Background: Cancer being a genetically heterogeneous and complex disease and the available therapies
are not very effective, rendering them the predominant cause of mortality across the world. The discovery
of new anticancer drugs with higher efficacy and milder side effects is a great challenge for health professionals.
Objective: The current study focused on the anticancer potential of two known dimeric napthoquiones,
diospyrin (1) and 8-hydroxydiospyrin (2) isolated from the roots of Diospyros lotus.
Methods: In-vitro Epstein-Barr-Virus (EVA) an early antigen activation assay was used to evaluate the antitumor
potential of tested compounds followed by a two-stage carcinogenesis assay on mouse skin for anti-carcinogenic
effect. Compounds were also assessed for their multidrug resistance reversal potential. The in-vitro heatinduced
protein denaturation assay was used for the anti-inflammatory effect of the tested compounds.
Results: Both compounds evoked marked cytotoxic activity with IC50 of 47.40 and 36.91 ppm, respectively. In
Epstein-Barr-Virus (EVA) early antigen activation assay compounds 1 and 2 showed IC50 values of 426 ppm
and 412 ppm, respectively. The tested compounds showed 60% survival rate of the lymphoblastoid Raji cells at
a concentration of 1000 (mol / ratio 32 pmol TPA). In a two-stage carcinogenesis assay on mouse skin, both
compounds significantly delayed the formation of papillomas on mouse skin. Compound 1 showed 50% effect
at 14th week, whereas compound 2 exerted the same effect at 13th week, while both provoked 100% effect at
20th week. Both compounds significantly attenuated thermal-induced protein denaturation with EC50 values of
298 and 264 μg/mL, respectively. The dimeric napthoquiones were evaluated for their effects on the reversion
of multidrug-resistant (MDR) cell lines mediated by P-glycoprotein using rhodamine 123 dye-based exclusion
screening test on human mdr1 gene transfected thymic lymphoma L5178 cell line. The compounds 1 and 2 exhibited
promising MDR reversal effect in a dose-dependent manner against mouse T-lymphoma cell line. Docking
results also showed that both compounds have good docking statistics as compared with standard.
Conclusion: Both the compounds demonstrated marked anti-tumor, anti-carcinogenic, and MDR reversal effects
with significant attenuation of thermal-induced denaturation of the protein. These compounds may explain
the traditional uses of D. lotus which might be effective anticancer agents.