Oxidative stress-induced cardiomyocyte apoptosis is associated with dysregulated Akt/p53 signaling pathway

Background: Cancer is characterized by overexpression of p53 associated proteins, which down-regulate P53 signaling pathway. In cancer therapy, p53 activity can be restored by inhibiting the interaction of MDMX (2N0W) and MDM2 (4JGR) proteins with P53 protein. Objective: In the current, study in silico approaches were adapted to use a natural product as a source of cancer therapy. Methods: In the current study in silico approaches were adapted to use a natural product as a source of cancer therapy. For in silico studies, Chemdraw and Molecular Operating Environment were used for structure drawing and molecular docking, respectively. Flavonoids isolated from D. carota were docked with cancerous proteins. Result: Based on the docking score analysis, we found that compound 7 was the potent inhibitor of both cancerous proteins and can be used as a potent molecule for inhibition of 2N0W and 4JGR interaction with p53. Conclusion: Thus the compound 7 can be used for the revival of p53 signaling pathway function however, intensive in vitro and in vivo experiments are required to prove the in silico analysis.

Download Full-text

Novel β-Carboline/Hydroxamic Acid Hybrids Targeting Both Histone Deacetylase and DNA Display High Anticancer Activity via Regulation of the p53 Signaling Pathway

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.5b01052 ◽

2015 ◽

Vol 58 (23) ◽

pp. 9214-9227 ◽

Cited By ~ 36

Author(s):

Yong Ling ◽

Chenjun Xu ◽

Lin Luo ◽

Jingyi Cao ◽

Jiao Feng ◽

...

Keyword(s):

Anticancer Activity ◽

Signaling Pathway ◽

Histone Deacetylase ◽

Hydroxamic Acid ◽

P53 Signaling ◽

P53 Signaling Pathway

Download Full-text

Combining targeted therapies with HDAC inhibitors to tackle the p53 signaling pathway in hepatocellular carcinoma

10.1055/s-0040-1722065 ◽

2021 ◽

Author(s):

L Brandes ◽

E Aschenbrenner ◽

K Pollinger ◽

K Gülow ◽

C Kunst ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Targeted Therapies ◽

Hdac Inhibitors ◽

P53 Signaling ◽

P53 Signaling Pathway

Download Full-text

Akt Inhibition Enhanced the Growth Inhibition Effects of Low-Dose Heavy-Ion Radiation via the PI3K/Akt/p53 Signaling Pathway in C6 Glioblastoma Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.649176 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ke Huang ◽

Wei Zhao ◽

Xuqiao Wang ◽

Yingfei Qiu ◽

Zelin Liu ◽

...

Keyword(s):

Growth Inhibition ◽

Signaling Pathway ◽

Low Dose ◽

Ion Irradiation ◽

Heavy Ion ◽

C6 Cells ◽

Carbon Ion ◽

P53 Signaling ◽

Heavy Ion Radiation ◽

P53 Signaling Pathway

BackgroundGlioma has one of the highest mortality rates of all tumors of the nervous system and commonly used treatments almost always fail to achieve tumor control. Low-dose carbon-ion radiation can effectively target cancer and tumor cells, but the mechanisms of growth inhibition induced by heavy-ion radiation via the PI3K/Akt signaling pathway are unknown, and inhibition by heavy-ion radiation is minor in C6 cells.MethodsCarbon-ion radiation was used to investigate the effects of heavy-ion radiation on C6 cells, and suppression of Akt was performed using perifosine. MTT assays were used to investigate optimal perifosine treatment concentrations. Clone formation assays were used to investigate the growth inhibition effects of carbon-ion radiation and the effects of radiation with Akt inhibition. Lactate dehydrogenase release, superoxide dismutase activity, and malondialdehyde content were assessed to investigate oxidative stress levels. Expression levels of proteins in the PI3K/Akt/p53 signaling pathway were assessed via western blotting.ResultsThe 10% maximum inhibitory concentration of perifosine was 19.95 μM. In clone formation assays there was no significant inhibition of cell growth after treatment with heavy-ion irradiation, whereas perifosine enhanced inhibition. Heavy-ion radiation induced lactate dehydrogenase release, increased the level of malondialdehyde, and reduced superoxide dismutase activity. Akt inhibition promoted these processes. Heavy-ion radiation treatment downregulated Akt expression, and upregulated B-cell lymphoma-2 (Bcl-2) expression. p53 and Bcl-2 expression were significantly upregulated, and Bcl-2-associated X protein (Bax) expression was downregulated. The expression profiles of pAkt, Bcl-2, and Bax were reversed by perifosine treatment. Caspase 3 expression was upregulated in all radiation groups.ConclusionsThe growth inhibition effects of low-dose heavy-ion irradiation were not substantial in C6 cells, and Akt inhibition induced by perifosine enhanced the growth inhibition effects via proliferation inhibition, apoptosis, and oxidative stress. Akt inhibition enhanced the effects of heavy-ion radiation, and the PI3K/Akt/p53 signaling pathway may be a critical component involved in the process.

Download Full-text