In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells

Lung cancer specifically non-small cell lung cancer (NSCLC) is one of the most devastating cancers. Despite having diverse treatment methods such as surgery, chemotherapy, radiation and targeted therapies, the overall 5-year survival rate for NSCLC is accounted for only 18.2 %. The high mortality ra...

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Main Author:	Mohamad Rosdi, Mohamad Norisham
Format:	Thesis
Language:	English
Published:	2019
Subjects:	TP Chemical technology
Online Access:	http://eprints.utm.my/id/eprint/85985/1/MohamadNorishamPSCHE2019.pdf
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spelling	my-utm-ep.859852020-08-30T08:48:55Z In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells 2019 Mohamad Rosdi, Mohamad Norisham TP Chemical technology Lung cancer specifically non-small cell lung cancer (NSCLC) is one of the most devastating cancers. Despite having diverse treatment methods such as surgery, chemotherapy, radiation and targeted therapies, the overall 5-year survival rate for NSCLC is accounted for only 18.2 %. The high mortality rates for NSCLC are partially due to the lack of effective prognostic factors such as biomarkers. Nowadays, plantderived bioactive substances have been making way as potential anticancer agents. One such plant is Annona muricata Linn, which is also known as soursop or graviola. This plant has been widely reported to contain valuable phytochemical substances that could be developed as chemopreventive agents. The antiproliferative and anticancer activities of this tropical plant have been demonstrated in in vitro cell culture studies as well as in in vivo studies of animals. It has been discovered that A. muricata L. extract exerts inhibition against various number of cancer cells, involving multiple mechanism of actions. Nonetheless, the mode of action and the molecular interactions of the plant have not yet been unveiled for most of these mechanisms. In the current study, response surface methodology was utilized to optimize the ultrasonic-assisted extraction (UAE) and maceration extraction (ME) of A. muricata L. leaves. Central composite design was applied to optimize the antioxidant activity of both extracts. It has been found that ME extract showed high antioxidant activity as compared to UAE extract with 83.3 % and 31.6 % respectively. However, through cytotoxicity study that was done by using M TT assay, UAE extract exhibited significant cytotoxicity effects in NSCLC cell line (HLFa) with IC50 of 139.6 p,g/mL as compared to ME extract with IC30 of 108.4 p,g/mL. The effect of the extracts on nitric oxide (NO) production in HLFa cells was also evaluated using Griess reagent system assay. Both extracts reduced the release of nitrite in the cell supernatant which indicated the reduction in NO production. Caspase 3/7 apoptosis assay was used to detect the presence of apoptotic machinery in HLFa cells after incubation. The mRNA expression of several genes namely HMGB1, BCL2 and BAX were quantified. The mechanistic evalution of the results showed the possibility of involvement of these genes in A. muricata L. anticancer effects. At the end of this study, in silico molecular docking interaction of several phytoconstituents of A. muricata L. was analysed against Bcl-2 antiapoptotic proteins namely Bcl-2, Bcl-w and Mcl-1. The stability of complexes formed was evaluated using molecular dynamic simulation. Anonaine was also detected in UAE and ME extracts through HPLC screening process with 10.6 ppm and 10.7 ppm, respectively. 2019 Thesis http://eprints.utm.my/id/eprint/85985/ http://eprints.utm.my/id/eprint/85985/1/MohamadNorishamPSCHE2019.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:131500 phd doctoral Universiti Teknologi Malaysia, Faculty of Engineering - School of Chemical & Energy Engineering Faculty of Engineering - School of Chemical & Energy Engineering
institution	Universiti Teknologi Malaysia
collection	UTM Institutional Repository
language	English
topic	TP Chemical technology
spellingShingle	TP Chemical technology Mohamad Rosdi, Mohamad Norisham In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells
description	Lung cancer specifically non-small cell lung cancer (NSCLC) is one of the most devastating cancers. Despite having diverse treatment methods such as surgery, chemotherapy, radiation and targeted therapies, the overall 5-year survival rate for NSCLC is accounted for only 18.2 %. The high mortality rates for NSCLC are partially due to the lack of effective prognostic factors such as biomarkers. Nowadays, plantderived bioactive substances have been making way as potential anticancer agents. One such plant is Annona muricata Linn, which is also known as soursop or graviola. This plant has been widely reported to contain valuable phytochemical substances that could be developed as chemopreventive agents. The antiproliferative and anticancer activities of this tropical plant have been demonstrated in in vitro cell culture studies as well as in in vivo studies of animals. It has been discovered that A. muricata L. extract exerts inhibition against various number of cancer cells, involving multiple mechanism of actions. Nonetheless, the mode of action and the molecular interactions of the plant have not yet been unveiled for most of these mechanisms. In the current study, response surface methodology was utilized to optimize the ultrasonic-assisted extraction (UAE) and maceration extraction (ME) of A. muricata L. leaves. Central composite design was applied to optimize the antioxidant activity of both extracts. It has been found that ME extract showed high antioxidant activity as compared to UAE extract with 83.3 % and 31.6 % respectively. However, through cytotoxicity study that was done by using M TT assay, UAE extract exhibited significant cytotoxicity effects in NSCLC cell line (HLFa) with IC50 of 139.6 p,g/mL as compared to ME extract with IC30 of 108.4 p,g/mL. The effect of the extracts on nitric oxide (NO) production in HLFa cells was also evaluated using Griess reagent system assay. Both extracts reduced the release of nitrite in the cell supernatant which indicated the reduction in NO production. Caspase 3/7 apoptosis assay was used to detect the presence of apoptotic machinery in HLFa cells after incubation. The mRNA expression of several genes namely HMGB1, BCL2 and BAX were quantified. The mechanistic evalution of the results showed the possibility of involvement of these genes in A. muricata L. anticancer effects. At the end of this study, in silico molecular docking interaction of several phytoconstituents of A. muricata L. was analysed against Bcl-2 antiapoptotic proteins namely Bcl-2, Bcl-w and Mcl-1. The stability of complexes formed was evaluated using molecular dynamic simulation. Anonaine was also detected in UAE and ME extracts through HPLC screening process with 10.6 ppm and 10.7 ppm, respectively.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Mohamad Rosdi, Mohamad Norisham
author_facet	Mohamad Rosdi, Mohamad Norisham
author_sort	Mohamad Rosdi, Mohamad Norisham
title	In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells
title_short	In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells
title_full	In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells
title_fullStr	In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells
title_full_unstemmed	In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells
title_sort	in vitro and in silico anticancer activities of annona muricata linn leaves extracts on lung cancer cells
granting_institution	Universiti Teknologi Malaysia, Faculty of Engineering - School of Chemical & Energy Engineering
granting_department	Faculty of Engineering - School of Chemical & Energy Engineering
publishDate	2019
url	http://eprints.utm.my/id/eprint/85985/1/MohamadNorishamPSCHE2019.pdf
_version_	1747818478037893120

In vitro and in silico anticancer activities of Annona muricata linn leaves extracts on lung cancer cells

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