19 research outputs found
Intrauterine inoculation of minipigs with Chlamydia trachomatis during diestrus establishes a longer lasting infection compared to vaginal inoculation during estrus
Genital tract lesions in sexually mature GĂśttingen minipigs during the initial stages of experimental vaginal infection with Chlamydia trachomatis serovar D
âThe Good, Pure Old Daysâ: Cyclist's Switching Appraisals of Doping before and after Retirement as Claims Making in the Construction of Doping as a Social Problem
Evaluation of comorbidity in 9388 head and neck cancer patients:A national cohort study from the DAHANCA database
Evaluation of comorbidity in 9388 head and neck cancer patients:A study from the DAHANCA database
The impact of comorbidity on outcome in 12 623 Danish head and neck cancer patients:a population based study from the DAHANCA database
The impact of comorbidity on outcome in 12 623 Danish Head and Neck Cancer Patients: A population based study from the DAHANCA database
Curcumin effectively inhibits oncogenic NF-kB signaling and restrains stemness features in liver cancer
BACKGROUND & AIMS: The cancer stem cells (CSCs) have important therapeutic implications for multi-resistant cancers including hepatocellular carcinoma (HCC). Among the key pathways frequently activated in liver CSCs is NF-kB signaling. METHODS: We evaluated the CSCs-depleting potential of NF-kB inhibition in liver cancer achieved by the IKK inhibitor curcumin, RNAi and specific peptide SN50. The effects on CSCs were assessed by analysis of Side Population (SP), sphere formation and tumorigenicity. Molecular changes were determined by RT-qPCR, global gene expression microarray, EMSA, and Western blotting. RESULTS: HCC cell lines exposed to curcumin exhibited differential responses to curcumin and were classified as sensitive and resistant. In sensitive lines, curcumin-mediated induction of cell death was directly related to the extent of NF-kB inhibition. The treatment also led to a selective CSC-depletion as evidenced by a reduced SP size, decreased sphere formation, down-regulation of CSC markers and suppressed tumorigenicity. Similarly, NF-kB inhibition by SN50 and siRNA against p65 suppressed tumor cell growth. In contrast, curcumin-resistant cells displayed a paradoxical increase in proliferation and expression of CSC markers. Mechanistically, an important component of the CSC-depleting activity of curcumin could be attributed to a NF-kB-mediated HDAC inhibition. Co-administration of the class I/II HDAC inhibitor trichostatine sensitized resistant cells to curcumin. Further, integration of a predictive signature of curcumin sensitivity with human HCC database indicated that HCCs with poor prognosis and progenitor features are most likely to benefit from NF-kB inhibition. CONCLUSIONS: These results demonstrate that blocking NF-kB can specifically target CSC populations and suggest a potential for combined inhibition of NF-kB and HDAC signaling for treatment of liver cancer patients with poor prognosis