Background: Despite a number of measures having been taken for cancer management, it is still the second
leading cause of death worldwide. p53 is the protein principally being targeted for cancer treatment. Targeting
p53 localization may be an effective strategy in chemotherapy as it controls major cell death pathways based on its
cellular localization. Anthraquinones are bioactive compounds widely being considered as potential anticancer agents
but their mechanism of action is yet to be explored. It has been shown that the number and position of hydroxyl
groups within the different anthraquinones like Emodin and Chrysophanol reflects the number of intermolecular
hydrogen bonds which affect its activity. Emodin contains an additional OH group at C-3, in comparison to Chrysophanol
and may differentially regulate different cell death pathways in cancer cell.
Objective: The present study was aimed to investigate the effect of two anthraquinones Emodin and Chrysophanol on
induction of different cell death pathways in human lung cancer cells (A549 cell line) and whether single OH group
difference between these compounds differentially regulate cell death pathways.
Methods: The cytotoxic effect of Emodin and Chrysophanol was determined by the MTT assay. The expression of autophagy
and apoptosis marker genes at mRNA and protein level after treatment was checked by the RT-PCR and Western
Blot, respectively. For cellular localization of p53 after treatment, we performed immunofluorescence microscopy.
Results: We observed that both compounds depicted a dose-dependent cytotoxic response in A549 cells which was
in concurrence with the markers associated with oxidative stress such as an increase in ROS generation, decrease in
MMP and DNA damage. We also observed that both compounds up-regulated the p53 expression where Emodin
causes nuclear p53 localization, which leads to down-regulation in mTOR expression and induces autophagy while
Chrysophanol inhibits p53 translocation into nucleus, up-regulates mTOR expression and inhibits autophagy.
Conclusion: From this study, it may be concluded that the structural difference of single hydroxyl group may switch
the mechanism from one pathway to another which could be useful in the future to improve anticancer treatment and
help in the development of new selective therapies.