In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives.

Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.

Rhodium(III)-Picolinamide Complexes Act as Anticancer and Antimetastasis Agents via Inducing Apoptosis and Autophagy.

As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin ß1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.

Reduction of psychological cravings and anxiety in women compulsorily isolated for detoxification using autonomous sensory meridian response (ASMR).

OBJECTIVE: To explore the effects of the autonomous sensory meridian response (ASMR) on the psychological cravings and anxiety of women compulsorily isolated for detoxification. METHOD: Around 122 women were recruited in a female drug detoxification center. Except for the 12-week training of ASMR, the experimental conditions of the experimental group (n = 60) were the same as those of the control group (n = 62). The addiction Stroop task was used to assess the level of psychological cravings and the State-Trait Anxiety Inventory was used to assess the level of anxiety. RESULTS: After the training, the decrease in state anxiety of the experimental group was larger than that of the control group, and the reaction time of the experimental group in the Stroop was also significantly lower than before the training. CONCLUSIONS: ASMR could thus reduce to a certain extent the state anxiety and attentional bias for drug-related clues under signaling psychological cravings among women compulsorily isolated for detoxification. HIGHLIGHTS: Intervention effects on psychological cravings and anxiety of women isolated for detoxification Basis for role of ASMR in regulating psychological cravings and anxiety in forced abstainers ASMR intervention reduced forced abstainers' attentional bias to drug-related clues.

Terpyridine copper(II) complexes as potential anticancer agents by inhibiting cell proliferation, blocking the cell cycle and inducing apoptosis in BEL-7402 cells.

Four mononuclear terpyridine complexes [Cu(H-La)Cl2]·CH3OH (1), [Cu(H-La)Cl]ClO4 (2), [Cu(H-Lb)Cl2]·CH3OH (3), and [Cu(H-Lb)(CH3OH)(DMSO)](ClO4)2 (4) were prepared and fully characterized. Complexes 1-4 exhibited higher cytotoxic activity against several tested cancer cell lines especially BEL-7402 cells compared to cisplatin, and they showed low toxicity towards normal human liver cells. ICP-MS detection indicated that the copper complexes were accumulated in mitochondria. Mechanistic studies demonstrated that the copper complexes induced G0/G1 arrest and altered the expression of the related proteins of the cell cycle. All copper complexes reduced the mitochondrial membrane potential while increasing the intracellular ROS levels and the release of Ca2+. They also up-regulated Bax and down-regulated Bcl-2 expression levels, caused cytochrome c release and the activation of the caspase cascade, and induced mitochondrion-mediated apoptosis. Animal studies demonstrated that complex 1 suppressed tumor growth in a mouse xenograft model bearing BEL-7402 tumor cells.