ABSTRACT
The tumor suppressor p53 has a diverse mutational profile in human malignancies, which is known to influence the potency of various chemotherapeutics, such as platins and anti-metabolites. However, the impact of the mutations in the TP53 gene (coding for p53) on the anti-cancer efficacy of gold complexes remains incompletely understood. We therefore investigated the anti-tumor properties of a gold(I) N-heterocyclic carbene (NHC) complex-termed MC3-in human colorectal cancer (CRC) cell lines encompassing three different p53 variations: HCT116 wild-type (WT), HCT116 p53-/-, and HT-29 (mutant; R273H). MC3 treatment induced intracellular reactive oxygen species (ROS) levels, and p21 expression, leading to cell cycle arrest in all cell lines, regardless of their p53 status. The pro-apoptotic response, however, was found to occur in a p53-dependent manner, with WT p53 harboring cells showing the highest responsiveness. Additionally, p73, which was speculated to substitute p53 in p53-deficient cells, was found to be markedly reduced with MC3 treatment in all the cell lines and knocking down its levels did not impact MC3's anti-tumor effects in HCT116 p53-/- cells. Collectively, our results suggest that this small molecule has anti-cancer properties in the context of deficient or mutant p53 and may therefore have chemotherapeutic potential for clinical application.
ABSTRACT
Cantonese has one of the most complex tone systems. Few studies have thoroughly examined or compared the acoustic properties of the full set of Cantonese tones, particularly the entering tones, compromising deeper understanding of Cantonese tone difficulties in various clinical populations. This study (1) describes a theory-driven method for acoustic analysis of tones that successfully normalized the intrinsic pitch of male and female speakers, (2) provides detailed acoustic data on distinctly enunciated Cantonese tones, (3) examines the acoustic similarities and differences between the entering and non-entering tones, and (4) compares the acoustic properties of three easily confused tone pairs. Seventeen male and female native speakers produced 1802 Cantonese tones that were correctly identified by five judges in filtered stimuli. Counter to the established notion that the entering tones are shorter versions of the three level tones, the results revealed that the entering tones have falling contours, suggesting that the entering and non-entering tones should be examined separately in research and clinical settings. The detailed description of the acoustic properties of the nine tones and the acoustic contrasts of the entering and non-entering tones and the three easily confused tone pairs provides references for future Cantonese tone studies with different populations.
