Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells.

Wan Nur Baitty Wan Mohd Tajuddin,Faridah Abas,Rakesh Naidu,Iekhsan Othman

doi:10.3390/ijms22147424

Wan Nur Baitty Wan Mohd Tajuddin, Faridah Abas + Show 2 more

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https://doi.org/10.3390/ijms22147424

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Abstract

Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520—DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2—and NCI-H23 cells—HGF, MET, COL5A2, MCM7, and GNG4—were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.

Highlights

Introduction distributed under the terms andLung cancer is the most commonly diagnosed cancer worldwide with a high mortality rate [1]
The results indicated that treatment with the MS13 demonstrated greater antiproliferative activity on NCI-H520 and NCI-H23 cells compared to curcumin in time- and dose-dependent manner
Our study showed that MS13 exhibited greater cytotoxicity and growth inhibitory effect in a dose-dependent manner at lower concentrations compared to the parent compound, curcumin, in both NCI-H520 and NCI-H23 cells

Summary

Introduction

Introduction distributed under the terms andLung cancer is the most commonly diagnosed cancer worldwide with a high mortality rate [1]. Lung cancer is grouped into two main types: non-small cell lung cancer (NSCLC). NSCLC is the most common type of lung cancer, representing approximately 80% of all lung cancer cases compared to SCLC (20%). The main risk factor of both NSCLC and SCLC is tobacco smoking, with 80–90% of lung cancer patients have smoking history [3]. The standard treatments for both NSCLC and SCLC patients are surgery, chemotherapy, radiation therapy, or a combination of these treatments [4]. Several side effects and toxicities of chemotherapy and radiation therapy have been reported in lung cancer patients [4,5]. There is a need to identify more effective and non-toxic therapeutic drugs for the treatment of lung cancer patients

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