Cytotoxic effects and expressional modifications induced by alkyl-phospholipid (erufosine) in lung cancer cells

Abstract

Background Lung cancer is the leading cause of morbidity and mortality in the world. Treatment of lung cancer is a challenge because of the aggressive nature of this disease and limited therapeutic options. The situation demands to investigate novel compounds for better treatment of lung cancer with lesser side effects. Alkyl-phospholipids (ALPs) are an attractive class of antineoplastic agents which target DNA and act upon cell membranes to produce anticancer effects in tumour cell specific manners. Erufosine is the 3^rd generation ALP and induces anticancer effects by causing changes in the lipid rafts of the cell membrane.

Methods: Selected lung cancer cell line (H1299) was cultured in 96-well plates and exposed to various concentrations of Erufosine (1.56-50µM) followed by MTT dye-based assessment of viable cell fractions. For expression modifications, the cells were exposed to Erufosine followed by RNA extraction, cDNA synthesis and real-time PCR based assessment of the selected genes modulations.

Results: Erufosine induced substantial cytotoxic effects in the lung cancer cells as shown by growth inhibition of 25 and 50% by using 24 and 33µM concentration respectively. At lower concentrations (6.25µM), there were negligible cytotoxic effects, which gradually increased with increasing concentrations. As far as expressional changes are concerned, the three selected genes (CCNB1, CDKN3, CASP3) were down-regulated in response to Erufosine exposure.

Conclusion Erufosine is a potential cytotoxic compound, induces notable anti-proliferative effects and modulate expressional levels of the genes in lung cancer cells.