Possible Interaction: Proanthocyanidin and Doxorubicin Hydrochloride

“A combination of PA 12.5, 25 mg/l with DOX 0.01 approximately 1 mg/l treatment synergistically inhibited proliferation of K562, A549, and CNE cells with decreased IC50 values.”

“At the same time, K562 … apoptosis following treatment with PA … DOX , and the administration of PA 25 mg/l plus DOX 0.3 mg/l for 24 h resulted in … the percentage of apoptosis by flow cytometry as compared with DOX 0.3 mg/l alone (p < 0.05).”

“Under the confocal laser scanning microscope, intracellular DOX, Ca2+, and Mg2+ concentrations were greatly increased whereas pH value and mitochondrial membrane potential were markedly reduced in K562 cells after treatment with a combination of PA plus DOX.”

“A combination of proanthocyani din 12.5, or 25 mg/L and doxorubicin treatment synergistically inhibited cell proliferation with decreased IC50 values.”

“These results suggest that proanthocyanidin enhances doxorubicin-induced antitumor effect and reverses drug resistance, and its mechanism is attributed partially to the promotion of doxorubicin-induced apoptosis through an elevation of intracellular doxorubicin, and Ca2+, Mg2+ concentration, and a reduction of pH value and mitochondrial membrane potential.”

“Under confocal laser scanning …, the combination of proanthocyanidin 25 or 50 mg/L with doxorubicin 3 mg/L significantly increased the accumulation of intracellular doxorubicin, Ca2+, and Mg2+, and reduced the pH value and mitochondrial membrane potential in K562/DOX cells as compared with doxorubicin alone (p < 0.01).”

“With the aim of enhancing the efficacy of chemotherapeutic agents, we investigated the antitumor actions and reversal effect on drug resistance of proanthocyanidin plus doxorubicin.”

“administration of proanthocyanidin 10 mg/kg with doxorubicin 2 mg/kg had an inhibitory effect on the growth of transplantation tumor sarcoma 180 and hepatoma 22 in mice as compared with doxorubicin alone (p < 0.05).”

“CK levels were elevated after DXR administration, indicating myocardial injury, but PA significantly reversed this.”

“ DXR treatment decreased CAT enzyme levels, but additional PA and hazelnut consumption increased these levels at low cumulative doses.”

“ PA prevented the decrease at low doses of DXR.”

“In conclusion, intragastric administration of proanthocyanidin could enhance the anti‐tumour activity of doxorubicin and ameliorate doxorubicin‐induced myocardial oxidative stress and immunosuppression in tumour‐bearing mice.”

“Moreover, proanthocyanidin strongly enhanced the anti‐tumour effect of doxorubicin and the above immune responses, and completely eliminated myocardial oxidative stress induced by doxorubicin.”

“In contrast to PA treatment, DOX inhibited Con A-stimulated lymphocyte proliferation, IL-2 and IFN-gamma productions, NK cell cytotoxicity and CD4+/CD8+ ratio, while the administration of PA combined with DOX significantly enhanced the above immune responses as compared with the tumor-bearing control (p<0.01).”

“Meanwhile, a combination of PA (12.5, 25 mg/l) with DOX strongly inhibited cell proliferation with IC(50) values of DOX decreasing by 0.09 and 0.045 mg/l, respectively.”

“Taken together, these results suggest that PA has anti-tumor activity and increases the anti-tumor activity of DOX , and the mechanism might be related partially to immunopotentiating activities through the enhancements of lymphocyte proliferation, NK cell cytotoxicity, CD4+/CD8+ ratio, IL-2 and IFN-gamma productions.”