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3 . 2021

Evaluation of the chemopreventive potential of polyprenols from the needles of Picea abies L. and Pinus sylvestris L. using the model of prostate carcinogenesis in male Wistar rats

Abstract

For decades, one of the most popular ideas in reducing the burden of cancer worldwide is the idea of cancer chemoprevention with low-toxic agents. There is an evidence that polyprenols (polyisoprenoid alcohols) are perspective agents for cancer chemoprevention. The aim of the study is to investigate anticancer activity of the polyprenol complex (the main polyprenols are prenol-14, prenol-15, prenol-16 and prenol-17) against prostate cancer (PCa) and its precursor (prostatic intraepithelial neoplasia, PIN).

Material and methods. For induction of prostate carcinogenesis we used modified protocol of two-stage model. Mature male Wistar rats were administrated with single intravenous injection of N-methyl-N-nitrosourea and chronic intraperitoneal injections of four testosterone esters following surgical castration. Animals with an initial body weight of328+39 g were randomized into 3 groups: experimental group (n=32) - animals received polyprenols complex 12.5 mg/kg per os diluted in vegetable oil 5 days a week; control group (n=38) - animals received vehicle (vegetable oil) 0.5 ml per os 5 days a week; intact group (n=12) - animals without intervention. Duration of the experiment was 56 weeks. At the end of the study and in euthanized animals in terminal state as well, the prostate and seminal vesicles were processed by histological technique and serial step sections of all lobes were assessed blindly by two independent pathologists. Incidence and multiplicity of precancerous lesion (PIN) and prostate tumors were calculated.

Results. Compared with the control group, long-term consumption of polyprenols significantly reduced the overall incidence of PIN from 76.5 to 44.8% (р=0.0183; relative risk, RR=0.59; 95% CI 0.38-0.91), multiplicity of PIN per rat per group by 48.4% (р=0.0081), the incidence of PIN in 2 or 3 lobes of the prostate from 55.9 to 27.6% (р=0.0402), the incidence of PIN in the dorsolateral prostate from 70.6 to 41.4% (р=0.0240), the incidence of PIN in the ventral lobe from 47.1 to 20.7% (р=0.0362). The polyprenol complex exhibited a pronounced anticancer effect against induced prostate tumors. In the group of animals receiving the tested agent, there was a significant decrease in the total incidence of PCa from 64.7 to 34.5% (р=0.0234; RR=0.53; 95% CI 0.30-0.93), as well as the multiplicity of PCa per rat per group and per PIN carrier by 63.4% (р=0.0024) and by 30.6% (р=0.0240) respectively. In the polyprenols group we observed significant decrease in the incidence of prostate cancer in 2 or 3 lobes from 32.4 to 6.9% (р=0.0147) and the incidence of PCa in the dorsolateral prostate from 58.8 to 24.1% (р=0.0101). Oral administration of polyprenols provided a nonsignificant trend towards a decrease in the incidence of metastatic prostate cancer from 32.4 to 20.7% (р=0.3962).

Conclusion. Chronic oral consumption of polyprenols from the needles of Picea abies L. and Pinus sylvestris L. (12.5 mg/kg per day) significantly suppresses the development of PIN and PCa induced by MNM and a mixture of testosterone esters in male Wistar rats. Despite the exploratory nature of the study, our results can serve the rationale for further investigation of polyprenols in prostate cancer chemoprevention trials.

Keywords:prostate cancer, chemoprevention, polyprenols, cancerogenesis, preclinical study

Funding. The research had no financial support.

Conflict of interest. The authors declare that there is no conflict of interest.

For citation: Murazov Ia.G., Nyuganen A.O., Artemyeva A.S. Evaluation of the chemopreventive potential of polyprenols from the needles of Picea abies L. and Pinus sylvestris L. using the model of prostate carcinogenesis in male Wistar rats. Voprosy pitaniia [Problems of Nutrition]. 2021; 90 (3): 104-15. DOI: https://doi.org/10.33029/0042-8833-2021-90-3-104-115 (in Russian)

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CHIEF EDITOR
CHIEF EDITOR
Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

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