◽  
Ramesh Kumar Saini
Keyword(s):  
Oxidative Stress ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Research Gaps ◽  
Cytotoxic Effects ◽  
Normal Cells ◽  
Anti Cancer ◽  
Antioxidant Function ◽  
High Level ◽  
Β Carotene

Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, β-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.

scholarly journals Nestin regulates cellular redox homeostasis in lung cancer through the Keap1–Nrf2 feedback loop

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiancheng Wang ◽  
Qiying Lu ◽  
Jianye Cai ◽  
Yi Wang ◽  
Xiaofan Lai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Feedback Loop ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Cellular Redox ◽  
Anti Cancer ◽  
Oxidative Stress Status ◽  
Kelch Domain ◽  
Antioxidant Response Elements

Abstract Abnormal cancer antioxidant capacity is considered as a potential mechanism of tumor malignancy. Modulation of oxidative stress status is emerging as an anti-cancer treatment. Our previous studies have found that Nestin-knockdown cells were more sensitive to oxidative stress in non-small cell lung cancer (NSCLC). However, the molecular mechanism by which Nestin protects cells from oxidative damage remains unclear. Here, we identify a feedback loop between Nestin and Nrf2 maintaining the redox homeostasis. Mechanistically, the ESGE motif of Nestin interacts with the Kelch domain of Keap1 and competes with Nrf2 for Keap1 binding, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant enzyme generation. Interestingly, we also map that the antioxidant response elements (AREs) in the Nestin promoter are responsible for its induction via Nrf2. Taken together, our results indicate that the Nestin–Keap1–Nrf2 axis regulates cellular redox homeostasis and confers oxidative stress resistance in NSCLC.

scholarly journals Oxidative Stress Plays an Important Role in Zoledronic Acid-Induced Autophagy

2014 ◽  
pp. S601-S612 ◽  
Author(s):  
V. K. M. KHANDELWAL ◽  
L. M. MITROFAN ◽  
J. M. T. HYTTINEN ◽  
K. R. CHAUDHARI ◽  
R. BUCCIONE ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Mevalonate Pathway ◽  
Continuous Treatment ◽  
Autophagy Induction ◽  
Anti Cancer ◽  
Dose Dependent ◽  
And Oxidative Stress ◽  
Mcf 7

Several pre-clinical and clinical studies have demonstrated zoledronic acid (Zol), which regulates the mevalonate pathway, has efficient anti-cancer effects. Zol can also induce autophagy. The aim of this study is to add new understanding to the mechanism of autophagy induction by Zol. LC3B-II, the marker for autophagy was increased by Zol treatment in breast cancer cells. Autophagosomes induced by Zol were visualized and quantified in both transient (pDendra2-hLC3) and stable MCF-7-GFP-LC3 cell lines. Acidic vesicular organelles were quantified using acridine orange. Zol induced a dose and time dependent autophagy. Treatment of Zol increased oxidative stress in MCF-7 cells, which was reversed by GGOH or anti-oxidants. On the other hand, treatment with GGOH or anti-oxidants resulted in decreased levels of LC3B-II. Further, the induced autophagy was irreversible, as the washout of Zol after 2 h or 24 h resulted in similar levels of autophagy, as induced by continuous treatment after 72 h. Thus, it can be summarized that Zol can induce a dose dependent but irreversible autophagy, by its effect on the mevalonate pathway and oxidative stress. This study adds to the understanding of the mechanism of action of Zol, and that it can induce autophagy at clinically relevant shorter exposure times in cancer cells.

scholarly journals Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Khuloud Bajbouj ◽  
Lina Sahnoon ◽  
Jasmin Shafarin ◽  
Abeer Al-Ali ◽  
Jibran Sualeh Muhammad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Vitamin D ◽  
Breast Cancer Cells ◽  
Iron Homeostasis ◽  
Stress Induction ◽  
Protein Levels ◽  
Cellular Iron ◽  
Anti Cancer ◽  
Cellular Iron Homeostasis

Background: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remains ambiguous. Herein, we addressed whether vitamin D signaling exerts a role in cellular iron homeostasis thereby affecting survival of breast cancer cells.Methods: Expression profile of IRGs in vitamin D-treated breast cancer cells was analyzed using publicly available transcriptomic datasets. After treatment of BRCA cell lines MCF-7 and MDA-MB-231 with the active form of vitamin D, labile iron content, IRGs protein levels, oxidative stress, and cell survival were evaluated.Results: Bioinformatics analysis revealed several IRGs as well as cellular stress relates genes were differentially expressed in BRCA cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IRGs protein levels. Vitamin D treatment exerted oxidative stress induction and alteration in the cellular redox balance by increasing the synthesis of key stress-related markers. Collectively, these effects resulted in a significant decrease in BRCA cell survival.Conclusion: These findings suggest that vitamin D disrupts cellular iron homeostasis leading to oxidative stress induction and cell death.

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