The effect of vinorelbine on hmg proteins in lung cancer a549 cells

Maryam Salarian ,1,* Azra rabbani-chadegani,2

Abstract


Introduction

Vinorelbine is a semisynthetic vinca alkaloid antitumor drug, widely used in the treatment of cancers such as advanced non-small cell lung cancer and breast cancer. its main mechanism of action is related to the inhibition of microtubule dynamics and interaction with chromatin and histone proteins, however, the effect on non-histone proteins such as hmgb1 which is an abundant non histone protein in chromatin structure is still unknown. this protein participate in processes such as replication, transcription, recombination, dna repair and inflammation.

Methods

Mtt assay, sds-page, western blot assay and acridine orange/ethidium bromide.

Results

. in the present study we have investigated the possible effects of vinorelbine on hmgb1 protein in a549 cells. the result obtained from mtt assay showed that vinorelbine decreased viability of a549 cells in a dose- and time- dependent manner with ic50 value of 4 µm after 48 hours of exposure. acridine orange/ethidium bromide staining of the drug treated cells revealed morphological changes such as chromatin condensation and nuclear fragmentation indicating occurrence of apoptosis and necrosis in these cells. the content of non-histone protein hmgb1 decreased on sds-gel upon increasing drug concentration and western blots against its specific antibody confirmed it. also, analysis of cell culture media after treatment of the cells revealed hmgb1 release into extracellular space confirming occurrence of apoptosis.

Conclusion

In conclusion, the results obtained from this study suggest that vinorelbine represents apoptotic and necrotic effects on a549 cells and hmgb1 protein plays an important role in this process.

Keywords

Vinorelbine, a549 lung cancer cells, hmgb1, apoptosis