Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction

Doxorubicin is a chemotherapeutic agent that causes a lot of side effects in high doses. Thus, combination with a co-chemotherapeutic agent which can increase its toxicity on cancer cells, is needed to reduce its therapeutic dose. Red betel leaves (Piper crocatum Ruiz & Pav.) have been known to ...

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Main Authors: Nindi Wulandari, Argandita Meiftasari, Hilyatul Fadliyah, Riris Istighfari Jenie
Format: Article
Language:English
Published: Indonesian Society for Cancer Chemoprevention 2018-02-01
Series:ISCC (Indonesian Journal of Cancer Chemoprevention)
Online Access:https://ijcc.chemoprev.org/index.php/ijcc/article/view/197
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author Nindi Wulandari
Argandita Meiftasari
Hilyatul Fadliyah
Riris Istighfari Jenie
author_facet Nindi Wulandari
Argandita Meiftasari
Hilyatul Fadliyah
Riris Istighfari Jenie
author_sort Nindi Wulandari
collection DOAJ
description Doxorubicin is a chemotherapeutic agent that causes a lot of side effects in high doses. Thus, combination with a co-chemotherapeutic agent which can increase its toxicity on cancer cells, is needed to reduce its therapeutic dose. Red betel leaves (Piper crocatum Ruiz & Pav.) have been known to contain flavonoids and alkaloids that have anticancer activity. This study was conducted to determine the cytotoxic effect and apoptosis induction of red betel leaves methanolic extract (RBM), doxorubicin (dox) and the combination of them on WiDr cells as model of colon cancer. RBM was extracted by soxhlet method using methanol. Cytotoxicity assay was performed using MTT assay for both single and combination treatments for 24 hours to determine IC50 and CI as their parameters. Apoptosis induction was analyzed by double staining method using ethidium bromide-acridine orange staining. Treatment of RBM and dox on WiDr cells for 24 hours showed cytotoxic activity with IC50 100 μg/mL and 1.6 μM respectively. Combination of RBM and dox performed synergism effect with CI<0.9 (p<0.05). Combination of RBM (12.5 μg/mL) and dox (0.4 μM) increased the number of apoptosis cells compared to each single treatment. Based on this study, it can be concluded that red betel leaves methanolic extract is potential to be developed as a co-chemotherapeutic agent of doxorubicin on colon cancer but still need further study to disclose the underlying molecular mechanisms. Keywords :  Red betel leaves (Piper crocatum Ruiz & Pav.), doxorubicin, WiDr cells, co- chemotherapeutic agent
format Article
id doaj-art-9b9da95db1624b46935ed43f75fdd951
institution Kabale University
issn 2088-0197
2355-8989
language English
publishDate 2018-02-01
publisher Indonesian Society for Cancer Chemoprevention
record_format Article
series ISCC (Indonesian Journal of Cancer Chemoprevention)
spelling doaj-art-9b9da95db1624b46935ed43f75fdd9512025-08-20T03:49:07ZengIndonesian Society for Cancer ChemopreventionISCC (Indonesian Journal of Cancer Chemoprevention)2088-01972355-89892018-02-01911810.14499/indonesianjcanchemoprev9iss1pp1-8158Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis InductionNindi Wulandari0Argandita Meiftasari1Hilyatul Fadliyah2Riris Istighfari Jenie3Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah MadaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah MadaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah MadaDepartement of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah MadaDoxorubicin is a chemotherapeutic agent that causes a lot of side effects in high doses. Thus, combination with a co-chemotherapeutic agent which can increase its toxicity on cancer cells, is needed to reduce its therapeutic dose. Red betel leaves (Piper crocatum Ruiz & Pav.) have been known to contain flavonoids and alkaloids that have anticancer activity. This study was conducted to determine the cytotoxic effect and apoptosis induction of red betel leaves methanolic extract (RBM), doxorubicin (dox) and the combination of them on WiDr cells as model of colon cancer. RBM was extracted by soxhlet method using methanol. Cytotoxicity assay was performed using MTT assay for both single and combination treatments for 24 hours to determine IC50 and CI as their parameters. Apoptosis induction was analyzed by double staining method using ethidium bromide-acridine orange staining. Treatment of RBM and dox on WiDr cells for 24 hours showed cytotoxic activity with IC50 100 μg/mL and 1.6 μM respectively. Combination of RBM and dox performed synergism effect with CI<0.9 (p<0.05). Combination of RBM (12.5 μg/mL) and dox (0.4 μM) increased the number of apoptosis cells compared to each single treatment. Based on this study, it can be concluded that red betel leaves methanolic extract is potential to be developed as a co-chemotherapeutic agent of doxorubicin on colon cancer but still need further study to disclose the underlying molecular mechanisms. Keywords :  Red betel leaves (Piper crocatum Ruiz & Pav.), doxorubicin, WiDr cells, co- chemotherapeutic agenthttps://ijcc.chemoprev.org/index.php/ijcc/article/view/197
spellingShingle Nindi Wulandari
Argandita Meiftasari
Hilyatul Fadliyah
Riris Istighfari Jenie
Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction
ISCC (Indonesian Journal of Cancer Chemoprevention)
title Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction
title_full Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction
title_fullStr Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction
title_full_unstemmed Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction
title_short Red Betel Leaves Methanolic Extract (Piper crocatum Ruiz & Pav.) Increases Cytotoxic Effect of Doxorubicin on WiDr Colon Cancer Cells through Apoptosis Induction
title_sort red betel leaves methanolic extract piper crocatum ruiz pav increases cytotoxic effect of doxorubicin on widr colon cancer cells through apoptosis induction
url https://ijcc.chemoprev.org/index.php/ijcc/article/view/197
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AT arganditameiftasari redbetelleavesmethanolicextractpipercrocatumruizpavincreasescytotoxiceffectofdoxorubicinonwidrcoloncancercellsthroughapoptosisinduction
AT hilyatulfadliyah redbetelleavesmethanolicextractpipercrocatumruizpavincreasescytotoxiceffectofdoxorubicinonwidrcoloncancercellsthroughapoptosisinduction
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