The Risk of Flavonoids Utilization in the Anti-Tumor Therapy

Food and Drug Administration (FDA) remains to pay much caution to approve flavonoids as clinical drugs. The present study aims to investigate the potential influence of flavonoids apigenin and kaempferol towards the toxicity of irinotecan. For irinotecan-induced diarrhea model, intraperitoneal injection (i.p.) of 50 mg/kg body weight of irinotecan was performed for 3 days. For the protection role of apigenin and kaempferol, 500 mg/kg body weight of apigenin or kaempferol was given through intraperitoneal injection (i.p.) for 30 days before the administration of irinotecan. The body weight was monitored daily during the treatment of irinotecan. The treatment with irinotecan (50 mg/kg, i.p.) for 3 days did not induce the significant decrease of body weight. The pre-treatment of apigenin or kaempferol (500 mg/kg, i.p.) can significantly strengthen irinotecan-induced toxicity, as indicated by the increased body weight loss in comparison with irinotecan-treatment group. Furthermore, the mechanisms were elucidated from the following reasons: 1) The pre-treatment of apigenin or kaempferol significantly inhibited the expression of UGT1A1, indicated by the decreased level of ugt1a1 mRNA. 2) Apigenin or kaempferol significantly inhibited glucuronidation metabolism of SN-38 which is the active metabolite of irinotecan. In conclusion, the utilization risk of flavonoids in the anti-tumor utilization was demonstrated in the present study. All these results provide a caution for approving the flavonoids as the clinical drugs.