Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin

Cisplatin (Cisp) is a non-specific chemotherapeutic agent for breast cancer. Hesperetin (HST), a flavanone found in various citrus fruits, exhibits bioactive properties, functioning as an antioxidant, anti-inflammatory, and anticancer agent. The objective of this research was to investigate the pote...

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Main Authors: Anif Nur Artanti, Riris Istighfari Jenie, Rumiyati Rumiyati, Edy Meiyanto
Format: Article
Language:English
Published: Indonesian Society for Cancer Chemoprevention 2023-10-01
Series:ISCC (Indonesian Journal of Cancer Chemoprevention)
Online Access:https://ijcc.chemoprev.org/index.php/ijcc/article/view/485
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author Anif Nur Artanti
Riris Istighfari Jenie
Rumiyati Rumiyati
Edy Meiyanto
author_facet Anif Nur Artanti
Riris Istighfari Jenie
Rumiyati Rumiyati
Edy Meiyanto
author_sort Anif Nur Artanti
collection DOAJ
description Cisplatin (Cisp) is a non-specific chemotherapeutic agent for breast cancer. Hesperetin (HST), a flavanone found in various citrus fruits, exhibits bioactive properties, functioning as an antioxidant, anti-inflammatory, and anticancer agent. The objective of this research was to investigate the potential of HST as a co-chemotherapeutic agent in conjunction with Cisp, specifically focusing on its cytotoxic effects against 4T1 triple-negative breast cancer cells and senescence modulatory effect on Vero normal kidney cells. The cytotoxic effect and viability cell of HST were evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. In addition, the effect of cellular senescence inhibition on the Vero cell line was measured using senescence-associated β-galactosidase (SA-β-gal) staining. In the MTT assay, both HST and cisplatin demonstrated a reduction in the viability of 4T1 cells in a dose-dependent manner, yielding IC50 values of 498 μM and 2 μM, respectively. The co-treatment of HST and cisplatin showed an increase in sensitivity of the 4T1 cells with a combination index of <1. HST showed low cytotoxic activity against Vero cells, with IC50 values of over 500 μM. HST decreased cellular senescence induced by cisplatin exposure on Vero cells. These results indicated that HST in co-treatment with cisplatin decreased 4T1 cell viability synergistically. HST independently reduces the cellular senescence of normal cells. Consequently, HST holds promise for potential development as a co-treatment agent in combination with cisplatin for breast cancer cells, and it may also serve as an alternative for counteracting senescence in healthy tissues. Keywords: cytotoxic, senescence, hesperetin, cisplatin, breast cancer.
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series ISCC (Indonesian Journal of Cancer Chemoprevention)
spelling doaj-art-815c6869be5142c09e7ac6f6c7efeea22025-08-20T03:52:14ZengIndonesian Society for Cancer ChemopreventionISCC (Indonesian Journal of Cancer Chemoprevention)2088-01972355-89892023-10-0114318118810.14499/indonesianjcanchemoprev14iss3pp181-188275Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with CisplatinAnif Nur Artanti0Riris Istighfari Jenie1Rumiyati Rumiyati2Edy Meiyanto31) Doctoral Programme in Pharmaceutical Science, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia. 2) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada (UGM), Sekip Utara, Yogyakarta 55281, Indonesia. 3) Department of Pharmacy, Vocational College, Universitas Sebelas Maret Surakarta, Central Java 57126, Indonesia.Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada (UGM), Sekip Utara, Yogyakarta 55281, IndonesiaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada (UGM), Sekip Utara, Yogyakarta 55281, Indonesia.1) Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada. 2) Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, UGM, Sekip Utara, Yogyakarta 55281, Indonesia.Cisplatin (Cisp) is a non-specific chemotherapeutic agent for breast cancer. Hesperetin (HST), a flavanone found in various citrus fruits, exhibits bioactive properties, functioning as an antioxidant, anti-inflammatory, and anticancer agent. The objective of this research was to investigate the potential of HST as a co-chemotherapeutic agent in conjunction with Cisp, specifically focusing on its cytotoxic effects against 4T1 triple-negative breast cancer cells and senescence modulatory effect on Vero normal kidney cells. The cytotoxic effect and viability cell of HST were evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. In addition, the effect of cellular senescence inhibition on the Vero cell line was measured using senescence-associated β-galactosidase (SA-β-gal) staining. In the MTT assay, both HST and cisplatin demonstrated a reduction in the viability of 4T1 cells in a dose-dependent manner, yielding IC50 values of 498 μM and 2 μM, respectively. The co-treatment of HST and cisplatin showed an increase in sensitivity of the 4T1 cells with a combination index of <1. HST showed low cytotoxic activity against Vero cells, with IC50 values of over 500 μM. HST decreased cellular senescence induced by cisplatin exposure on Vero cells. These results indicated that HST in co-treatment with cisplatin decreased 4T1 cell viability synergistically. HST independently reduces the cellular senescence of normal cells. Consequently, HST holds promise for potential development as a co-treatment agent in combination with cisplatin for breast cancer cells, and it may also serve as an alternative for counteracting senescence in healthy tissues. Keywords: cytotoxic, senescence, hesperetin, cisplatin, breast cancer.https://ijcc.chemoprev.org/index.php/ijcc/article/view/485
spellingShingle Anif Nur Artanti
Riris Istighfari Jenie
Rumiyati Rumiyati
Edy Meiyanto
Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
ISCC (Indonesian Journal of Cancer Chemoprevention)
title Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
title_full Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
title_fullStr Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
title_full_unstemmed Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
title_short Cytotoxic Activity and Senescence Modulatory Effect of Hesperetin on Triple-Negative Breast Cancer Cells and Kidney Cells Co-Treatment with Cisplatin
title_sort cytotoxic activity and senescence modulatory effect of hesperetin on triple negative breast cancer cells and kidney cells co treatment with cisplatin
url https://ijcc.chemoprev.org/index.php/ijcc/article/view/485
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