Caudatin potentiates the anti-tumor effects of TRAIL against human breast cancer by upregulating DR5.

BACKGROUND: The ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to preferentially induce apoptosis in transformed cells while sparing most normal cells is well established. However, the intrinsic and acquired resistance of tumors to TRAIL-induced apoptosis limits its therapeutic applicability. PURPOSE: We investigated the effect of caudatin, a species of C-21 steroidal glycosides isolated from the roots of Cynanchum auriculatum, on TRAIL-induced apoptosis in human breast cancer cells. METHODS: Cell growth inhibition was evaluated by the CCK-8 assay. The cell cycle distribution was assessed by propidium iodide flow cytometry. Apoptosis was determined by TUNEL staining. Protein expression was detected by western blotting analysis. RESULTS: Caudatin enhanced TRAIL-induced apoptosis in human breast cancer cells. This sensitization was achieved by upregulating death receptor 5 (DR5). Knockdown of DR5 abolished the enhancing effect of caudatin on TRAIL responses. The caudatin-induced upregulation of DR5 was accompanied by increased expression of CHOP and phosphorylation of p38 MAPK and JNK. CHOP knockdown blocked caudatin-upregulated DR5 expression. Moreover, cotreatment of breast cancer cells with p38 MAPK and JNK inhibitors significantly counteracted the caudatin-induced expression of DR5. CONCLUSION: Our results showed that caudatin sensitized breast cancer cells to TRAIL-induced apoptosis through activation of CHOP, p38 MAPK and JNK-mediated upregulation of DR5 expression. The combination of TRAIL and caudatin may be a promising therapeutic approach for the treatment of breast cancer.

Effect of integrated control intervention on soil-transmitted helminth infections in Jiangxi province in southeast China.

Soil transmitted helminths (STHs) burden was enormous in China several decades ago, however, rigorous control efforts have been successful with appreciable reduction in diseases burden. Here, we assessed provincial-level data derived from cross sectional surveys, executed in 1989, 2002 and 2014, on the prevalence of STHs among populations in Jiangxi province, China. This study, also, reported STHs integrated control intervention aimed at reducing STHs transmission and worm burden among population at county-level. The intervention strategies included mass drug administration (MDA), health education, improved water supply for drinking, improved sanitary facilities and environmental modification in Guixi municipality. The overall infection rate of STHs in Jiangxi province decreased from 77.7% (1989) to 6.3% (2014), while Ascaris lumbricoides, hookworm and Trichuris trichiura decreased from 71.1%, 17.6% and 17.0% (1989) to 0.9%, 4.7% and 1.0% (2014), respectively. STHs infection rates in female population were higher than male in the three surveys. Reduction in STHs prevalence was observed in all age groups, but the decline was less in higher age group. STHs prevalence in Guixi intervention region indicated remarkable reduction from 31.8% (2006) to 6.1% (2009) (χ2＝255.22, P＜0.01). A. lumbricoides, hookworm and T. trichiura infection rates decreased from 10.4%, 17.0% and 7.1% (2006) to 0.1%, 4.1% and 2.2%, respectively (2009) (X2A.l = 110.23, P<0.01; X2hk = 103.57, P < 0.01; X2T.t = 32.0, P < 0.01). A. lumbricoides infection rate declined the most of all STHs. Following control efforts with integrated control intervention strategies, STHs prevalence in Jiangxi province experienced remarkable trend in decline between 1989 and 2014. Consolidating control efforts with sustained integrated control strategies is, therefore, important to achieving STHs elimination in China.