The edible fruit Actinidia arguta, commonly called Sarunashi, is grown in the Okayama Prefecture of Japan. Sakae Arimoto-Kobayashi, PhD, an associate professor in the faculty of pharmaceutical sciences at Okayama University, and his team have shown in a mouse model that Sarunashi juice (Sar-j) and its primary component, isoquercetin (isoQ), can both prevent and decrease lung cancer. In research titled “Chemopreventive effects and anti-tumorigenic mechanisms of Actinidia arguta, known as sarunashi in Japan toward 4 (methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in a/J mouse,” the authors published their findings in the journal Genes and Environment.
Sar-j targets both the onset and growth/progression processes in carcinogenesis, particularly, via anti-mutagenesis, stimulating repair of alkyl-DNA adducts, and inhibition of Akt-mediated growth signals, the researchers said in their article.
Lung cancer has one of the worst five-year survival rates of all cancers and is the primary cause of death in both Japan and the rest of the world. It is well known that using tobacco products and smoking tobacco contribute significantly to the onset of lung cancer. According to the authors, molecular epidemiological studies have looked at the association between lung cancer and tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK is thought to be a key contributor to the development of lung cancer in smokers since it successfully develops lung tumors in mice, rats, and hamsters.
The scientists hypothesized that the active components in different fruits might decrease the likelihood of chronic illnesses, including cancer. This is a fact that has been demonstrated in clinical studies. The link between a high fruit diet and a decreased risk of chronic illnesses is supported by epidemiological data. Fruits’ bioactive characteristics have long been the subject of research.
According to the researchers, A. arguta is one of the greatest sources of polyphenols and vitamin C. They had previously shown that Sarunashi juice inhibited mutagenesis, inflammation, and the development of mice skin tumors, and they had also identified the A. arguta constituents that were in charge of the anti-mutagenic actions as being water-soluble and heat-sensitive phenolic compounds. The main polyphenol in A. arguta, isoQ, was then suggested by the researchers as a constituent with anticarcinogenic capabilities.
In their recently published study, Arimoto-Kobayashi stated that they sought to examine the chemopreventive outcomes of A. arguta juice and its constituting element isoQ on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer progression in A/J mice and determine the possible mechanisms underlying the anti-tumorigenic implications of A. arguta.
The researchers looked at how sar-j and isoQ affected the development of lung tumors in mice that had received injections of the cancer-causing substance NNK. The findings were favorable, demonstrating that the proportion of tumor nodules per mouse lung was much fewer in the group that got both NNK injections and oral dosages of A. arguta juice compared to the group that received only NNK injections. Notably, sar-j fully prevented tumor development in 5 out of 9 mice and decreased NNK-induced lung nodules by an average of 25.4%, according to the researchers. IsoQ given orally also decreased the quantity of nodules in mice lungs.
The researchers then looked at the possible sar-j mechanism of action. Known mutagens include NNK and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). The scientists employed Salmonella typhimurium TA1535, a bacterial strain typically used for identifying DNA abnormalities, in a series of studies to investigate the impact of sar-j and isoQ on NNK- and MNNG-mediated mutagenesis. As predicted, the addition of sar-j reduced the mutagenicity of NNK and MNNG as measured using S. typhimurium TA1535. Similar investigations employing S. typhimurium YG7108, a strain deficient in essential DNA repair enzymes, however, revealed that sar-j was unable to lessen the mutagenic effects of NNK and MNNG. This crucial finding led the researchers to the conclusion that sar-j appears to promote its antimutagenic activity via speeding up DNA repair.
Finally, the scientists demonstrated using cell-based tests that sar-j inhibited the activity of Akt, a crucial protein implicated in cancer signaling. It is known that Akt and its companion protein Pi3k are overactive in a number of human cancers.
Sar-j and isoQ lowered NNK-induced lung carcinogenesis, Arimoto-Kobayashi, co-author Katsuyuki Kiura, PhD, a professor in the department of allergy and respiratory medicine, Okayama University Hospital, and collaborators wrote in their research. Sar-j precisely targets the anti-mutagenesis, activation of alkyl DNA adduct repair, and reduction of Akt-mediated growth signaling throughout the beginning and development/progression phases of carcinogenesis. IsoQ may not be the primary active component of sar-j, but it may help in part with the biological effects through reduction of Akt phosphorylation.
The research group suggests that isoQ and other sar-j constituents may make good chemoprevention options.
Takata, J., Miyake, N., Saiki, Y. et al. Chemopreventive effects and anti-tumorigenic mechanisms of Actinidia arguta, known as sarunashi in Japan toward 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)- induced lung tumorigenesis in a/J mouse. Genes and Environ 44, 26 (2022). https://doi.org/10.1186/s41021-022-00255-0
Lung Cancer Growth Suppressed in Mice Using Japanese Fruit (genengnews.com)