Effect of butein and glucose on oxidative stress and p38 activation marker in non-small cell lung cancer cell.

Abstract

INTRODUCTION:

Tumor microenvironment is known to alter the anticancer drug efficiency. One of the factors that get altered in cancer microenvironment is glucose concentration. Butein, an active principle from plant, known to have anticancer effect against different types of tumor. The objective of the study is to determine the effect of butein on glucose exposed non-small cell lung cancer cells (NSCLCCs).

METHODS:

The current study deals with the effect of butein (6.25-50μM) on NSCLCCs treated with different concentrations (0-40 mM) of glucose.

RESULTS AND DISCUSSION:

Glucose concentration, 0 mM and 40 mM, was found to be lethal at 72 h. Viable cell numbers were statistically increased in 5-mM, 10-mM, and 20-mM glucose-treated cells. Butein at 12.5 µM inhibits (p < 0.05) glucose-induced cell proliferation. Butein inhibits glucose-induced proliferation through DNA damage and oxidative stress. Mitochondrial reactive oxygen species (ROS) level was elevated in 20-mM glucose-treated cells when compared to 5-mM glucose-treated cells, whereas butein treatment further increases glucose-induced mitochondrial ROS. Pharmacological inhibitor of glycolysis, such as 2-deoxy glucose (2-DG), was found to inhibit (p < 0.05) glucose-induced cells proliferation. Furthermore, 2-DG and butein showed synergistic anticancer effect. Butein treatment increases p38 phosphorylation. Inhibition of p38 phosphorylation and antioxidant pretreatment partially revert the glucose-induced cell proliferation. However, inhibition of p38 phosphorylation combined with antioxidant pretreatment completely reverts the anticancer effect of butein. The present study concludes through the evidence that butein could serve as a potential anticancer compound in tumor microenvironment.

• Authors: C Zhang, X Zong, Y Han
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 38 Issue 10 Pg. 1155-1167 (Oct 2019) ISSN: 1477-0903 [Electronic] England
• PMID: 31215238 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Chalcones
• Reactive Oxygen Species
• butein
• p38 Mitogen-Activated Protein Kinases
• Glucose

Topics

• A549 Cells
• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma, Non-Small-Cell Lung (metabolism)
• Cell Survival (drug effects)
• Chalcones (pharmacology)
• Cytosol (drug effects, metabolism)
• DNA Damage
• Dose-Response Relationship, Drug
• Glucose (pharmacology)
• Humans
• Lung Neoplasms (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Tumor Microenvironment (drug effects, genetics)
• p38 Mitogen-Activated Protein Kinases (metabolism)