Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of...

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Main Authors:	Muhammad Nazirul Mubin, Aziz, Yazmin, Hussin, Nurul Fattin, Che Rahim, Noraini, Nordin, Nurul Elyani, Mohamad, Swee, Keong Yeap, Chean, Yeah Yong, Akhtar, Muhammad Nadeem, Mas Jaffri, Masarudin, Yoke, Kqueen Cheah, Nadiah, Abu, Noorjahan Banu, Alitheen
Format:	Article
Language:	English
Published:	MDPI - Open Access Publishing 2018
Subjects:	Q Science (General) T Technology (General)
Online Access:	http://umpir.ump.edu.my/id/eprint/20313/ http://umpir.ump.edu.my/id/eprint/20313/ http://umpir.ump.edu.my/id/eprint/20313/ http://umpir.ump.edu.my/id/eprint/20313/1/Curcumin%20Analog%20DK1%20Induces%20Apoptosis%20in%20Human%20Osteosarcoma%20Cells%20In%20Vitro%20through%20Mitochondria%20Dependent%20Signaling%20Pathway.pdf

id	ump-20313
recordtype	eprints
spelling	ump-203132019-01-23T08:08:26Z http://umpir.ump.edu.my/id/eprint/20313/ Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway Muhammad Nazirul Mubin, Aziz Yazmin, Hussin Nurul Fattin, Che Rahim Noraini, Nordin Nurul Elyani, Mohamad Swee, Keong Yeap Chean, Yeah Yong Akhtar, Muhammad Nadeem Mas Jaffri, Masarudin Yoke, Kqueen Cheah Nadiah, Abu Noorjahan Banu, Alitheen Q Science (General) T Technology (General) Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of the natural substances that have been extensively studied due to its anti-cancer properties and is pharmacologically safe considering its ubiquitous consumption for centuries. However, curcumin suffers from a poor circulating bioavailability, which has led to the development of a chemically synthesized curcuminoid analog, namely (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1). In this study, the cytotoxic effects of the curcumin analog DK1 was investigated in both U-2OS and MG-63 osteosarcoma cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death was microscopically examined via acridine orange/propidium iodide (AO/PI) double staining. Flow cytometer analysis including Annexin V/Fluorescein isothiocyanate (FITC), cell cycle analysis and JC-1 were adapted to determine the mode of cell death. Subsequently in order to determine the mechanism of cell death, quantitative polymerase chain reaction (qPCR) and proteome profiling was carried out to measure the expression of several apoptotic-related genes and proteins. Results indicated that DK1 induced U-2 OS and MG-63 morphological changes and substantially reduced cell numbers through induction of apoptosis. Several apoptotic genes and proteins were steadily expressed after treatment with DK1; including caspase 3, caspase 9, and BAX, which indicated that apoptosis occurred through a mitochondria-dependent signaling pathway. In conclusion, DK1 could be considered as a potential candidate for an anti-osteosarcoma drug in the near future, contingent upon its ability to induce apoptosis in osteosarcoma cell lines. MDPI - Open Access Publishing 2018 Article PeerReviewed pdf en cc_by_4 http://umpir.ump.edu.my/id/eprint/20313/1/Curcumin%20Analog%20DK1%20Induces%20Apoptosis%20in%20Human%20Osteosarcoma%20Cells%20In%20Vitro%20through%20Mitochondria%20Dependent%20Signaling%20Pathway.pdf Muhammad Nazirul Mubin, Aziz and Yazmin, Hussin and Nurul Fattin, Che Rahim and Noraini, Nordin and Nurul Elyani, Mohamad and Swee, Keong Yeap and Chean, Yeah Yong and Akhtar, Muhammad Nadeem and Mas Jaffri, Masarudin and Yoke, Kqueen Cheah and Nadiah, Abu and Noorjahan Banu, Alitheen (2018) Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway. Molecules, 23 (1). pp. 1-15. ISSN 1420-3049 (print); 1420-3049 (online) https://doi.org/10.3390/molecules23010075 https://doi.org/10.3390/molecules23010075
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Malaysia Pahang
building	UMP Institutional Repository
collection	Online Access
language	English
topic	Q Science (General) T Technology (General)
spellingShingle	Q Science (General) T Technology (General) Muhammad Nazirul Mubin, Aziz Yazmin, Hussin Nurul Fattin, Che Rahim Noraini, Nordin Nurul Elyani, Mohamad Swee, Keong Yeap Chean, Yeah Yong Akhtar, Muhammad Nadeem Mas Jaffri, Masarudin Yoke, Kqueen Cheah Nadiah, Abu Noorjahan Banu, Alitheen Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway
description	Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of the natural substances that have been extensively studied due to its anti-cancer properties and is pharmacologically safe considering its ubiquitous consumption for centuries. However, curcumin suffers from a poor circulating bioavailability, which has led to the development of a chemically synthesized curcuminoid analog, namely (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1). In this study, the cytotoxic effects of the curcumin analog DK1 was investigated in both U-2OS and MG-63 osteosarcoma cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death was microscopically examined via acridine orange/propidium iodide (AO/PI) double staining. Flow cytometer analysis including Annexin V/Fluorescein isothiocyanate (FITC), cell cycle analysis and JC-1 were adapted to determine the mode of cell death. Subsequently in order to determine the mechanism of cell death, quantitative polymerase chain reaction (qPCR) and proteome profiling was carried out to measure the expression of several apoptotic-related genes and proteins. Results indicated that DK1 induced U-2 OS and MG-63 morphological changes and substantially reduced cell numbers through induction of apoptosis. Several apoptotic genes and proteins were steadily expressed after treatment with DK1; including caspase 3, caspase 9, and BAX, which indicated that apoptosis occurred through a mitochondria-dependent signaling pathway. In conclusion, DK1 could be considered as a potential candidate for an anti-osteosarcoma drug in the near future, contingent upon its ability to induce apoptosis in osteosarcoma cell lines.
format	Article
author	Muhammad Nazirul Mubin, Aziz Yazmin, Hussin Nurul Fattin, Che Rahim Noraini, Nordin Nurul Elyani, Mohamad Swee, Keong Yeap Chean, Yeah Yong Akhtar, Muhammad Nadeem Mas Jaffri, Masarudin Yoke, Kqueen Cheah Nadiah, Abu Noorjahan Banu, Alitheen
author_facet	Muhammad Nazirul Mubin, Aziz Yazmin, Hussin Nurul Fattin, Che Rahim Noraini, Nordin Nurul Elyani, Mohamad Swee, Keong Yeap Chean, Yeah Yong Akhtar, Muhammad Nadeem Mas Jaffri, Masarudin Yoke, Kqueen Cheah Nadiah, Abu Noorjahan Banu, Alitheen
author_sort	Muhammad Nazirul Mubin, Aziz
title	Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway
title_short	Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway
title_full	Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway
title_fullStr	Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway
title_full_unstemmed	Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway
title_sort	curcumin analog dk1 induces apoptosis in human osteosarcoma cells in vitro through mitochondria-dependent signaling pathway
publisher	MDPI - Open Access Publishing
publishDate	2018
url	http://umpir.ump.edu.my/id/eprint/20313/ http://umpir.ump.edu.my/id/eprint/20313/ http://umpir.ump.edu.my/id/eprint/20313/ http://umpir.ump.edu.my/id/eprint/20313/1/Curcumin%20Analog%20DK1%20Induces%20Apoptosis%20in%20Human%20Osteosarcoma%20Cells%20In%20Vitro%20through%20Mitochondria%20Dependent%20Signaling%20Pathway.pdf
first_indexed	2023-09-18T22:29:13Z
last_indexed	2023-09-18T22:29:13Z
_version_	1777416173223149568

Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

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