Anticancer activity of 8-hydroxyquinoline-triphenylphosphine rhodium(III) complexes targeting mitophagy pathways.

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1-H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a-YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 µM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a-YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.

Late-onset Leigh syndrome without delayed development in China: A case report.

BACKGROUND: Leigh syndrome (LS) is one of the most common mitochondrial diseases in infants and children. LS often manifests as early-onset with delayed phenotypic development. However, late-onset LS with normal development and white matter lesions in the brain is rarely reported, thereby highlighting the phenotypic variability of LS expression. CASE SUMMARY: We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay. The patient was admitted to the hospital with symptoms of ptosis and somnolence, and died within 2 mo. Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient. Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem. The patient was diagnosed with LS. The patient was treated with vitamin C, vitamin D, and adenosine-triphosphate. The patient died within 2 mo of hospital admission. CONCLUSION: LS can present in both infants and older children with different phenotypes.

Role of mitochondrial function in the protective effects of ischaemic postconditioning on ischaemia/reperfusion cerebral damage.

OBJECTIVE: To investigate the effects of ischaemic postconditioning on brain injury and mitochondria in focal ischaemia and reperfusion, in rats. METHODS: Adult male Wistar rats (n = 15 per group) underwent sham surgery, ischaemia (2-h middle cerebral artery occlusion), or ischaemia followed by ischaemic postconditioning (three cycles of 30 s reperfusion/30 s reocclusion). Brain infarction size, neurological function, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential and mitochondrial swelling were evaluated 24 h postsurgery. RESULTS: Infarct size was significantly smaller, and neurological function was significantly better, in the ischaemic postconditioning group than in the ischaemia group. Ischaemia resulted in significant increases in mitochondrial ROS production and swelling, and a reduction in mitochondrial membrane potential, all of which were significantly reversed by postconditioning. CONCLUSIONS: The protective role of ischaemic postconditioning in focal ischaemia/reperfusion may be due to decreased mitochondrial ROS production, reduced mitochondrial membrane potential and suppressed mitochondria swelling. Mitochondria are potential targets for new therapies to prevent brain damage caused by ischaemia and reperfusion.

[Experimental study on antitumor effects of Shen Qi Jin Kang (SQJK)].

BACKGROUND & OBJECTIVE: SHEN QI JIN KANG (SQJK) capsule is a complex preparation, consisting of effective components extracted from radix astragali, ginseng, curcuma, etc. It has been demonstrated to be able to decrease tumor volume, increase life quality and prolong survival time in clinic application. The study was to investigate the antitumor effects of SQJK capsule in vivo and in vitro, and further explore the possible mechanisms. METHODS: The proliferation of cancer cells treated with SQJK was measured by MTT assay in twelve cell lines; cell apoptosis was observed under an electric microscopic and detected by flow cytometry in MCF-7 and MA891 cells; altered telomerase activity in A549 cells was examined by a telomerase activity detection kit. Furthermore, the inhibitory effect of SQJK on tumors was also surveyed in vivo by using mice and nude mice models bearing transplanted tumors. RESULTS: Inhibitory concentration 50% (IC(50)) of SQJK on A549, U251, MCF-7, Ketr-3, EJ, and A2780 cells was 30.954 microg/ml, 31.746 microg/ml, 37.220 microg/ml, 40.366 microg/ml, 41.398 microg/ml, and 45.083 microg/ml, respectively. Typical sub-G1 peaks, indicating the occurrence of apoptosis, were revealed in MA891and MCF-7 cells treated with SQJK. Morphological changes including cell shrinkage and condensation of chromosomes were observed. The telomerase activity of A549 was inhibited after 48 h of SQJK treatment. SQJK 1.8 g/kg inhibited the weights of transplanted tumors (MA891, H22, S180 in mice and PC-3 (M), MCF-7 and Ketr-3 in nude mice) by 50.84%, 48.91%, 40.88%, 62.50%, 47.83% and 30.06%, while SQJK 3.6 g/kg inhibited the weights by 56.49%, 59.62%, 55.70%, 70.76%, 58.66% and 50.18%, respectively. CONCLUSION: SQJK has demonstrated antitumor bioactivity both in vitro and in vivo, which may be related to its effects of inducing apoptosis and decreasing telomerase activity.