Lycorine promotes IDH1 acetylation to induce mitochondrial dynamics imbalance in colorectal cancer cells.

Isocitrate dehydrogenase (IDH) 1 and 2, as essential enzymes in energy metabolism, contribute to the survival and drug resistance of a variety of solid tumors, especially for colorectal cancer (CRC). However, the underlying molecular mechanism still remains unclear. In this study, IDH1 was identified as a crucial cellular target of a natural-derived anti-CRC small molecule lycorine, using the unbiased thermal proteome profiling (TPP) strategy. We found that lycorine directly targeted a unique C-terminal domain of IDH1, and disrupted IDH1 interaction with deacetylase sirtuin 1 (SIRT1), thereby significantly promoting IDH1 acetylation modification. Then, lycorine noticeably triggered oxidative stress in CRC cells to cause mitochondrial membranes injury, and subsequently facilitated mitochondrial fission. Specific knockdown of IDH1 or SIRT1 markedly aggrieved lycorine-mediated oxidative stress and mitochondrial fragmentation in CRC cells. Furthermore, the combination of lycorine and sirtuins blocker nicotinamide (NAM) exhibited a synergic therapeutic effect in CRC cells. Collectively, our results reveal that IDH1 may serve as a promising therapeutic target for CRC via pharmacologically driving oxidative stress-dependent mitochondrial dynamics imbalance.

A novel dithiourea-appended naphthalimide "on-off" fluorescent probe for detecting Hg2+ and Ag+ and its application in cell imaging.

An effective dithiourea-appended 1,8-naphthalimide fluorescent probe was designed and synthesized. This probe could recognize Hg2+ and Ag+ sensitively and selectively in neutral and alkaline conditions. Moreover, the probe detected Hg2+ alone at pH between 2 and 6. The sensing ability of the probe was explored by UV-vis, fluorescence, FTIR and 1H NMR spectroscopy. The probe was quenched by Hg2+ and Ag+ with 1:1 binding ratios in MeCN/H2O (4/1, v/v) mixed solution with binding constants of 3.76 × 104 L mol-1 and 2.47 × 104 L mol-1, respectively. The linear concentration ranges for Hg2+ and Ag+ were 0-17 µmol L-1 and 0-24 µmol L-1 with detection limits of 0.83 µmol L-1 and 1.20 µmol L-1, respectively, which allowed for the quantitative determination of Hg2+ and Ag+. The new probe, 3a, was successfully applied to the fluorescence imaging of Hg2+ and Ag+ in HepG2 cells, demonstrating its potential application in biological science. Moreover, 3a was used to measure Hg2+ and Ag+ in tap water, drinking water and ultrapure water samples. The recoveries of Hg2+ and Ag+ in water samples were 96-99% and 98-103%, respectively. Therefore, the proposed method showed promising perspectives for its application, aimed at detecting Hg2+ and Ag+ in fluorescence imaging and real water samples.

MicroRNA-222 expression and its prognostic potential in non-small cell lung cancer.

Overexpression of miR-222 has been found in several types of cancers; however, the expression of miR-222 in non-small cell lung cancer (NSCLC) and its prognostic values are unclear. This study aimed to investigate whether the miR-222 expression level is related to clinicopathological factors and prognosis of NSCLC. Through a prospective study, 100 pairs of NSCLC tissues and adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between miR-222 expression and clinicopathological features was analyzed, and the significance of miR-222 as a prognostic factor and its relationship with survival were determined. Results showed that the expression levels of miR-222 were significantly elevated in the NSCLC tissue compared with that in adjacent normal tissue. In addition, Cox's proportional hazards model analysis confirmed that miR-222 high expression level was an independent predictor of poor prognosis. In conclusion, miR-222 overexpression is involved in the poor prognosis of NSCLC and can be used as a biomarker for selection of cases requiring especial attention.