Synergistic therapeutic effect of nano-honokiol and 5-fluorouracil on the induced-tongue cancer in rats

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© 2020 Asian AOMS(+) ASOMP(+) JSOP(+) JSOMS(+) JSOM(+) and JAMI Objectives: This research aims to investigate the effect of combining 5-FU with honokiol-nanoparticles (HNK-NP) on enhancing the anti-cancerous activity of 5-FU without intensifying its toxicity to normal tissues. Material and methods: Honokiol (HNK) was formulated in nano-particles (HNK-NPs) for better bioavailability, efficient penetration, and sustained release. HNK-NPs were successfully prepared using the nano-precipitation technique and evaluated using the transmission electron microscope (TEM). It was used in combination with 5-FU for treatment of tongue carcinoma-induced chemically by 4-nitroquinoline oxide (4NQO) in Wistar albino rats. They were divided into five groups (10 animals each) including untreated control, 4NQO, 5-FU, HNK-NPs, and 5-FU with HNK-NPs. Assessment of liver enzymes and creatinine was done to evaluate the safety of the used drugs. Serial sections of the tongues were examined histologically, immunohistochemical (IHC) detection of the P53 protein, and real-time PCR (polymerase chain reaction) of P53 gene expression were also assessed. Results: The results showed that treatment with both 5-FU + HNK-NPs had significantly regressed tumors induced by the carcinogen, with a marked reduction in the systemic toxicity as compared with either drug individually. Data analysis showed statistically significant differences (P < 0.05) in the expression levels of P53 either through IHC or molecular detection between the combined treatment and positive control groups. Conclusion: The combination therapy including 5-FU and HNK-NPs has substantial potential as an anti-cancer chemotherapeutic strategy.

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