scholarly journals In Vitro Molecular Biology Studies of Spirooxindole Heterocyclic Hybrids

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1473
Author(s):  
Dhaifallah M. Al-thamili ◽  
Abdulrahman I. Almansour ◽  
Natarajan Arumugam ◽  
Faruq Mohammad ◽  
Raju Suresh Kumar

 In the present report, we provide the results of the molecular biology studies of spiroheterocyclic hybrids, where the derivatives are found to possess potential anticancer activity towards cancer cells. A series of spiroxindole–pyrrolidine heterocyclic hybrids were evaluated for cell viability and proliferation against HepG2 cancer cells at concentrations in the range of 12.5–200 µg/mL over two different time periods of 24 and 48 h. In addition, the highly active compounds were also verified for their behavior towards noncancer cells (L929 cells), and it was found that the tested derivatives were not aggressive due to the observation of only limited cell loss, as compared to the cancer cells. Further analysis of the observed toxicity mechanism showed the apoptotic pathway was mediated by oxidative stress, with the involvement of caspases.

2020 ◽  
Vol 17 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Xuan Chen ◽  
Sumei Zhang ◽  
Peipei Shi ◽  
Yangli Su ◽  
Dong Zhang ◽  
...  

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.


Author(s):  
MOUNICA RAJU DANTULURI ◽  
ANIMISHA MOKKAPATI ◽  
RADHAKRISHNA NAGUMANTRI ◽  
SATYANARAYANA RENTALA

2010 ◽  
Vol 43 (10) ◽  
pp. 1001-1009 ◽  
Author(s):  
A.O. Santos ◽  
J.P. Pereira ◽  
M.C. Pedroso de Lima ◽  
S. Simões ◽  
J.N. Moreira

2006 ◽  
Vol 25 (6) ◽  
pp. 451-457 ◽  
Author(s):  
Weisheng Lin ◽  
Yue-wern Huang ◽  
Xiao-Dong Zhou ◽  
Yinfa Ma

With the fast development of nanotechnology, the nanomaterials start to cause people’s attention for potential toxic effect. In this paper, the cytotoxicity and oxidative stress caused by 20-nm cerium oxide (CeO2) nanoparticles in cultured human lung cancer cells was investigated. The sulforhodamine B method was employed to assess cell viability after exposure to 3.5, 10.5, and 23.3 μg/ml of CeO2 nanoparticles for 24, 48, and 72 h. Cell viability decreased significantly as a function of nanoparticle dose and exposure time. Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species, glutathione, malondialdehyde, α-tocopherol, and lactate dehydrogenase, were quantitatively assessed. It is concluded from the results that free radicals generated by exposure to 3.5 to 23.3 μg/ml CeO2 nanoparticles produce significant oxidative stress in the cells, as reflected by reduced glutathione and α-tocopherol levels; the toxic effects of CeO2 nanoparticles are dose dependent and time dependent; elevated oxidative stress increases the production of malondialdehyde and lactate dehydrogenase, which are indicators of lipid peroxidation and cell membrane damage, respectively.


Author(s):  
Joel Hillelsohn ◽  
Michael Stern ◽  
Mina Iskander ◽  
Muhammad Choudhury ◽  
Sensuke Konno

Background: Despite several therapeutic options available for bladder cancer, the outcomes are less satisfactory.  To find a more effective modality, we were interested in the bioactive mushroom extract, PDF, which has been shown to sensitize certain anticancer drugs.  Accordingly, we investigated if cytotoxic effects of several anticancer drugs used on bladder cancer patients could be enhanced with PDF in vitro.Methods: Human bladder cancer T24 cells were treated with four anticancer drugs, carmustine (BCNU), 5-fluorouracil (5FU), cisplatin (CPL), and doxorubicin (DOX) alone, their combinations, or in combination with PDF, and cell viability was determined.  To explore the anticancer mechanism, the status of glyoxalase I (Gly-I), an enzyme involved in the drug resistance of cancer cells, and oxidative stress that can cause severe cellular injury/damage was also assessed.Results: BCNU and 5FU alone resulted in a >50% reduction in cell viability but CPL and DOX had no such effects.  Only a combination of BCNU and PDF led to a drastic (~90%) cell viability reduction, accompanied by inactivation of Gly-I and an increase in oxidative stress.  However, any combinations of other drugs and PDF had little effects on cell viability, Gly-I activity, or severity of oxidative stress.Conclusions: This study shows that anticancer activity of BCNU is significantly potentiated with PDF in T24 cells.  This is rather attributed to inactivated Gly-I and increased oxidative stress.  Therefore, PDF appears to have a chemosensitizing effect capable of enhancing BCNU cytotoxicity, which may offer an alternative, improved therapeutic option for bladder cancer.


2022 ◽  
Author(s):  
Ahmed K. Abogosh ◽  
Meshal Alghanem ◽  
Saeed Ahmad ◽  
Abdullah Alasmari ◽  
Homood M. As Sobeai ◽  
...  

A new dinuclear cyclic gold(I) complex [Au2(DCyPA)2](PF6)2, 1 based on bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA) has been synthesized and characterized by elemental analysis, IR and NMR spectroscopies, and X-ray crystallography. In the dinuclear...


2021 ◽  
Author(s):  
Yajun Chen ◽  
Lei Wang ◽  
Tianjia Liu ◽  
Zhidong Qiu ◽  
Ye Qiu ◽  
...  

We investigated the protective effect of PGP against DOX-induced cardiotoxicity in vitro and in vivo. PGP increases H9C2 cell viability and inhibits apoptosis, alleviating DOX-induced myocardial oxidative stress-related cardiotoxicity.


Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1154 ◽  
Author(s):  
Dhaifallah M. Al-thamili ◽  
Abdulrahman I. Almansour ◽  
Natarajan Arumugam ◽  
Faruq Mohammad ◽  
Raju Suresh Kumar

Structurally interesting N-pyridinylmethyl engrafted bisarylmethylidenepyridinones with high functionality have been constructed in good yield. The structural interpretation of these compounds has been done with the aid of spectroscopic analysis and further established by single crystal X-ray diffraction studies. Following physical characterization, the synthesized compounds were tested for their in vitro anticancer activity against HepG2 cancer cells and it was found that all of the compounds exhibited some level of activity. We observed a significant level of cell viability losses to the cancer cells, while only smaller losses to the non-cancer cells were observed. Besides, the mechanistic investigation of toxicology revealed that the cancer cells were undergoing apoptotic pathway, induced by the generation of oxidative stress and the involvement of caspases. The analysis provides preliminary evidence for the successful control of cancer cells with a minimal effect on healthy normal cells because of the high IC50 levels and cell death mechanisms.


2020 ◽  
Vol 40 (6) ◽  
pp. 737-747
Author(s):  
Agnieszka Ścibior ◽  
Konrad A. Szychowski ◽  
Iwona Zwolak ◽  
Klaudia Dachowska ◽  
Jan Gmiński

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Meng-Hsuan Cheng ◽  
Hung-Ling Huang ◽  
Yen-You Lin ◽  
Kuan-Hao Tsui ◽  
Pei-Chin Chen ◽  
...  

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.


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