title: Jaeumganghwa-Tang Induces Apoptosis via the Mitochondrial Pathway and Lactobacillus Fermentation Enhances Its Anti-Cancer Activity in HT1080 Human Fibrosarcoma Cells.
abstract: Jaeumganghwa-tang (JGT, Zi-yin-jiang-huo-tang in Chinese and Jiin-koka-to in Japanese) is an oriental herbal formula that has long been used as a traditional medicine to treat respiratory and kidney diseases. Recent studies revealed that JGT exhibited potent inhibitory effects on allergies, inflammation, pain, convulsions, and prostate hyperplasia. Several constituent herbs in JGT induce apoptotic cancer cell death. However, the anti-cancer activity of JGT has not been examined. In this study, we investigated the anti-cancer effects of JGT using highly tumorigenic HT1080 human fibrosarcoma cells and elucidated the underlying mechanisms. In addition, we examined whether the Lactobacillus fermentation of JGT enhanced its anti-cancer activity using an in vivo xenograft model because fermentation of herbal extracts is thought to strengthen their therapeutic effects. Data revealed that JGT suppressed the growth of cancer cells efficiently by stimulating G1 cell cycle arrest and then inducing apoptotic cell death by causing mitochondrial damage and activating caspases. The phosphorylation of p38 and ERK also played a role in JGT-induced cell death. In vitro experiments demonstrated that JGT fermented with Lactobacillus acidophilus, designated fJGT162, elicited similar patterns of cell death as did non-fermented JGT. Meanwhile, the daily oral administration of 120 mg/kg fJGT162 to HT1080-bearing BALB/c nude mice suppressed tumor growth dramatically (up to 90%) compared with saline treatment, whereas the administration of non-fermented JGT suppressed tumor growth by ~70%. Collectively, these results suggest that JGT and fJGT162 are safe and useful complementary and alternative anti-cancer herbal therapies, and that Lactobacillus fermentation improves the in vivo anti-cancer efficacy of JGT significantly.
authors.affiliation: Korean Medicine (KM)-Based Herbal Drug Development Center, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea.
authors.forename: Aeyung
authors.initials: A
authors.lastname: Kim
authors.affiliation: Korean Medicine (KM)-Based Herbal Drug Development Center, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea.
authors.forename: Minju
authors.initials: M
authors.lastname: Im
authors.affiliation: Korean Medicine (KM)-Based Herbal Drug Development Center, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea.
authors.forename: Youn-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: Korean Medicine (KM)-Based Herbal Drug Development Center, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Korean Medicine (KM)-Based Herbal Drug Development Center, Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D007779:Lactobacillus acidophilus; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D009363:Neoplasm Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases