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Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line

Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of M...

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Main Authors: Tan, Bee Ling, Mohd Esa, Norhaizan
Format: Article
Language:English
Published: Elsevier 2019
Online Access:http://psasir.upm.edu.my/id/eprint/81279/1/APOP.pdf
http://psasir.upm.edu.my/id/eprint/81279/
https://www.sciencedirect.com/science/article/pii/S075333221834349X?via%3Dihub
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spelling my.upm.eprints.812792021-06-14T23:42:52Z http://psasir.upm.edu.my/id/eprint/81279/ Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line Tan, Bee Ling Mohd Esa, Norhaizan Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of Manilkara zapota leaf water extract have yet to be investigated thus far. Therefore, our present study aimed to evaluate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf water extract against human colorectal cancer (HT-29) cells. The cytotoxicity of Manilkara zapota leaf water extract was screened in different cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. The morphological changes in HT-29 cell lines after exposure to Manilkara zapota leaf water extract were viewed under fluorescence and inverted light microscope. The apoptotic cell was measured by Annexin V-propidium iodide staining. The caspase-3 and -8 activities were assessed by colorimetric assay. Overall analyses revealed that treatment with Manilkara zapota leaf water extract for 72 h can inhibit the viability of HT-29 cells. Incubation with Manilkara zapota leaf water extract for 24, 48, and 72 h significantly increased (p < 0.05) the total apoptotic cells compared to the control. Treatment with 21, 42, and 84 μg/mL of Manilkara zapota leaf water extract for 72 h triggered both caspase-3 and -8 activities in a concentration-dependent pattern. We also found that the catalase level in the two treatment groups (21 and 42 μg/mL) was significantly elevated after 24 h incubation. Incubation with Manilkara zapota leaf water extract for 72 h triggered the transcriptional elevation of the adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), AXIN1, and casein kinase 1 (CK1). The β-catenin mRNA levels were reduced accordingly when the concentration of the Manilkara zapota leaf water extract was increased. Our results suggested that Manilkara zapota leaf water extract offer great potential against colorectal cancer through modulation of Wnt/β-catenin signaling pathway, caspase-dependent pathway, and antioxidant enzyme. Elsevier 2019-02 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/81279/1/APOP.pdf Tan, Bee Ling and Mohd Esa, Norhaizan (2019) Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line. Biomedicine and Pharmacotherapy, 110. pp. 748-757. ISSN 0753-3322 https://www.sciencedirect.com/science/article/pii/S075333221834349X?via%3Dihub 10.1016/j.biopha.2018.12.027
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 Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of Manilkara zapota leaf water extract have yet to be investigated thus far. Therefore, our present study aimed to evaluate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf water extract against human colorectal cancer (HT-29) cells. The cytotoxicity of Manilkara zapota leaf water extract was screened in different cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. The morphological changes in HT-29 cell lines after exposure to Manilkara zapota leaf water extract were viewed under fluorescence and inverted light microscope. The apoptotic cell was measured by Annexin V-propidium iodide staining. The caspase-3 and -8 activities were assessed by colorimetric assay. Overall analyses revealed that treatment with Manilkara zapota leaf water extract for 72 h can inhibit the viability of HT-29 cells. Incubation with Manilkara zapota leaf water extract for 24, 48, and 72 h significantly increased (p < 0.05) the total apoptotic cells compared to the control. Treatment with 21, 42, and 84 μg/mL of Manilkara zapota leaf water extract for 72 h triggered both caspase-3 and -8 activities in a concentration-dependent pattern. We also found that the catalase level in the two treatment groups (21 and 42 μg/mL) was significantly elevated after 24 h incubation. Incubation with Manilkara zapota leaf water extract for 72 h triggered the transcriptional elevation of the adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), AXIN1, and casein kinase 1 (CK1). The β-catenin mRNA levels were reduced accordingly when the concentration of the Manilkara zapota leaf water extract was increased. Our results suggested that Manilkara zapota leaf water extract offer great potential against colorectal cancer through modulation of Wnt/β-catenin signaling pathway, caspase-dependent pathway, and antioxidant enzyme.
format Article
author Tan, Bee Ling
Mohd Esa, Norhaizan
spellingShingle Tan, Bee Ling
Mohd Esa, Norhaizan
Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line
author_facet Tan, Bee Ling
Mohd Esa, Norhaizan
author_sort Tan, Bee Ling
title Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line
title_short Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line
title_full Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line
title_fullStr Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line
title_full_unstemmed Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line
title_sort manilkara zapota (l.) p. royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in ht-29 human colorectal cancer cell line
publisher Elsevier
publishDate 2019
url http://psasir.upm.edu.my/id/eprint/81279/1/APOP.pdf
http://psasir.upm.edu.my/id/eprint/81279/
https://www.sciencedirect.com/science/article/pii/S075333221834349X?via%3Dihub
_version_ 1703962154848223232
score 13.211869

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