Several reports have described the anti-cancer activity of arctigenin, a lignan extracted from Arctium lappa L. Here, we investigated the effect of arctigenin (ATG) on doxorubicin (DOX)-induced cell death using MDA-MB-231 human breast cancer cells. The results showed that DOX-induced cell death was enhanced by ATG/DOX co-treatment in a concentration-dependent manner and that this was associated with increased DOX uptake and the suppression of multidrug resistance-associated protein 1 (MRP1) gene expression in MDA-MB-231 cells. ATG enhanced DOX-induced DNA damage and decreased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the expressions of RAD51 and survivin. Cell death caused by ATG/DOX co-treatment was mediated by the nuclear translocation of apoptosis inducing factor (AIF), reductions in cellular and mitochondrial Bcl-2 and Bcl-xL, and increases in mitochondrial BAX levels. However, caspase-3 and -7 did not participate in DOX/ATG-induced cell death. We also found that DOX/ATG-induced cell death was linked with activation of the p38 signaling pathway and suppressions of the phosphorylations and expressions of Akt and c-Jun N-terminal kinase. Taken together, these results show that ATG enhances the cytotoxic activity of DOX in MDA-MB-231 human breast cancer cells by inducing prolonged p21 expression and p38-mediated AIF-dependent cell death. In conclusion, our findings suggest that ATG might alleviate the side effects and improve the therapeutic efficacy of DOX.
Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35 μM. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.
Although colored-leaf tea germplasms can broaden product diversity and functional potential, such resources have been rarely reported in Korea. Herein, we comprehensively characterized Ku2, a newly discovered purple-green line of Camellia sinensis, and benchmarked it against the conventional green-leaf ‘Sangmok’. Five-year-old plants grown under identical open-field conditions were evaluated for growth characteristics, leaf pigmentation, biochemical composition, and antioxidant capacity. Ku2 exhibited a more vigorous growth habit with denser branching and produced leaves that were 11% longer and 17% wider than those of ‘Sangmok’, but chlorophyll concentrations were 29–33% lower. Young shoots of Ku2 in the first flush accumulated markedly higher levels of total polyphenols (+38%), anthocyanins (+78%), and total catechins (+35%), including a 70% increase in epigallocatechin-3-gallate. But amino acid and theanine contents were reduced to 30% and 25% of those in ‘Sangmok’, respectively. Consistent with its polyphenol enrichment, Ku2 extracts displayed superior radical-scavenging activity, with lower DPPH and ABTS IC50 values (7.6 ± 0.5 and 11.6 ± 0.2 µg·mL−1) than ‘Sangmok’ (10.1 ± 0.4 and 15.1 ± 0.1 µg·mL−1), approaching ascorbic acid and Trolox standards. These findings highlight Ku2 as a valuable germplasm for developing premium Korean teas and for breeding colored-leaf cultivars enriched with health-promoting metabolites.
Tea plant [Camellia sinensis (L.) O. Kuntze] is an economically important evergreen crop cultivated worldwide. While most tea plants have green leaves, albino cultivars with yellow or white young leaves have attracted growing interest due to their elevated levels of L-theanine, a key compound that enhances the umami flavor and overall quality of green tea. In this study, we characterized the morphological and biochemical traits of a novel albino tea cultivar, ‘Geumda’, developed in Korea. ‘Geumda’ exhibited yellow young shoots during the first flush and smaller leaves compared to the green-leaf standard cultivar, ‘Sangmok’. Although the catechin content of ‘Geumda’ was lower than that of ‘Sangmok’, it exhibited significantly higher levels of total amino acids, L-theanine, and arginine by 2.1-, 2.0-, and 9.8-fold, respectively. Transmission electron microscopy and gene expression analysis revealed that the elevated amino acid content in ‘Geumda’ was associated with impaired chloroplast development, leading to reduced chlorophyll content and diminished photosynthetic capacity. These findings suggest that ‘Geumda’, with its high concentrations of theanine and arginine and its impaired chloroplast development, represents a valuable genetic resource for the production of functional green teas enriched in umami flavor and beneficial health properties.