Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits bladder cancer cell growth via the mitochondrial apoptosis and JNK pathways.

Erianin, a component extracted from the traditional Chinese herbal medicine Dendrobium, has shown significant anti-tumour activity in various cancers but not in bladder cancer. In this study, we assessed the effects of Erianin on bladder cancer growth and elucidated the related mechanisms. First, Erianin was synthesized with high yields, and markedly suppressed EJ and T24 cell proliferation. It induced G2/M-phase arrest in vitro. Furthermore, Erianin triggered apoptosis via caspase cascades activation and the mitochondrial-mediated apoptotic pathway. Bim up-regulation and Bcl-2 down-regulation as the symbol of apoptosis which were found to play the dominant role in the effects of Erianin. We further showed that JNK pathway activation is necessary for the Erianin-mediated anti-proliferation and apoptotic response. Finally, Erianin exhibited anti-tumour activity and induced apoptosis in tumour tissue in vivo. Collectively, these results suggest that Erianin induced cell cycle G2/M-phase arrest and apoptosis via the JNK signalling pathway in bladder cancer, indicating the potential usefulness of Erianin for the therapy of bladder cancer.

Genipin Enhances the Therapeutic Effects of Oxaliplatin by Upregulating BIM in Colorectal Cancer.

Despite an increase in the survival rate of patients with cancer owing to the use of current chemotherapeutic agents, adverse effects of cancer therapies remain a concern. Combination therapies have been developed to increase efficacy, reduce adverse effects, and overcome drug resistance. Genipin is a natural product derived from Gardenia jasminoides, which has been associated with anti-inflammatory, anti-angiogenic, and anti-proliferative effects; hypertension; and anti-ischemic brain injuries. However, the enhancement of oxaliplatin sensitivity by genipin remains unexplored. Our study showed that a combination of genipin and oxaliplatin exerts synergistic antitumor effects in vitro and in vivo in colorectal cancer cell lines through the reactive oxygen species (ROS)/endoplasmic reticulum (ER) stress/BIM pathway. Importantly, the combination did not affect normal colon cells. BIM knockdown markedly inhibited apoptosis induced by the combination. In addition, genipin induced ROS by inhibiting superoxide dismutase 3 activity. These findings suggest that genipin may be a novel agent for increasing the sensitivity of oxaliplatin against colorectal cancer. The combination of oxaliplatin and genipin hold significant therapeutic potential with minimal adverse effects.

Selenium supplementation modulates apoptotic processes in thyroid follicular cells.

Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate. Furthermore, Se reduces the proportion of cell death and modulates both proapoptotic (p53 and Bim) and antiapoptotic (NF-kB and Bcl2) mRNA levels. In addition, incubation with high doses of Na-Se might prevent the ER-stress apoptosis induced by tunicamycin, as assessed by membrane integrity maintenance, reduction in caspase 3/7 activities, and reduction in Casp-3 and PARP cleavage. Taken together, these results provide molecular evidences indicating the role of Se supplementation on cell death and apoptosis modulation in thyroid follicular cells. These observations may be useful to understand the effects of this micronutrient on the physiopathology of the thyroid gland. © 2016 BioFactors, 43(3):415-423, 2017.

Anticancer activity of Ashwagandha against human head and neck cancer cell lines.

BACKGROUND: The aim of this study was to determine the apoptotic activity of methanol extract of Ashwagandha (MEAG) and in human head and neck squamous cell carcinoma (HNSCC) cells and to investigate the underlying mechanisms. METHODS: We investigated the effects of MEAG on programmed cell death in HNSCC cells using a Live/Dead assay, detection of nuclear morphologic changes, Mitotracker, siRNA knockdown, and RT-PCR. RESULTS: Treatment with MEAG showed dose-dependent growth-inhibitory activity that attribute to caspase-dependent apoptosis. Loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase 9 suggested that MEAG leads to activation of mitochondria-mediated apoptosis. MEAG selectively upregulated the expression of Bim protein at the transcriptional level and induced the translocation of Bim into the mitochondria. Knockdown of Bim by siRNA partially blocked MEAG-mediated apoptosis. MEAG also caused an increase in truncated Bid (t-Bid), cleaved caspase-8, and death receptor 5 (DR5). Interestingly, withaferin A (WA), a bioactive component of MEAG, clearly induced apoptosis accompanied by upregulation of Bim, t-Bid, caspase-8, and DR5 similar to the effects of MEAG. CONCLUSIONS: These suggest that MEAG and WA may be potential natural materials for the treatment of HNSCC.