Dithiolation indolizine exerts viability suppression effects on A549 cells via triggering intrinsic apoptotic pathways and inducing G2/M phase arrest

Article abstract of DOI:10.1016/j.biopha.2020.110961

Indolizine derivatives have been reported for the treatment of numerous diseases. However, few studies were carried out for non-small cell lung cancer (NSCLC). We synthesized series of indolizine compounds. The results of MTT assay showed compound 8 (C8) markedly inhibited the proliferation of A549 cells, however, C8 (15, 30 μg/mL) had little cytotoxicity in other cell lines (SH-SY5Y, HepG2, and BEAS-2B cells), Hoechst staining and JC-1 staining showed that C8 induced changes in the nucleus morphology, increased the loss in mitochondrial membrane potential in A549 cells. The results of flow cytometry manifested that cell cycle of the cells was arrested in the G2 / M phase by C8, ROS levels and the proportion of apoptosis of cells increased. We performed western blotting analysis to detect the expression levels of apoptosis and cycle-related proteins. These results validated that the apoptosis of cells was triggered by endoplasmic reticulum stress (ERS) and the PI3K/Akt-mediated mitochondrial pathway collaboratively. Besides, the utilization of PI3K/Akt inhibitors and p53 inhibitors further proves the above argument and C8-induced cycle arrest of A549 cells is majorly regulated by p53. C8 induced the accumulation of ROS contents involved in mitochondrial damage. The proliferation of A549 cells was inhibited after treatment with the compound, which induced apoptosis and cycle arrest of cells. It is suggested that C8(dithiolation indolizine) is a potential candidate compound against non-small cell lung cancer.

Full text of DOI:10.1016/j.biopha.2020.110961

2137
JACC March 21, 2017
Volume 69, Issue 11
FIT Clinical Decision Making
SUDDEN UNEXPECTED DEATH IN EPILEPSY AND LONG QT SYNDROME
Moderated Poster Contributions
Spotlight on Special Categories Moderated Poster Theater, Poster Hall, Hall C
Sunday, March 19, 2017, 1:00 p.m.-1:10 p.m.
Session Title: FIT Clinical Decision‐Making: Arrhythmias and Clinical Electrophysiology
Abstract Category: Arrhythmias and Clinical EP
Presentation Number: 1321M-07
Authors: Stephen Gannon, Anthony F. Chu, Rhode Island Hospital/Brown University Alpert Medical School, Providence, RI, USA
Background: Approximately 28% of patients with confirmed long QT syndrome (LQTS) present with a seizure phenotype. Sudden
unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with intractable epilepsy and conveys a mortality
risk 24 times greater than the general population.
Case: 42-year-old female with a past medical history of seizures refractory to antiepileptic drugs was referred to cardiology for evaluation
of palpitations without syncope. The patient had prior coronary angiography which revealed no significant coronary disease. Her baseline
ECG revealed normal sinus rhythm, rare PVCs and a variable QTc interval of 460-508 msec. The patient was treated with a beta-blocker
and an outpatient event monitor was placed. During sleep, the patient had a witnessed grand mal seizure for which she received CPR. She
was wearing the event monitor at the time of her seizure revealing a six-minute episode of polymorphic ventricular tachycardia. Genetic
testing was positive for LQT-1.
Decision‐Making: Identifying patients at risk for SUDEP includes careful assessment for cardiac arrhythmias. The decision for cardiac
monitoring and genetic testing was critical to establishing the diagnosis. SUDEP high risk features include age 20-40 and intractable
epilepsy.
Conclusions: LQTS may present with a seizure phenotype. SUDEP conveys a high mortality and may be due to an inherited cardiac
channelopathy. Clinical awareness and appropriate arrhythmia evaluation are critical to diagnosis.