Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B

Geranylated 4-phenylcoumarins DMDP-1 and DMDP-2 isolated from Mesua elegans were elucidated for their role in inducing caspase-independent programmed cell death (CI-PCD) in prostate cancer cell lines, PC-3 and DU 145, respectively. Cell homeostasis disruption was demonstrated upon treatment, as show...

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Main Authors: Sapili, Hani, Ho, Chai San, Malagobadan, Sharan, Arshad, Norhafiza Mohd, Nagoor, Noor Hasima
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Published: Nature Research 2020
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Online Access:http://eprints.um.edu.my/25129/
https://doi.org/10.1038/s41598-020-57781-6
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spelling my.um.eprints.251292020-07-17T04:01:23Z http://eprints.um.edu.my/25129/ Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B Sapili, Hani Ho, Chai San Malagobadan, Sharan Arshad, Norhafiza Mohd Nagoor, Noor Hasima Q Science (General) QH Natural history Geranylated 4-phenylcoumarins DMDP-1 and DMDP-2 isolated from Mesua elegans were elucidated for their role in inducing caspase-independent programmed cell death (CI-PCD) in prostate cancer cell lines, PC-3 and DU 145, respectively. Cell homeostasis disruption was demonstrated upon treatment, as shown by the increase in calcium ion through colourimetric assay and endoplasmic reticulum (ER) stress markers GRP 78 and p-eIF2α through western blot. Subsequently, cytoplasmic death protease calpain-2 also showed increased activity during DMDP-1 & -2 treatments, while lysosomic death protease cathepsin B activity was significantly increased in PC-3 treated with DMDP-1. Flow cytometry showed a reduction in mitochondrial membrane potential in both cell lines, while western blotting showed translocation of mitochondrial death protease AIF into the cytoplasm in its truncated form. Furthermore, DMDP-1 & -2 treatments caused significant increase in superoxide level and oxidative DNA damage. Concurrent inhibition of calpain-2 and cathepsin B during the treatment showed an attenuation of cell death in both cell lines. Hence, DMDP-1 & -2 induce CI-PCD in prostate cancer cell lines through calpain-2 and cathepsin B. © 2020, The Author(s). Nature Research 2020 Article PeerReviewed Sapili, Hani and Ho, Chai San and Malagobadan, Sharan and Arshad, Norhafiza Mohd and Nagoor, Noor Hasima (2020) Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B. Scientific Reports, 10 (1). p. 986. ISSN 2045-2322 https://doi.org/10.1038/s41598-020-57781-6 doi:10.1038/s41598-020-57781-6
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic Q Science (General)
QH Natural history
spellingShingle Q Science (General)
QH Natural history
Sapili, Hani
Ho, Chai San
Malagobadan, Sharan
Arshad, Norhafiza Mohd
Nagoor, Noor Hasima
Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
description Geranylated 4-phenylcoumarins DMDP-1 and DMDP-2 isolated from Mesua elegans were elucidated for their role in inducing caspase-independent programmed cell death (CI-PCD) in prostate cancer cell lines, PC-3 and DU 145, respectively. Cell homeostasis disruption was demonstrated upon treatment, as shown by the increase in calcium ion through colourimetric assay and endoplasmic reticulum (ER) stress markers GRP 78 and p-eIF2α through western blot. Subsequently, cytoplasmic death protease calpain-2 also showed increased activity during DMDP-1 & -2 treatments, while lysosomic death protease cathepsin B activity was significantly increased in PC-3 treated with DMDP-1. Flow cytometry showed a reduction in mitochondrial membrane potential in both cell lines, while western blotting showed translocation of mitochondrial death protease AIF into the cytoplasm in its truncated form. Furthermore, DMDP-1 & -2 treatments caused significant increase in superoxide level and oxidative DNA damage. Concurrent inhibition of calpain-2 and cathepsin B during the treatment showed an attenuation of cell death in both cell lines. Hence, DMDP-1 & -2 induce CI-PCD in prostate cancer cell lines through calpain-2 and cathepsin B. © 2020, The Author(s).
format Article
author Sapili, Hani
Ho, Chai San
Malagobadan, Sharan
Arshad, Norhafiza Mohd
Nagoor, Noor Hasima
author_facet Sapili, Hani
Ho, Chai San
Malagobadan, Sharan
Arshad, Norhafiza Mohd
Nagoor, Noor Hasima
author_sort Sapili, Hani
title Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
title_short Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
title_full Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
title_fullStr Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
title_full_unstemmed Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
title_sort geranylated 4-phenylcoumarins extracted from mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin b
publisher Nature Research
publishDate 2020
url http://eprints.um.edu.my/25129/
https://doi.org/10.1038/s41598-020-57781-6
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