[May 3, 2023: Staff Writer, The Brighter Side of News]
Lung cancer is the leading cause of death in Japan and across the globe. Among all the cancers, lung cancer has one of the lowest five-year survival rates. (CREDIT: Creative Commons)
Lung cancer stands as the foremost cause of mortality in Japan and around the world. Among all cancer types, it exhibits one of the poorest five-year survival rates. The consumption of tobacco and tobacco-derived products is a significant factor in the development of this disease. However, it has been clinically proven that certain active compounds found in various fruits can reduce the risk of chronic illnesses, including cancer.
"Sarunashi" (Actinidia arguta), an edible fruit grown in the Okayama Prefecture of Japan, has shown promising results in the prevention and reduction of lung cancer. Led by Dr. Sakae Arimoto-Kobayashi, an Associate Professor in the Faculty of Pharmaceutical Sciences at Okayama University, a team of researchers demonstrated that both Sarunashi juice and its constituent isoquercetin (isoQ) are beneficial in this regard, as evidenced by their studies on a mouse model.
A. arguta stands out as an abundant source of polyphenols and vitamin C. Prior to this, scientists showcased the inhibitory impact of Sarunashi juice (sar-j) on mutagenesis, inflammation, and mouse skin tumor development. The components responsible for the anti-mutagenic properties in A. arguta were identified as heat-sensitive and water-soluble phenolic compounds.
Following this, the scientists suggested the polyphenolic compound isoQ as a key component possessing anti-cancer potential.
According to Dr. Arimoto-Kobayashi, “In this study, we sought to investigate the chemo‑preventive effects of A. arguta juice and its constituting component isoQ on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice, and identify the possible mechanisms underlying the anti-tumorigenic effects of A. arguta.”
To achieve this, the researchers initiated tumor growth in mice using NNK, a carcinogenic compound commonly found in tobacco products. Through a series of experiments and controls, they analyzed the impact of sar-j and isoQ on lung tumor development in the mice.
Dr. Arimoto-Kobayashi shares that the findings were promising: Mice treated with NNK injections and oral doses of A. arguta juice exhibited a notably reduced number of tumor nodules in their lungs compared to those only injected with NNK. Additionally, the oral administration of isoQ also contributed to a decrease in the number of lung nodules in the mice.
Actinidia arguta, also known as the hardy kiwi, is a perennial vine that originates from Japan, Korea, Northern China, and the Russian Far East. (CREDIT: Creative Commons)
Following this, the research team made significant progress by identifying the probable mechanism of action. Both NNK and 1-methyl-3-nitro-1-nitrosoguanidine, or "MNNG," are recognized mutagens—substances that provoke DNA mutations. Consequently, the researchers devised a series of experiments to investigate the impact of sar-j and isoQ on NNK- and MNNG-induced mutagenesis, utilizing Salmonella typhimurium TA1535, a bacterial strain frequently employed for detecting DNA mutations.
As anticipated, the mutagenic properties of NNK and MNNG, when assessed with S. typhimurium TA1535, diminished in the presence of sar-j. However, when comparable tests were performed using S. typhimurium YG7108, a strain lacking essential DNA repair enzymes, sar-j failed to reduce the mutagenic impact of NNK and MNNG. Based on this crucial finding, the scientists determined that sar-j appears to exert its antimutagenic influence by hastening DNA repair.
A representative tumor (adenoma/adenocarcinoma) corresponding to the nodule counted macroscopically and the alveolar area around the tumor in the A/J mouse at 30 weeks of age treated with NNK alone (group I). (CREDIT: GenesEnvironment)
Furthermore, through cell-based experiments, the researchers also demonstrated that sar-j hindered the activity of "Akt," a critical protein involved in cancer signaling pathways. It is well-established that Akt, along with a related protein called "PI3k," become overactive in various human cancers.
Co-author Katsuyuki Kiura, a Professor in the Department of Allergy and Respiratory Medicine, Okayama University Hospital, muses, “Sar-j and isoQ reduced NNK-induced lung tumorigenesis. Sar-j targets both the initiation and growth or progression steps during carcinogenesis, specifically via anti-mutagenesis, stimulation of alkyl DNA adduct repair, and suppression of Akt-mediated growth signaling. IsoQ might contribute in part to the biological effects of sar-j via suppression of Akt phosphorylation, but it may not be the main active ingredient.”
NNK-induced pulmonary lesion (group I) in the A/J mouse at 30 weeks of age. Figure 2a, higher magnification of the tumor in Fig. 1a and 1d. Tumor cells with prominent nuclei with mitotic figures (white head) are observed. (CREDIT: GenesEnvironment)
Their findings were published in Genes and Environment.
To sum up, the research demonstrates that the development of lung tumors in mice was inhibited after consuming sar-j orally. While further clinical trials are needed, the components that make up sar-j, such as isoQ, appear to be promising candidates for cancer prevention.
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