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Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds

Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. T...

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Main Authors: Mahmud, Israa Ali, Mirghani, Mohamed Elwathig Saeed, Al-Qubaisi, Mothanna, , Beh Yee, Ismail, Norsharina, Rasedee, Abdullah, Yusof, Faridah, Shahabuddin, Munira, Al-khatib, Ma'an, Kabbashi, Nassereldeen Ahmed, Hashim, Yumi Zuhanis Has-Yun, Hilles, Ayah, Abbas, Phirdaous
Format: Article
Language:English
Published: MDPI 2019
Subjects:
T Technology (General)
Online Access:http://irep.iium.edu.my/74977/1/preprints201906.0003.v1.pdf
http://irep.iium.edu.my/74977/
https://www.preprints.org/manuscript/201906.0003/v1
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spelling my.iium.irep.749772019-11-08T07:06:42Z http://irep.iium.edu.my/74977/ Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds Mahmud, Israa Ali Mirghani, Mohamed Elwathig Saeed Al-Qubaisi, Mothanna , Beh Yee Ismail, Norsharina Rasedee, Abdullah Yusof, Faridah Shahabuddin, Munira Al-khatib, Ma'an Kabbashi, Nassereldeen Ahmed Hashim, Yumi Zuhanis Has-Yun Hilles, Ayah Abbas, Phirdaous T Technology (General) Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents. MDPI 2019-06 Article NonPeerReviewed application/pdf en http://irep.iium.edu.my/74977/1/preprints201906.0003.v1.pdf Mahmud, Israa Ali and Mirghani, Mohamed Elwathig Saeed and Al-Qubaisi, Mothanna and , Beh Yee and Ismail, Norsharina and Rasedee, Abdullah and Yusof, Faridah and Shahabuddin, Munira and Al-khatib, Ma'an and Kabbashi, Nassereldeen Ahmed and Hashim, Yumi Zuhanis Has-Yun and Hilles, Ayah and Abbas, Phirdaous (2019) Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds. Preprint. pp. 1-37. (Unpublished) https://www.preprints.org/manuscript/201906.0003/v1 10.20944/preprints201906.0003.v1
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
topic T Technology (General)
spellingShingle T Technology (General)
Mahmud, Israa Ali
Mirghani, Mohamed Elwathig Saeed
Al-Qubaisi, Mothanna
, Beh Yee
Ismail, Norsharina
Rasedee, Abdullah
Yusof, Faridah
Shahabuddin, Munira
Al-khatib, Ma'an
Kabbashi, Nassereldeen Ahmed
Hashim, Yumi Zuhanis Has-Yun
Hilles, Ayah
Abbas, Phirdaous
Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds
description Background and objectives: The initiation of apoptotic death in cancer cells is the aim of many chemotherapeutic strategies. As many anticancer agents have been discovered in natural plant sources, the search for novel phytochemicals displaying anticancer activities continues at a tremendous rate. This study was conducted to evaluate the effect of extractable polyphenols (EPP); non-extractable polyphenols (NEPP); nobiletin (NOB); tectorigenin (TEC) and persicogenin (PERS) from Barhi date palm kernels (BDPK) extracts on the induction of apoptosis in human lung cancer A549 and colon cancer HT29 cell lines. Materials and Methods: The anticancer activities were determined using MTT and trypan blue exclusion assays. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. The underlying mechanism of apoptosis induced by crude extracts and the purified compounds was investigated using caspase-3, -8 and -9 assays and the mitochondrial membrane potential assay. Results: The findings indicate that both BDPK extracts and the purified compounds do exert induced cell death on A549 and HT29 cells. The results observed from MTT- assay and trypan blue exclusion indicate that the cytotoxic effects of both plant extracts and the three isolated flavonoids are dose-dependent with higher cell death after 72 hours treatment. Treatment of human lung and colon cancer cells with EPP, NEPP, NOB, TEC and PERSI induced late stages of apoptosis as there was evidence of the DNA degradation and high percentage of the cells population was situated at sub-G1 phase, indicating a high population of apoptotic cells. Conclusions: Study of the apoptotic mechanism demonstrated that EPP and NEPP exhibited dependent mitochondrial signalling pathway as seen with caspase-9 and induced receptor-mediated (extrinsic) apoptotic pathway as seen with caspase-8. Therefore, our results suggest that BDPK extracts and the three isolated flavonoids could be a good candidate for developing anticancer agents.
format Article
author Mahmud, Israa Ali
Mirghani, Mohamed Elwathig Saeed
Al-Qubaisi, Mothanna
, Beh Yee
Ismail, Norsharina
Rasedee, Abdullah
Yusof, Faridah
Shahabuddin, Munira
Al-khatib, Ma'an
Kabbashi, Nassereldeen Ahmed
Hashim, Yumi Zuhanis Has-Yun
Hilles, Ayah
Abbas, Phirdaous
author_facet Mahmud, Israa Ali
Mirghani, Mohamed Elwathig Saeed
Al-Qubaisi, Mothanna
, Beh Yee
Ismail, Norsharina
Rasedee, Abdullah
Yusof, Faridah
Shahabuddin, Munira
Al-khatib, Ma'an
Kabbashi, Nassereldeen Ahmed
Hashim, Yumi Zuhanis Has-Yun
Hilles, Ayah
Abbas, Phirdaous
author_sort Mahmud, Israa Ali
title Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds
title_short Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds
title_full Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds
title_fullStr Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds
title_full_unstemmed Induction of apoptosis and cell cycle arrest in two human cancer A549 and HT29 cells lines by Barhi date palm kernels extracts and three isolated cytotoxic compounds
title_sort induction of apoptosis and cell cycle arrest in two human cancer a549 and ht29 cells lines by barhi date palm kernels extracts and three isolated cytotoxic compounds
publisher MDPI
publishDate 2019
url http://irep.iium.edu.my/74977/1/preprints201906.0003.v1.pdf
http://irep.iium.edu.my/74977/
https://www.preprints.org/manuscript/201906.0003/v1
_version_ 1651865961299443712
score 13.211869

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