Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats

ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO). MATERIALS AND METHODS: Seven groups of Sprague–Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment. RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-β) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone. CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-β signaling axis.