Abstract

Leptospermum flavescens Sm. (Myrtaceae), locally known as ‘Senna makki’ is a smallish tree that is widespread and recorded to naturally occur in the montane regions above 900 m a.s.l from Burma to Australia. Although the species is recorded to be used traditionally to treat various ailments, there is limited data on biological and chemical investigations of L. flavescens. The aim of the present study was to investigate and understand the ability of L. flavescens in inducing cell death in lung cancer cells. The cytotoxic potentials of the extraction yields (methanol, hexane, ethyl acetate and water extracts as wells as a semi pure fraction, LF1) were evaluated against two human non-small cell lung carcinoma cell lines (A549 and NCI-H1299) using the MTT assay. LF1 showed the greatest cytotoxic effect against both cell lines with IC50 values of 7.12 ± 0.07 and 9.62 ± 0.50 μg/ml respectively. LF1 treated cells showed a sub-G1 region in the cell cycle analysis and also caused the presence of apoptotic morphologies in cells stained with acridine orange and ethidium bromide. Treatment with LF1 manifested an apoptotic population in cells that were evaluated using the Annexin V/ propidium iodide assay. Increasing dosage of LF1 caused a rise in the presence of activated caspase-3 enzymes in treated cells. Blockage of cell cycle progression was also observed in LF1-treated cells. These findings suggest that LF1 induces apoptosis and cell cycle arrest in treated lung cancer cells. Further studies are being conducted to isolate and identify the active compound as well to better understand the mechanism involved in inducing cell death.

Highlights

  • Cancer has plagued mankind since the beginning of recorded history

  • Mutations in the respiratory epithelium gives rise to lung cancer which can be categorized into two broad groups, small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC). 15% of all lung cancer cases are SCLC which is a highly malignant form of tumour that originates from cells that exhibit neuroendocrine characteristics

  • The remaining 85% of cases fall into the NSCLC category which is broken down into 3 more groups based on their pathologic subtypes, adenocarcinoma, large cell carcinoma and squamous cell carcinoma [3]

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Summary

Introduction

Cancer has plagued mankind since the beginning of recorded history It is a persistent ailment where more than a million people are diagnosed with this disease each year and has a considerably social impact and significant economic burden on our healthcare system. One form of this disease that is severely overlooked is lung cancer which accounts for 19.8% of all medically certified deaths due to cancer in Malaysia [1]. The remaining 85% of cases fall into the NSCLC category which is broken down into 3 more groups based on their pathologic subtypes, adenocarcinoma, large cell carcinoma and squamous cell carcinoma [3]. NSCLC patients have a low survival rate; less than 20% of patients survived beyond 5 years after being diagnosed with the disease [4,5,6]

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