Synergistic cotreatment potential of soursop (Annona muricata l.) leaves extract with doxorubicin on 4t1 cells with antisenescence and anti-reactive-oxygen-species properties

Salsabila, Irfani Aura and Nugraheni, Nadzifa and Ahlina, Faradiba Nur and Haryanti, Sari and Meiyanto, Edy (2021) Synergistic cotreatment potential of soursop (Annona muricata l.) leaves extract with doxorubicin on 4t1 cells with antisenescence and anti-reactive-oxygen-species properties. Iranian Journal of Pharmaceutical Research, 20 (2). 57 – 67. ISSN 17350328

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Abstract

Annona muricata L. extract (AME) exhibits cytotoxic activities on various types of cancer cells. This study aims to unveil the anticancer activity of AME as a cotreatment agent with doxorubicin (dox) on 4T1 cells and AME’s relation to senescence. AME was obtained by maceration using 96 ethanol. AME was then subjected to qualitative analysis using TLC compared to quercetin (hRf = 75). Spectrophotometry analysis of AME resulted in a total flavonoid content of 2.3 ± 0.05. Cytotoxic evaluation using the MTT assay revealed that AME showed an IC50 value of 63 µg/mL, while its combination (25 µg/mL) with dox (10 nM) decreased the viability of 4T1 cells to 58 (CI = 0.15). Flowcytometry using propidium iodide staining confirmed that AME (13 and 25 µg/mL) caused cell cycle arrest in the G1 phase as a single treatment and G2/M arrest in combination with dox. However, by using the dichloro dihydrofluorescein diacetate staining assay, it turned out that AME at concentrations of 13 and 25 µg/mL decreased intracellular reactive oxygen species (ROS) levels both as a single treatment and in combination with dox. Senescence-associated β-galactosidase assay showed that AME decreased dox-induced senescence. AME alone and in combination with dox (cotreatment) showed cytotoxic effect synergistically on 4T1 cells, but this was not caused by an increase in intracellular ROS levels as well as senescence induction. Therefore, AME showed its potential to be a cotreatment agent with antioxidant property on triple-negative breast cancer cells. © 2021, Iranian Journal of Pharmaceutical Research. All rights reserved.

Item Type: Article
Additional Information: Cited by: 12
Uncontrolled Keywords: antioxidant; beta galactosidase; doxorubicin; flavonoid; lactate dehydrogenase; plant extract; protein Bax; quercetin; reactive oxygen metabolite; 4T1 cell line; Annona muricata; antineoplastic activity; antioxidant activity; antiproliferative activity; apoptosis; Article; breast cancer; cancer cell; cancer stem cell; cell culture; cell cycle; cell cycle arrest; cell cycle G1 phase; cell cycle progression; cell growth; cell proliferation; cell viability; chromatography; controlled study; cytotoxicity; DPPH radical scavenging assay; drug potentiation; enzyme linked immunosorbent assay; flow cytometry; G2 phase cell cycle checkpoint; human; human cell; IC50; MTT assay; nonhuman; oxidative stress; plant leaf; progression free survival; qualitative analysis; senescence; spectrophotometry; synergistic effect; thin layer chromatography
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy
Depositing User: Sri JUNANDI
Date Deposited: 20 Sep 2024 01:57
Last Modified: 20 Sep 2024 01:57
URI: https://ir.lib.ugm.ac.id/id/eprint/4807

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