Anticancer activity of probiotics – experimental and clinical studies

Georgi Alexandrov¹, Kaloyan Georgiev², Marieta Georgieva², Ivan Iliev³, Maria Peneva⁴

Abstract

Introduction: Many scientists have been working on the anticancer effect of probiotics for the past decades. In the middle of the last century I. Bogdanov proved experimentally that Lactobacillus subsp. bulgaricus inhibits the growth and proliferation of tumor cells of Sarcoma 180, implanted in rats. Kitadzava (Japan) ascertained good anticancer effect of fermented milk on rats with implanted tumor cells. A. Hosono (Japan) found out that anticancer effect of fermented milk is due to the lactic acid bacteria and polysaccharides contained in it. Our preliminary studies showed that probiotic Laktera Nature® has an anti-proliferative effect against aggressive colon carcinoma cell line HT-29. The probiotic Laktera Nature® contains original strains of Lactobacillus bulgaricus DWT1 and Streptococcus thermophilus DWT4, isolated from spring water in Bulgaria and 21 natural essential and non-essential lactic amino acids. The aim of this study is to determine the anticancer activity of the different ingredients of probiotic Laktera Nature® and to study the effect of the probiotic formula as a nutritional therapy in patients with colorectal cancer.

Materials and Methods: Four types of cell lines have been used: 3T3, BJ, HT-29 & MDA-MB-231. Cytotoxicity was determined by MTT-dye reduction assay. The direct cytotoxicity of the tested cell lines, measured at the 24th hour and the antiproliferative activity, measured at the 72nd hour have been studied. Four different samples of Laktera Nature® were used: sample 1 (original probiotic formula containing live cells of Lactobacillus bulgaricus DWT1 and Streptococcus thermophilus DWT4 and 21 lactic amino acids), sample 2 (only the probiotic strains without the amino acids), sample 3 (only the 21 lactic amino acids without the probiotic strains) and sample 4 (the original probiotic formula that has passed γ-sterilization 10 Gy, whereby the probiotic strains are killed, leaving only the cell walls). The clinical study is carried out on 13 patients with surgery for colorectal cancer and undergoing chemo- and radiotherapy. Half of the patients take 15 g daily dose Laktera Nature® (sample 1) as a nutritional therapy.

Results and Discussion: The four samples show a negligible direct cytotoxicity of the tested cell lines measured at the 24th hour. Samples 3 and 4 show a slight concentration- and time-dependent cytotoxic effect. It was interesting to observe that sample 2 (only the probiotic strains) did not have the expected inhibitory effect on carcinoma growth (in that case MDA-MB-231), it even increased its growth. Sample 1 (the original probiotic formula Laktera Nature®, containing live probiotic strains and 21 amino acids) demonstrated a significant growth inhibition of cancerous HT-29 and MDA-MB-231 cell lines with IC50 values – 711,69 ± 82,1 and 934,21 ± 43,5 mcg/ml respectively, measured at the 72nd hour. The parallel conducted clinical trial shows that the nutritional therapy with the original probiotic formula Laktera Nature® allows the full courses of treatment with chemo- and radiotherapy to be carried out and reduces the side effects of the chemo- and radiotherapy.

Conclusion: The original probiotic formula Laktera Nature® inhibits growth of cancerous HT-29 and MDA-MB-231 cell lines. The nutritional therapy with Laktera Nature® improves quality of life and increases the survival rate of patients with colorectal cancer.

Keywords: Probiotic, Laktera Nature®, Lactobacillus bulgaricus, amino acids, antitumor effect, anticancer effect, cytotoxicity, nutritional therapy, colorectal cancer.

¹ – Military Medical Academy – Sofia, Bulgaria

² – Department of Preclinical and Clinical Sciences, Sector Pharmacology and Toxicology, Faculty of Pharmacy, Medical University Varna, Bulgaria

³ – Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria

⁴ – Medical Centre “Evrozdrave” Sofia, Bulgaria

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