Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D

Pentagamavunone-1 (PGV-1), a curcumin analog, is a promising anticancer candidate for several cancers that have been proven in vitro and in vivo. However, the efficacy of PGV-1 against breast cancer is subject to improvement to achieve a more suitable application. Here we propose hesperitin, a citru...

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Main Authors: Fauziah Novita Putri Rifai, Mila Hanifa, Ummi Maryam Zulfin, Muthi Ikawati, Edy Meiyanto
Format: Article
Language:English
Published: Universitas Gadjah Mada 2024-03-01
Series:Journal of Tropical Biodiversity and Biotechnology
Subjects:
Online Access:https://journal.ugm.ac.id/jtbb/article/view/88238
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author Fauziah Novita Putri Rifai
Mila Hanifa
Ummi Maryam Zulfin
Muthi Ikawati
Edy Meiyanto
author_facet Fauziah Novita Putri Rifai
Mila Hanifa
Ummi Maryam Zulfin
Muthi Ikawati
Edy Meiyanto
author_sort Fauziah Novita Putri Rifai
collection DOAJ
description Pentagamavunone-1 (PGV-1), a curcumin analog, is a promising anticancer candidate for several cancers that have been proven in vitro and in vivo. However, the efficacy of PGV-1 against breast cancer is subject to improvement to achieve a more suitable application. Here we propose hesperitin, a citrus flavonoid, to increase the anticancer potency of PGV-1 in luminal breast cancer cells. We use the T47D cell as the model to investigate the effect of co-administration of PGV-1 and hesperitin on cell cycle block, apoptosis modulation, and senescence phenomena. PGV-1 and hesperitin showed strong and weak cytotoxicity with an IC50 value of 2 µM and 100 µM, respectively. The co-treatment of PGV-1 and hesperitin resulted in strong synergistic effects with combination index (CI) value of ≤ 0.2. This combination caused apoptosis in correlation with cell cycle disruption in G2/M phase at 48 h. In particular, PGV-1 and hesperitin combination increased the incidence of cellular senescence significantly higher than the single treatment. Despite its senescence potentiation, hesperitin did not induce senescence in normal cells. Taken together, hesperitin may increase the anticancer potency of PGV-1 by modulating cell cycle arrest and apoptosis via the senescence mechanism.
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spelling doaj.art-8cafec5714ee467e9eb9c6a6df1c45f52024-03-21T03:30:47ZengUniversitas Gadjah MadaJournal of Tropical Biodiversity and Biotechnology2540-95732540-95812024-03-019110.22146/jtbb.8823835460Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47DFauziah Novita Putri Rifai0Mila Hanifa1Ummi Maryam Zulfin2Muthi Ikawati3Edy Meiyanto4Master of Biotechnology Study Program, Graduate School, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia; Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia; Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaCancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada; Macromolecular Engineering Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, IndonesiaPentagamavunone-1 (PGV-1), a curcumin analog, is a promising anticancer candidate for several cancers that have been proven in vitro and in vivo. However, the efficacy of PGV-1 against breast cancer is subject to improvement to achieve a more suitable application. Here we propose hesperitin, a citrus flavonoid, to increase the anticancer potency of PGV-1 in luminal breast cancer cells. We use the T47D cell as the model to investigate the effect of co-administration of PGV-1 and hesperitin on cell cycle block, apoptosis modulation, and senescence phenomena. PGV-1 and hesperitin showed strong and weak cytotoxicity with an IC50 value of 2 µM and 100 µM, respectively. The co-treatment of PGV-1 and hesperitin resulted in strong synergistic effects with combination index (CI) value of ≤ 0.2. This combination caused apoptosis in correlation with cell cycle disruption in G2/M phase at 48 h. In particular, PGV-1 and hesperitin combination increased the incidence of cellular senescence significantly higher than the single treatment. Despite its senescence potentiation, hesperitin did not induce senescence in normal cells. Taken together, hesperitin may increase the anticancer potency of PGV-1 by modulating cell cycle arrest and apoptosis via the senescence mechanism.https://journal.ugm.ac.id/jtbb/article/view/88238hesperitincurcumin analogsynergistic effectsenescencet47d cells.
spellingShingle Fauziah Novita Putri Rifai
Mila Hanifa
Ummi Maryam Zulfin
Muthi Ikawati
Edy Meiyanto
Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D
Journal of Tropical Biodiversity and Biotechnology
hesperitin
curcumin analog
synergistic effect
senescence
t47d cells.
title Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D
title_full Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D
title_fullStr Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D
title_full_unstemmed Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D
title_short Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D
title_sort hesperitin synergistically promotes the senescence induction of pentagamavunone 1 in luminal breast cancer cells t47d
topic hesperitin
curcumin analog
synergistic effect
senescence
t47d cells.
url https://journal.ugm.ac.id/jtbb/article/view/88238
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