Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells

Currently, global efforts are being intensified towards the discovery of local Bacillus thuringiensis (Bt) isolates with unique anticancer properties. Parasporins (PS) are a group of Bt non-insecticidal crystal proteins with potential and specific in vitro anticancer activity. However, despite the s...

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Main Authors:	Aboul-Soud, Mourad A.M., Al-Amri, Mohammed Z., Kumar, Ashok, Al-Sheikh, Yazeed A., Ashour, Abdelkader Elbadawy Abbas, El-Kersh, Talaat A.
Format:	Article
Language:	English English English
Published:	Multidisciplinary Digital Publishing Institute (MDPI) 2019
Subjects:	HC94 By region or country RC270 Neoplasms. Tumors. Oncology-Cancer and Other Malignant Neoplasms-Therapeutics
Online Access:	http://irep.iium.edu.my/70427/ http://irep.iium.edu.my/70427/ http://irep.iium.edu.my/70427/ http://irep.iium.edu.my/70427/1/Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal%20Proteins%20Isolated%20from%20Native%20Saudi%20Arabian%20Bacillus%20thuringiensis%20Strains%20against%20Cervical%20Cancer%20Cells.pdf http://irep.iium.edu.my/70427/7/70427_Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal_wos.pdf http://irep.iium.edu.my/70427/8/70427_Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal_scopus.pdf

id	iium-70427
recordtype	eprints
spelling	iium-704272019-07-31T06:45:05Z http://irep.iium.edu.my/70427/ Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells Aboul-Soud, Mourad A.M. Al-Amri, Mohammed Z. Kumar, Ashok Al-Sheikh, Yazeed A. Ashour, Abdelkader Elbadawy Abbas El-Kersh, Talaat A. HC94 By region or country RC270 Neoplasms. Tumors. Oncology-Cancer and Other Malignant Neoplasms-Therapeutics Currently, global efforts are being intensified towards the discovery of local Bacillus thuringiensis (Bt) isolates with unique anticancer properties. Parasporins (PS) are a group of Bt non-insecticidal crystal proteins with potential and specific in vitro anticancer activity. However, despite the significant therapeutic potential of PS-producing Bt strains, our current knowledge on the effects of these proteins is limited. Hence, the main objective of this study was to screen Bt-derived parasporal toxins for cytotoxic activities against colon (HT-29) and cervical (HeLa) cancerous cell lines. Nine non-larvicidal and non-hemolytic Bt strains, native to Saudi Arabia, were employed for the isolation of their parasporal toxins. 16S rDNA sequencing revealed a 99.5% similarity with a reference Bt strain. While PCR screening results indicated the absence of selected Cry (Cry4A, Cry4B, Cry10 and Cry11), Cyt (Cyt1 and Cyt2) and PS (PS2, PS3 and PS4) genes, it concluded presence of the PS1 gene. SDS-PAGE analysis revealed that proteolytically-cleavaged PS protein profiles exhibit patterns resembling those observed with PS1Aa1, with major bands at 56 kDa and 17 kDa (Bt7), and 41 kDa and 16 kDa (Bt5). Solubilized and trypsinized PS proteins from all Bt strains exhibited a marked and dose-dependent cytotoxicity against HeLa cancerous cells but not against HT-29 cells. IC50 values ranged from 3.2 (Bt1) to 14.2 (Bt6) with an average of 6.8 µg/mL. The observed cytotoxicity of PS proteins against HeLa cells was specific as it was not evident against normal uterus smooth muscle cells. RT-qPCR analysis revealed the overexpression of caspase 3 and caspase 9 by 3.7, and 4.2 folds, respectively, indicative of the engagement of intrinsic pathway of apoptosis. To the best of our knowledge, this is the first report exploring and exploiting the versatile repertoire of Saudi Arabian environmental niches for the isolation of native and possibly novel Saudi Bt strains with unique and specific anticancer activity. In conclusion, native Saudi Bt-derived PS proteins might have a potential to join the arsenal of natural anticancer drugs. Multidisciplinary Digital Publishing Institute (MDPI) 2019-02-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/70427/1/Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal%20Proteins%20Isolated%20from%20Native%20Saudi%20Arabian%20Bacillus%20thuringiensis%20Strains%20against%20Cervical%20Cancer%20Cells.pdf application/pdf en http://irep.iium.edu.my/70427/7/70427_Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal_wos.pdf application/pdf en http://irep.iium.edu.my/70427/8/70427_Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal_scopus.pdf Aboul-Soud, Mourad A.M. and Al-Amri, Mohammed Z. and Kumar, Ashok and Al-Sheikh, Yazeed A. and Ashour, Abdelkader Elbadawy Abbas and El-Kersh, Talaat A. (2019) Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells. Molecules, 24 (3). pp. 1-16. ISSN 1420-3049 https://www.mdpi.com/search?authors=Talat%20%20A.%20El-Kersh&orcid= 10.3390/molecules24030506
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	HC94 By region or country RC270 Neoplasms. Tumors. Oncology-Cancer and Other Malignant Neoplasms-Therapeutics
spellingShingle	HC94 By region or country RC270 Neoplasms. Tumors. Oncology-Cancer and Other Malignant Neoplasms-Therapeutics Aboul-Soud, Mourad A.M. Al-Amri, Mohammed Z. Kumar, Ashok Al-Sheikh, Yazeed A. Ashour, Abdelkader Elbadawy Abbas El-Kersh, Talaat A. Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells
description	Currently, global efforts are being intensified towards the discovery of local Bacillus thuringiensis (Bt) isolates with unique anticancer properties. Parasporins (PS) are a group of Bt non-insecticidal crystal proteins with potential and specific in vitro anticancer activity. However, despite the significant therapeutic potential of PS-producing Bt strains, our current knowledge on the effects of these proteins is limited. Hence, the main objective of this study was to screen Bt-derived parasporal toxins for cytotoxic activities against colon (HT-29) and cervical (HeLa) cancerous cell lines. Nine non-larvicidal and non-hemolytic Bt strains, native to Saudi Arabia, were employed for the isolation of their parasporal toxins. 16S rDNA sequencing revealed a 99.5% similarity with a reference Bt strain. While PCR screening results indicated the absence of selected Cry (Cry4A, Cry4B, Cry10 and Cry11), Cyt (Cyt1 and Cyt2) and PS (PS2, PS3 and PS4) genes, it concluded presence of the PS1 gene. SDS-PAGE analysis revealed that proteolytically-cleavaged PS protein profiles exhibit patterns resembling those observed with PS1Aa1, with major bands at 56 kDa and 17 kDa (Bt7), and 41 kDa and 16 kDa (Bt5). Solubilized and trypsinized PS proteins from all Bt strains exhibited a marked and dose-dependent cytotoxicity against HeLa cancerous cells but not against HT-29 cells. IC50 values ranged from 3.2 (Bt1) to 14.2 (Bt6) with an average of 6.8 µg/mL. The observed cytotoxicity of PS proteins against HeLa cells was specific as it was not evident against normal uterus smooth muscle cells. RT-qPCR analysis revealed the overexpression of caspase 3 and caspase 9 by 3.7, and 4.2 folds, respectively, indicative of the engagement of intrinsic pathway of apoptosis. To the best of our knowledge, this is the first report exploring and exploiting the versatile repertoire of Saudi Arabian environmental niches for the isolation of native and possibly novel Saudi Bt strains with unique and specific anticancer activity. In conclusion, native Saudi Bt-derived PS proteins might have a potential to join the arsenal of natural anticancer drugs.
format	Article
author	Aboul-Soud, Mourad A.M. Al-Amri, Mohammed Z. Kumar, Ashok Al-Sheikh, Yazeed A. Ashour, Abdelkader Elbadawy Abbas El-Kersh, Talaat A.
author_facet	Aboul-Soud, Mourad A.M. Al-Amri, Mohammed Z. Kumar, Ashok Al-Sheikh, Yazeed A. Ashour, Abdelkader Elbadawy Abbas El-Kersh, Talaat A.
author_sort	Aboul-Soud, Mourad A.M.
title	Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells
title_short	Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells
title_full	Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells
title_fullStr	Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells
title_full_unstemmed	Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells
title_sort	specific cytotoxic effects of parasporal crystal proteins isolated from native saudi arabian bacillus thuringiensis strains against cervical cancer cells
publisher	Multidisciplinary Digital Publishing Institute (MDPI)
publishDate	2019
url	http://irep.iium.edu.my/70427/ http://irep.iium.edu.my/70427/ http://irep.iium.edu.my/70427/ http://irep.iium.edu.my/70427/1/Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal%20Proteins%20Isolated%20from%20Native%20Saudi%20Arabian%20Bacillus%20thuringiensis%20Strains%20against%20Cervical%20Cancer%20Cells.pdf http://irep.iium.edu.my/70427/7/70427_Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal_wos.pdf http://irep.iium.edu.my/70427/8/70427_Specific%20Cytotoxic%20Effects%20of%20Parasporal%20Crystal_scopus.pdf
first_indexed	2023-09-18T21:39:59Z
last_indexed	2023-09-18T21:39:59Z
_version_	1777413075053314048

Specific cytotoxic effects of parasporal crystal proteins isolated from native Saudi Arabian bacillus thuringiensis strains against cervical cancer cells

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