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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: Aziz, Muhammad Nazirul Mubin, Hussin, Yazmin, Che Rahim, Nurul Fattin, Nordin, Noraini, Mohamad, Nurul Elyani, Yeap, Swee Keong, Yong, Chean Yeah, Masarudin, Mas Jaffri, Cheah, Yoke Kqueen, Abu, Nadiah, Akhtar, Muhammad Nadeem, Mohammed Alitheen, Noorjahan Banu
Format: Article
Language:English
Published: M D P I AG 2018
Online Access:http://psasir.upm.edu.my/id/eprint/72154/1/Curcumin%20analog%20DK1%20induces%20apoptosis%20in%20human%20osteosarcoma%20cells%20in%20vitro%20through%20mitochondria-dependent%20signaling%20pathway.pdf
http://psasir.upm.edu.my/id/eprint/72154/
https://www.mdpi.com/1420-3049/23/1/75
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spelling my.upm.eprints.721542020-03-04T08:34:53Z http://psasir.upm.edu.my/id/eprint/72154/ Curcumin analog DK1 induces apoptosis in human osteosarcoma cells in vitro through mitochondria-dependent signaling pathway Aziz, Muhammad Nazirul Mubin Hussin, Yazmin Che Rahim, Nurul Fattin Nordin, Noraini Mohamad, Nurul Elyani Yeap, Swee Keong Yong, Chean Yeah Masarudin, Mas Jaffri Cheah, Yoke Kqueen Abu, Nadiah Akhtar, Muhammad Nadeem Mohammed Alitheen, Noorjahan Banu 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. M D P I AG 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/72154/1/Curcumin%20analog%20DK1%20induces%20apoptosis%20in%20human%20osteosarcoma%20cells%20in%20vitro%20through%20mitochondria-dependent%20signaling%20pathway.pdf Aziz, Muhammad Nazirul Mubin and Hussin, Yazmin and Che Rahim, Nurul Fattin and Nordin, Noraini and Mohamad, Nurul Elyani and Yeap, Swee Keong and Yong, Chean Yeah and Masarudin, Mas Jaffri and Cheah, Yoke Kqueen and Abu, Nadiah and Akhtar, Muhammad Nadeem and Mohammed Alitheen, Noorjahan Banu (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; ESSN: 1420-3049 https://www.mdpi.com/1420-3049/23/1/75 10.3390/molecules23010075
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
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 Aziz, Muhammad Nazirul Mubin
Hussin, Yazmin
Che Rahim, Nurul Fattin
Nordin, Noraini
Mohamad, Nurul Elyani
Yeap, Swee Keong
Yong, Chean Yeah
Masarudin, Mas Jaffri
Cheah, Yoke Kqueen
Abu, Nadiah
Akhtar, Muhammad Nadeem
Mohammed Alitheen, Noorjahan Banu
spellingShingle Aziz, Muhammad Nazirul Mubin
Hussin, Yazmin
Che Rahim, Nurul Fattin
Nordin, Noraini
Mohamad, Nurul Elyani
Yeap, Swee Keong
Yong, Chean Yeah
Masarudin, Mas Jaffri
Cheah, Yoke Kqueen
Abu, Nadiah
Akhtar, Muhammad Nadeem
Mohammed Alitheen, Noorjahan Banu
Curcumin analog DK1 induces apoptosis in human osteosarcoma cells in vitro through mitochondria-dependent signaling pathway
author_facet Aziz, Muhammad Nazirul Mubin
Hussin, Yazmin
Che Rahim, Nurul Fattin
Nordin, Noraini
Mohamad, Nurul Elyani
Yeap, Swee Keong
Yong, Chean Yeah
Masarudin, Mas Jaffri
Cheah, Yoke Kqueen
Abu, Nadiah
Akhtar, Muhammad Nadeem
Mohammed Alitheen, Noorjahan Banu
author_sort Aziz, Muhammad Nazirul Mubin
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 M D P I AG
publishDate 2018
url http://psasir.upm.edu.my/id/eprint/72154/1/Curcumin%20analog%20DK1%20induces%20apoptosis%20in%20human%20osteosarcoma%20cells%20in%20vitro%20through%20mitochondria-dependent%20signaling%20pathway.pdf
http://psasir.upm.edu.my/id/eprint/72154/
https://www.mdpi.com/1420-3049/23/1/75
_version_ 1662756481626275840
score 13.211869

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