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.

Effects of Jaeumkanghwa-tang on tamoxifen responsiveness in preclinical ER+ breast cancer model

“…It also is used to treat gynecological health problems (Sekiya et al 2003) or allergic inflammatory reactions (Kim et al 2004). In studies performed in vitro and in vivo in immunocompromised mice, JEKHT inhibited the growth of several cancer cell lines (Kim et al 2015). In immunocompetent rats, JEKHT inhibited the development of benign prostatic hyperplasia (Shin et al 2012).…”

Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice

“…Our previous study showed that SJ fermented by Lactobacillus (FSJ) was associated with increased anti-inflammatory activities on lipopolysaccharides (LPS)-stimulated RAW 264.7 cells compared with SJ 14 . Interestingly, several studies have indicated that fermentation of natural herbs with Lactobacillus strengthen active components, increase physiological potency, and improve absorption efficiency 15 16 . Therefore, in this study, we investigated the potential anti-amnesic effects of SJ and FSJ on hippocampal neurogenesis and cognitive functioning in the scopolamine (SCO)-induced amnesia mouse model.…”

Structure based discovery of clomifene as a potent inhibitor of cancer-associated mutant IDH1

“…Consequently, D-2HG may cause global methylation of histones. After treated with clomifene for 48 hours, histone proteins were extracted and methylation level of H3K9me3 was measured by western blot analysis [ 17 ]. As shown in Figure 2c , clomifene could markedly decrease the level of histone methylation in HT1080 cells with a dose-dependent manner.…”