44 2033180199

Phospholipase A2 isoforms in benzo (α) pyrene-induced molecular changes in colon cancer cells: A plausible therapeutic target

Sanjeev Kumar Sharma, Subodh Kumar Yadav, Ujjawal Sharma, Pramod Avti, SatyatiVati Rana, Krishan Lal Khanduja

INTRODUCTION: Colorectal cancer is the third most common cancer prevalent in men, and the second in women worldwide. The exact cause and pathogenesis of this disease remains unknown. In every cell multiple Phospholipase A2 (PLA2) exists, but their contribution to the cell function has yet not been determined. This study has explored the pathways involved in the differential response of HCT-15 and HT-29 colon cell lines during benzo(α)pyrene [B(α)P]-induced molecular changes.

METHODS: B(α)P]-induced molecular changes were evaluated through cell viability using MTT assay, Reactive Oxygen Species (ROS) measurement. The gene expressions of PLA2 isoforms were estimated by RT- PCR. Further, knockdown of PLA2 isoform in transfected cells was done with siRNA.

RESULTS: The cell viability decreased whereas ROS production increased significantly after exposure with B(α)P in both cell lines. Three PLA2 isoforms such as IB and, IID, IVA were induced after exposure with B(α)P respectively in HT -29 and HCT-15 cell lines. There was a significant induction of ROS in IVA transfected HCT-15 cells exposure with B(α)P.

DISCUSSION: CS continues to remain one of the most important health hazards and it contributes extensively too many diseases including respiratory disorders characterized by inflammatory changes in the lungs. It is involved in many other cancers like pharynx, larynx, esophagus, etc. various studies also suggested the relationship between smoking and stomach, liver and colon cancer.

CONCLUSION: It is concluded that each cell line behaved differently, specific PLA2 siRNA are involved in controlling the cascades related ROS, depending upon the origin of the cells. Secretary Phospholipase A2 inhibitors are likely to have a therapeutic potential in colon pathologies.

 


 
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