DNA Damage in Healthy Individuals and Respiratory Patients after Treating Whole Blood In vitro with the Bulk and Nano Forms of NSAIDs.

Mojgan Najafzadeh,Badie K Jacob,Mohammad Isreb,Diana Anderson,Rajendran C Gopalan,Charmaine Normington

doi:10.3389/fmolb.2016.00050

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzyme activity which affects the inflammatory response. Inflammation is associated with increasing cancer incidence. Pre-clinical and clinical studies have shown that NSAID treatment could cause an anti-tumor effect in cancers. In the present study, blood was taken from healthy individuals (n = 17) and patients with respiratory diseases or lung cancer (n = 36). White blood cells (WBC) were treated with either a micro-suspension, i.e., bulk (B) or nano-suspension (N) of aspirin (ASP) or ibuprofen (IBU) up to 500 μg/ml in the comet assay and up to 125 μg/ml in the micronucleus assay. In this study results were compared against untreated lymphocytes and their corresponding treated groups. The results showed, that NSAIDs in their nano form significantly reduced the DNA damage in WBCs from lung cancer patients in bulk and nano compared to untreated lymphocytes. Also, there was a decrease in the level of DNA damage in the comet assay after treating WBCs from healthy individuals, asthma and COPD groups with aspirin N (ASP N) but not with IBU N. In addition, the number of micronuclei decreased after treatment with NSAIDs in their nano form (ASP N and IBU N) in the healthy as well as in the lung cancer group. However, this was not the case for micronucleus frequency in asthma and COPD patients. These data show that lymphocytes from different groups respond differently to treatment with ASP and IBU as measured by comet assay and micronucleus assay, and that the size of the suspended particles of the drugs affects responses.

Highlights

Extensive pre-clinical data and a limited number of clinical investigations have proposed a direct effect of non-steroidal anti-inflammatory drugs (NSAIDs) on tumor biology, with an anti-tumor effect on several of the hallmarks of cancer, including proliferative capacity, evasion of apoptosis and cell cycle regulation, and invasive capability of tumor cells (Park et al, 2014)
DNA damage decreased in lymphocytes from healthy individuals, asthma, chronic obstructive pulmonary disease (COPD) and lung cancer patient groups after treatment with aspirin nanosuspension (ASP N) and ibuprofen nanosuspension (IBU N) compared to their bulk version in the Comet assay (P ≤ 0.01)
When aspirin N (ASP N) was compared to untreated lymphocytes in all groups in the Comet assay, DNA damage significantly decreased in all groups, except the asthma group

Summary

Introduction

Extensive pre-clinical data and a limited number of clinical investigations have proposed a direct effect of non-steroidal anti-inflammatory drugs (NSAIDs) on tumor biology, with an anti-tumor effect on several of the hallmarks of cancer, including proliferative capacity, evasion of apoptosis and cell cycle regulation, and invasive capability of tumor cells (Park et al, 2014). Clinical evidence has suggested a pertinent role in down-regulating the systemic inflammatory response whilst favorably influencing the local inflammatory response within the tumor microenvironment (Hussain et al, 2012). Burn et al (2011) examined the effect of aspirin on cancer risk in carriers of hereditary colorectal cancer in the Colorectal Adenoma/Carcinoma Prevention Programme (CAPP) randomized controlled trial. They concluded that 600 mg per day for a mean of 25 months reduced cancer incidence after 58 months in carriers of hereditary colon cancer (Burn et al, 2011). Together these data provide convincing evidence for the chemopreventive efficacy of NSAIDs in the large bowel (Baron, 2009; Brady et al, 2011; Seufert et al, 2013)

Methods

Results

Conclusion