JOURNAL OF CANCER PREVENTION http://dx.doi.org/10.15430/JCP.2014.19.4.253 Vol. 19, No. 4, December, 2014 pISSN 2288-3649ㆍeISSN 2288-3657 Cancer Preventive Potential of Kimchi Lactic Acid Review Bacteria (Weissella cibaria, Lactobacillus plantarum) Shin-Hye Kwak1, Young-Mi Cho1, Geon-Min Noh2, Ae-Son Om1 1Laboratory of Food Safety and Toxicology, Department of Food Science and Nutrition, College of Human Ecology, Hanyang University, Seoul, Korea, 2Functional Food and Nutrition Division, Department of Agrofood Resources, National Academy of Agricultural Science, Wanju, Korea The number of death due to cancer has been increasing in Korea. Chemotherapy is known to cause side effects because it damages not only cancerous cells but healthy cells. Recently, attention has focused on food-derived chemopreventive and anti-tumor agents or formulations with fewer side effects. Kimchi, most popular and widely consumed in Korea, contains high levels of lactic acid bacteria and has been shown to possess chemopreventive effects. This review focuses on Weissella cibaria and Lactobacillus plantarum, the representatives of kimchi lactic acid bacteria, in terms of their abilities to prevent cancer. Further studies are needed to understand the mechanisms by which lactic acid bacteria in kimchi prevent carcinogenic processes and improve immune functions. (J Cancer Prev 2014;19:253-258) Key Words: Kimchi, Weissella cibaria, Lactobacillus plantarum, Anticancer, Lactic acid bacteria INTRODUCTION selectively destroy specific cancer cells. However, because of problems, such as tolerance manifestation, partly critical toxicity, According to the Korean national statistical office, the main decrease in sensitivity, and restriction in subjects, new drugs take cause of death in Korea was cancer in 2012. The total number of only a small portion of the cancer treatment realm.3 deaths due to cancer in 2012 was 267,221, which was increased by Chemoprevention is defined as the use of nontoxic or relatively 9,825 (3.8%) compared to 2011.1 This was the all-time high since safe chemical substances, such as vitamins, plant extracts, and 1983. Currently, the treatment of cancer patients in the medical pharmaceuticals to prevent cancer. It is effective in decreasing field consists mainly of surgery, radiation therapy, and chemo- cancer risk and is helpful in early stages of cancer.4 Hence, regular therapy. Seventy to eighty percent of cancer patients in chemo- consumption of anticancer foods that display no or little toxicity therapy experienced side effects such as anemia, the decreased to the body and boost efficacy of anti-tumor drugs or stop the number of white blood cells and/or platelets, oral mucositis, development of tolerance would be beneficial in preventing vomiting, diarrhea, hair loss, and disabled generative functions as cancer. Thus, consumption of plant-derived natural foods to chemotherapy also affects the rapidly proliferating normal cells.2 prevent cancer with few side effects and toxicity is crucial.5 Most side effects are temporary and patients recover fully; but, Recently, there has been a growing interest in probiotics due to some side effects may take months or years to completely the discovery of multidrug-resistant organisms that are tolerant disappear. To decrease side effects from non-specific cytotoxicity, to antibiotics. The word ‘probiotics’ is derived from a Greek word new drugs, such as targeted agents, are being developed to meaning ‘for life’ and holds the opposite meaning from antibio- Received November 8, 2014, Revised December 8, 2014, Accepted December 8, 2014 Correspondence to: Ae-Son Om Laboratory of Food Safety and Toxicology, Department of Food Science and Nutrition, College of Human Ecology, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Korea Tel: +82-2-2220-1203, Fax: +82-2-2220-1856, E-mail: [email protected], ORCID: Ae-Son Om, http://orcid.org/0000-0002-9452-9647 Copyright © 2014 Korean Society of Cancer Prevention cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www.jcpjournal.org 254 Journal of Cancer Prevention Vol. 19, No. 4, 2014 tics which means ‘against life’. Probiotics consist of microorga- induction of apoptosis via the caspase-3 signaling pathway and nisms and substances, which modify the intestinal microflora, cell-cycle arrest.20,21 One possible mechanism of cancer preventive and when used as dietary supplement they have positive effects effects of garlic in stomach cancer development involves its on health such as fortification of host immune function, antimicrobial activities against Helicobacter pylori, a major risk suppression of diarrhea, and inhibition of carcinogenesis.6 factor of stomach cancer.22 Hot red chili pepper powder, one of the Kimchi, a Korean traditional food, is fermented by probiotic main ingredient of kimchi, contains capsaicin (trans-8-methyl-N- lactic acid bacteria.7 Kimchi lactic acid bacteria are known to vanillyl-6-nonenamide). Although the role of capsaicin in suppress the activity of carcinogen-activating enzymes, such as carcinogenic processes has been controversial, there is accumu- azoreductase, nitroreductase, 7-α-dehydrogenase, β-glucosidase, lated evidence that capsaicin is capable to induce apoptosis of and β-glucuronidase and inactivate or neutralize the cancer- cancer cells by generating excess reactive oxygen species.23 causing agents and pathogenic microbes.8 In addition, the intake Thoennissen et al.24 demonstrated that capsaicin caused of lactic acid bacteria as part of kimchi improves bowel move- cell-cycle arrest and apoptosis in breast cancer cells by modulating ment, strengthens immunity, ameliorates hepatocirrhosis, and the EGFR/HER-2 pathway and inhibited the development of decreases serum cholesterol levels.9,10 Among lactic acid bacteria pre-neoplastic breast lesions by up to 80% without toxicity. identified during the fermentation of kimchi, Weissella, Lactoba- In addition to each ingredient of kimchi, kimchi extract was cillus, Leuconostoc and Pediococcus species are known to play an used to investigate cancer preventive/anticarcinogenic activity of important role in kimchi fermentation.11-13 kimchi. Extract of kimchi fermented for 3 weeks inhibited the This commentary deals with anticarcinogenic effects of kimchi proliferation of human cancer cell lines (gastric adenocarcinoma and lactic acid bacteria, Weissella cibaria and Lactobacillus and acute promyelocytic leukemia). Leukemia cells treated with plantarum separated from kimchi, which are known to be kimchi extract showed increased apoptosis and decreased predominant in kimchi. mitochondrial transmembrane potential.25 The juice of 3-week fermented kimchi suppressed the growth of K-562 human ANTICANCER EFFECTS OF KIMCHI leukemia cells and MG-63 human osteosarcoma cells but no toxicity of kimchi juice was found in normal cells.26 Kimchi, a fermented cabbage indispensable to Korean cuisine, Sarcoma180 cells transplanted mice were treated with was once considered to be a risk factor for stomach cancer. methanol extract of 3-week fermented kimchi. Animals provided However, unless one consumes kimchi that contains excess salt, kimchi extract showed in smaller tumor weight and decreased kimchi, in general, is a healthy food recognized for its antioxi- malondialdehyde formation compared to those of the control dant, antiobese, cancer preventive, and other health beneficial group.27 effects.7 Cancer preventive/anticarcinogenic activity of kimchi is associated with the type of ingredients and products formed PROBIOTIC LACTIC ACID BACTERIA IN during fermentation.14 KIMCHI The kimchi’s main ingredient, Chinese cabbage, has been considered to be effective in preventing stomach cancer according Although there has been no general acceptance on how to define to epidemiologic studies and is known to inhibit colorectal probiotic microorganisms, Lactobacillus species, Bifidobacterium carcinogenesis due to its abundance in dietary fiber.15 Garlic, in sp, Saccharomyces boulardii, and some other microbes have been particular, has been acknowledged for its anticancer effect due to thought and used as probiotic strains.28 These probiotic micro- high contents of organosulfur compounds (11 to 35 mg/g). organisms have been used as food supplement in order to achieve Thirty-three types of organosulfur compounds have been health benefit effects of them. identified in garlic.16 Organosulfur compounds in garlic have There have been many studies reported on the functionality of been shown to facilitate the detoxification of carcinogens by lactic acid bacteria in the fermentation process of kimchi and glutathione-S-transferase, modulate the activity of metabolizing their importance in the health beneficial effects of kimchi, enzymes such as cytochrome P450s, and inhibit the formation of including prevention of cancer.29 According to pyrosequencing DNA adducts in several target tissues.17-19 Antiproliferative activity analysis of commercial kimchi samples to identify kimchi lactic of organosulfur compounds has been demonstrated in tumor cell acid bacteria, the genus Weissella was predominant at 44.4%. W. lines including colon, prostate, and breast, which is mediated by koreensis was 27.2% and W. cibaria was 8.7%.7 Shin-Hye Kwak, et al: Cancer Preventive