Abstract 116P
Background
Cancer-related fatigue (CRF) is different from the fatigue of daily life in that it is not predictable by tumor type, treatment, or stage of illness. It may be caused by the cancer itself or treatments such as chemotherapy, radiotherapy, and combination therapies. Recent reports suggest that mitochondria in CLL tumor cells have higher levels of mitochondrial respiration (OXPHOS), reactive oxygen species (ROS) formation, metabolic reprogramming, resistance to apoptosis and uncontrolled proliferation that can lead to chemotherapy resistance. Therefore, our study aims to identify the N-Acetyl Cysteine (NAC) to improve the mitochondrial biogenesis in Cybrid model of CLL for improving CRF after chemotherapy.
Methods
Cell metabolism (MTT assay), cell viability (Trypan blue assay), mitochondrial membrane potential (JC-1 assay), ROS (H2DCFDA assay) and RNA (qRT-PCR) was used to evaluate the levels of mitochondrial damage/dysfunction in the CLL cybrids compared to age-matched control cybrids. CLL and Control cybrids treated with NAC was analyzed for their anti-oxidation, anti-apoptosis, anti-inflammation and anti-tumor immunity effects in CLL cybrids. Finally, cybrids were treated with chemotherapy drugs that are used currently for CLL and explored for the protective effects of nutraceuticals on these chemo-treated cells using the mitochondrial based assays.
Results
Blood from CLL and age-matched control subjects were collected and platelets isolated. Non-cancerous Rho0 cells (lacking mtDNA) fused with the platelets to create cybrids that have identical nuclei but mitochondria from different individuals. CLL cybrids showed reduced cell viability, increased ROS, altered bioenergetic profile (more glycolysis), and upregulation of genes related to the inflammatory, oxidative stress and cytokine pathways compared to the age-matched normal cybrids. NAC improved the mitochondrial function and decreased the levels of oxidative stress and genes associated with mitochondrial biogenesis.
Conclusions
This study showed that NAC might reverse the mitochondrial damage, rescue the non-cancerous cells and reduce the CRF often seen in CLL patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Discovery Eye Foundation.
Disclosure
All authors have declared no conflicts of interest.