Green tea, red wine and lemon extracts reduce experimental tumor growth and cancer drug toxicity

Abstract

Aim: To evaluate antitumor effect of plant polyphenol extracts from green tea, red wine lees and/or lemon peel alone and in combination with antitumor drugs on the growth of different transplanted tumors in experimental animals. Materials and Methods: Green tea extract (GTE) was prepared from green tea infusion. GTE-based composites of red wine (GTRW), lemon peel (GTRWL) and/or NanoGTE as well as corresponding nanocomposites were prepared. The total polyphenolics of the different GTE-based extracts ranged from 18.0% to 21.3%. The effects of GTE-based extracts were studied in sarcoma 180, Ehrlich carcinoma, B16 melanoma, Ca755 mammary carcinoma, P388 leukemia, L1210 leukemia, and Guerin carcinoma (original, cisplatin-resistant and doxorubicin-resistant variants). The extracts were administered as 0.1% solution in drinking water (0.6–1.0 mg by total polyphenolics per mouse per day and 4.0–6.3 mg per rat per day). Results: Tumor growth inhibition (TGI) in mice treated with NanoGTE, cisplatin or cisplatin + NanoGTE was 27%, 55% and 78%, respectively, in Sarcoma 180%, 21%, 45% and 59%, respectively, in Ehrlich carcinoma; and 8%, 13% and 38%, respectively in B16 melanoma. Composites of NanoGTE, red wine, and lemon peel (NanoGTRWL) enhanced the antitumor effects of cyclophosphamide in mice with Ca755 mammary carcinoma. The treatment with combination of NanoGTE and inhibitors of polyamines (PA) synthesis (DFMO + MGBG) resulted in significant TGI of P388 leukemia (up to 71%) and L1210 leukemia. In rats transplanted with Guerin carcinoma (parental strain), treatment with GTRW or GTE alone resulted in 25–28% TGI vs. 55–68% TGI in cisplatin-treated animals. The inhibition observed in the case of combination of GTE or GTRW with cisplatin was additive giving 81–88% TGI. Similar effects were observed when combinations of the cytostatics with GTE (or ­NanoGTE) were tested against cisplatin- or doxorubicin-resistant Guerin carcinoma. Moreover, the plant extracts lowered side toxicity of the drugs. Treatment with GTE, NanoGTE, and NanoGTRW decreased the levels of malondialdehyde in heart, kidney and liver tissue of experimental animals, as well as the levels of urea and creatinine in blood serum, increased erythrocyte and platelet counts, hemoglobin content, and decreased leucocyte counts. Conclusion: The obtained data indicate the prospects for further deve­lopment of GTE and corresponding nanocomposites as auxiliary agents in cancer chemotherapy. Key Words: polyphenolic plant extracts, antitumor effect, cancer therapy.