Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling. | LitMetric
Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ/BA), Salvador 40296-710, Bahia, Brazil.
Published: December 2022
AI Article Synopsis
Article Abstract
Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro.
Non-small cell lung cancer (NSCLC) is the most common and prevalent subtype of lung cancer and continues to be one of the leading causes of cancer-related deaths worldwide. Despite various treatment options, a majority of NSCLC patients continue to experience disease progression and associated side effects, which are largely attributed to drug resistance, indicating the need for alternative strategies to combat this deadly disease. Among various applicable alternative approaches, repurposed drugs such as arsenic compounds have been shown to exert anticarcinogenic properties against NSCLC and possess the ability to overcome drug resistance mechanisms.
Oral squamous cell carcinoma (OSCC) is a common head and neck malignant tumour with high incidence and poor prognosis. Arsenic trioxide (ATO) has therapeutic effects on solid tumours. Microwave ablation (MWA) has unique advantages in the treatment of solid tumours.
Background: The treatment of all-trans retinoic acid (ATRA) and arsenical agent has revolutionarily improved the prognosis of acute promyelocytic leukemia (APL) both in adults and children. Nevertheless, coagulation disorder and differentiation syndrome (DS) are the main causes of early death in APL patients. Early chemotherapy to reduce leukocytes during induction is an important measure to reduce complications and mortality.
This study focused on the interplay between NADPH oxidase 2 (NOX 2) activation and mitochondrial superoxide (mitoO) formation induced by clinically relevant concentrations of arsenic trioxide (ATO; AsO) in acute promyelocytic leukemia (APL) cells. Carefully controlled inhibitor studies and small interfering RNA mediated downregulation of p47 (a component of the NOX 2 complex) expression demonstrated that, in an APL cell line, ATO promotes upstream NOX 2 activation critically connected with the formation of mitoO and with the ensuing mitochondrial permeability transition (MPT)-dependent apoptosis. Instead, acute myeloid leukemia (AML) cell lines respond to ATO with low NOX 2 activation, resulting in a state that is non-permissive for mitoO formation.
The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.
