Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis

Ovarian cancer is a deadly disease with a poor prognosis, highlighting the urgent need for novel therapeutic alternatives. Pyranocycloartobiloxanthone A (PA), an exceptional xanthone compound has garnered attention due to its diverse medicinal properties. This study aimed to investigate the anticanc...

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Main Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Idris Adewale Ahmed
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2023
Online Access:http://journalarticle.ukm.my/23364/
http://journalarticle.ukm.my/23364/1/SD%2015.pdf
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author Mashitoh Abd Rahman,
Najihah Mohd Hashim,
Idris Adewale Ahmed,
author_facet Mashitoh Abd Rahman,
Najihah Mohd Hashim,
Idris Adewale Ahmed,
author_sort Mashitoh Abd Rahman,
building UKM Institutional Repository
collection Online Access
description Ovarian cancer is a deadly disease with a poor prognosis, highlighting the urgent need for novel therapeutic alternatives. Pyranocycloartobiloxanthone A (PA), an exceptional xanthone compound has garnered attention due to its diverse medicinal properties. This study aimed to investigate the anticancer properties of PA on metastatic ovarian cancer SKOV-3 cells. Cytotoxicity was evaluated using an MTT assay, while apoptotic mechanisms were determined using AO/PI double staining, annexin V-fluorescein isothiocyanate, multiple cytotoxicity-3, reactive oxygen species (ROS) production, caspases, real-time PCR, western blot, human apoptosis protein profile array and cell cycle analysis. PA inhibited SKOV-3 cell proliferation in a time-dependent manner, with an IC50 of 7.0 ± 0.5 µg/mL and a selectivity index of 13.2 after 72 h of treatment. PA induced apoptosis through the intrinsic apoptotic pathway and arrested the cell cycle at the S phase. PA stimulated ROS production and disrupted the mitochondrial membrane potential, releasing cytochrome c from mitochondria to the cytosol. Additionally, results from human apoptotic protein profile indicated that 21 proteins were upregulated while 22 proteins were downregulated, including Bcl-2, survivin, and HSP70. These findings suggest that PA has the potential as a lead molecule in the development of a chemotherapy drug for ovarian cancer. However, further research is necessary to evaluate the safety and efficacy of PA in preclinical and clinical settings.
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spelling oai:generic.eprints.org:233642024-04-17T08:08:50Z http://journalarticle.ukm.my/23364/ Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis Mashitoh Abd Rahman, Najihah Mohd Hashim, Idris Adewale Ahmed, Ovarian cancer is a deadly disease with a poor prognosis, highlighting the urgent need for novel therapeutic alternatives. Pyranocycloartobiloxanthone A (PA), an exceptional xanthone compound has garnered attention due to its diverse medicinal properties. This study aimed to investigate the anticancer properties of PA on metastatic ovarian cancer SKOV-3 cells. Cytotoxicity was evaluated using an MTT assay, while apoptotic mechanisms were determined using AO/PI double staining, annexin V-fluorescein isothiocyanate, multiple cytotoxicity-3, reactive oxygen species (ROS) production, caspases, real-time PCR, western blot, human apoptosis protein profile array and cell cycle analysis. PA inhibited SKOV-3 cell proliferation in a time-dependent manner, with an IC50 of 7.0 ± 0.5 µg/mL and a selectivity index of 13.2 after 72 h of treatment. PA induced apoptosis through the intrinsic apoptotic pathway and arrested the cell cycle at the S phase. PA stimulated ROS production and disrupted the mitochondrial membrane potential, releasing cytochrome c from mitochondria to the cytosol. Additionally, results from human apoptotic protein profile indicated that 21 proteins were upregulated while 22 proteins were downregulated, including Bcl-2, survivin, and HSP70. These findings suggest that PA has the potential as a lead molecule in the development of a chemotherapy drug for ovarian cancer. However, further research is necessary to evaluate the safety and efficacy of PA in preclinical and clinical settings. Penerbit Universiti Kebangsaan Malaysia 2023 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/23364/1/SD%2015.pdf Mashitoh Abd Rahman, and Najihah Mohd Hashim, and Idris Adewale Ahmed, (2023) Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis. Sains Malaysiana, 52 (12). pp. 3533-3550. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol52num12_2023/contentsVol52num12_2023.html
spellingShingle Mashitoh Abd Rahman,
Najihah Mohd Hashim,
Idris Adewale Ahmed,
Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
title Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
title_full Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
title_fullStr Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
title_full_unstemmed Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
title_short Pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
title_sort pyranocycloartobiloxanthone a suppressed metastasis ovarian cancer cells via s phase cell cycle arrest and apoptosis
url http://journalarticle.ukm.my/23364/
http://journalarticle.ukm.my/23364/
http://journalarticle.ukm.my/23364/1/SD%2015.pdf