Possible Interaction: Quercetin and Doxorubicin Hydrochloride

“Compared with adriamycin group, the SOD activity in adriamycin combined with quercetin group increased significantly and the MDA content decreased.”

“ Quercetin combined with adriamycin inhibit the proliferation of primary leukemia cells significantly, and had synergistic and additive effects on the proliferation of primary leukemia cells, and the inhibiting effect of quercetin combined with adriamycin is concentration-and time-dependent.”

“ Quercetin combined with high-dose adriamycin can significantly prolong the survival time of non-irradiated T-ALL leukemia mice and reduce the myocardial damage caused by adriamycin.”

“The survival time of non-irradiated T-ALL leukemia mice treated with high dose of adriamycin and quercetin was significantly prolonged (P＜0.05).”

“More importantly, our results revealed that enhanced anticancer efficacy was achieved through the combination of Que and Dox via the tumor microenvironment remodeling effect of Que to potentiate drug penetration into deep tumor tissues.”

“Furthermore, QUR did not interfere but rather enhanced the cytotoxic effects of DOX on different human cancer cell lines.”

“Que could sensitize the anti-leukemic effect of ADM by inhibiting the proliferation of white blood cells through trapping the cells …; caspase-3 was activated via the expressional regulation of Bcl-2, Bax, and NF-κB. When applied in combination with ADM, Que could attenuate heart … reactive oxygen species.”

“Results Compared with ADM group, the combination of ADM and Que showed prolonged survival time and less peripheral white blood cells.”

“ DR reduced the glomerular filtration rate to 25.2 vs RT, 48 ± 11.3; QT , 124.7 ± 12.8 (p < 0.001) and the control, 191.5 ± 15.7 mL/h (p < 0.001).”

“Conclusion and Significance These results indicate that quercetin potentiated the antitumor effects of DOX on liver cancer cells while protecting normal liver cells.”

“The combined treatment of quercetin and DOX significantly reduced the growth of liver cancer xenografts in mice.”

“Therefore, the development of quercetin may be beneficial in a combined treatment with DOX for increased therapeutic efficacy against liver cancer.”

“Compared to control, quercetin significantly (p < 0.05 for 0.6 mg/kg, p < 0.01 for 3 and 15 mg/kg) increased the area under the plasma concentration-time curve (AUC0−∞, 31.2-136.0% greater) of oral doxorubicin.”

“Consequently, the absolute bioavailability of doxorubicin was increased by quercetin compared to control, and the relative bioavailability of oral doxorubicin was increased by 1.32 to 2.36 fold.”

“ Quercetin also significantly increased the peak plasma concentration (Cmax) of doxorubicin , while there was no significant change in Tmax and T1/2 of doxorubicin.”

“Therefore, concurrent use of quercetin provides a therapeutic benefit — it increases the bioavailability of doxorubicin administered orally.”

“Thus, it is expected that the pharmacokinetics of both intravenous and oral doxorubicin can be changed by quercetin.”

“Interestingly, dietary quercetin combining intratumoral doxorubicin injection synergistically induced potent rejection of 4T1 breast cancer and led to long-term, tumor-free survival in mice bearing established breast tumor, whereas quercetin or doxorubicin alone failed to cure tumor-bearing mice.”

“In addition, doxorubicin incubation increased reactive oxygen species generation from the isolated aorta, while coincubation with quercetin inhibited ROS generation back to normal values.”

“In conclusion, quercetin , despite its potent vascular protective activity against doxorubicin, was found to influence doxorubicin-induced antibreast cancer effects via pharmacodynamic as well as cellular pharmacokinetic aspects.”

“Interestingly, quercetin was found to inhibit the P-glycoprotein ATPase subunit with a consequent enhanced intracellular concentration of doxorubicin in MDA-MB-231 and T47D cells.”

“Only in T47D cells, quercetin combination with doxorubicin was an additive interaction (CI − value = 1.17).”

“These findings indicate a significant antagonistic interaction between quercetin and doxorubicin in the aforementioned cell lines.”

“Yet, quercetin significantly impaired the immediate phase of intracellular ROS generation by doxorubicin within breast cancer cells from 125.2 ± 3.6% to 102.5 ± 3.9% of control cells.”

“Further mechanism studies demonstrated that Que inhibited the ATP-driven transport activity of P-gp, which in turn increased the intracellular accumulation of Dox.”

“Our present results showed that 33 μM of Que significantly improved the cytotoxicity of doxorubicin ( Dox ) to P-gp-overexpressed SW620/Ad300 cells by proliferation and apoptpsis assay.”