In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)

<b>Background/Objectives:</b> Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and p...

Full description

Saved in:
Bibliographic Details
Main Authors: Mehmet Uğur Karabat, Mehmet Cudi Tuncer, İlhan Özdemir
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/18/6/854
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849431821914210304
author Mehmet Uğur Karabat
Mehmet Cudi Tuncer
İlhan Özdemir
author_facet Mehmet Uğur Karabat
Mehmet Cudi Tuncer
İlhan Özdemir
author_sort Mehmet Uğur Karabat
collection DOAJ
description <b>Background/Objectives:</b> Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and pro-apoptotic effects of Hesperidin, alone and in combination with Cisplatin, on the human epidermoid carcinoma cell line A431. <b>Materials and Methods:</b> A431 cells were cultured under standard conditions and treated with different concentrations of Hesperidin and Cisplatin for 48 h. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-3/7 activity assays. Expression levels of Bax, caspase-3/7, and survivin were measured by RT-qPCR. <b>Results:</b> Hesperidin significantly reduced cell viability at both 24 and 48 h. Annexin V/PI staining revealed increased apoptosis, with the highest apoptotic ratio in the Hesperidin + Cisplatin group (<i>p</i> < 0.001). Caspase-3/7 activity was markedly elevated in Hesperidin-treated cells. RT-qPCR showed upregulation of Bax and caspase-3/7 and downregulation of survivin. <b>Conclusions:</b> Hesperidin demonstrated significant cytotoxic and pro-apoptotic effects in A431 cells. When combined with Cisplatin, a synergistic enhancement of apoptosis was observed. These findings support the potential of Hesperidin as a complementary agent in carcinoma therapy, pending further in vivo and clinical validation.
format Article
id doaj-art-0f9b8519db4047ba99203f78a263dc6a
institution Kabale University
issn 1424-8247
language English
publishDate 2025-06-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj-art-0f9b8519db4047ba99203f78a263dc6a2025-08-20T03:27:32ZengMDPI AGPharmaceuticals1424-82472025-06-0118685410.3390/ph18060854In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)Mehmet Uğur Karabat0Mehmet Cudi Tuncer1İlhan Özdemir2Department of Histology and Embryology, Medical Faculty, Dicle University, Diyarbakır 21200, TurkeyDepartment of Anatomy, Faculty of Medicine, Dicle University, Diyarbakır 21200, TurkeyDepartment of Gynecology and Obstetrics, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey<b>Background/Objectives:</b> Melanoma is an aggressive skin cancer with high metastatic potential and poor prognosis in advanced stages. Hesperidin, a natural flavonoid, has shown anticancer properties across various malignancies. This study aimed to evaluate the antiproliferative and pro-apoptotic effects of Hesperidin, alone and in combination with Cisplatin, on the human epidermoid carcinoma cell line A431. <b>Materials and Methods:</b> A431 cells were cultured under standard conditions and treated with different concentrations of Hesperidin and Cisplatin for 48 h. Cell viability was assessed using the MTT assay. Apoptosis was evaluated by Annexin V-FITC/PI staining and caspase-3/7 activity assays. Expression levels of Bax, caspase-3/7, and survivin were measured by RT-qPCR. <b>Results:</b> Hesperidin significantly reduced cell viability at both 24 and 48 h. Annexin V/PI staining revealed increased apoptosis, with the highest apoptotic ratio in the Hesperidin + Cisplatin group (<i>p</i> < 0.001). Caspase-3/7 activity was markedly elevated in Hesperidin-treated cells. RT-qPCR showed upregulation of Bax and caspase-3/7 and downregulation of survivin. <b>Conclusions:</b> Hesperidin demonstrated significant cytotoxic and pro-apoptotic effects in A431 cells. When combined with Cisplatin, a synergistic enhancement of apoptosis was observed. These findings support the potential of Hesperidin as a complementary agent in carcinoma therapy, pending further in vivo and clinical validation.https://www.mdpi.com/1424-8247/18/6/854melanomaHesperidinapoptosiscaspase-3/7MTT
spellingShingle Mehmet Uğur Karabat
Mehmet Cudi Tuncer
İlhan Özdemir
In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
Pharmaceuticals
melanoma
Hesperidin
apoptosis
caspase-3/7
MTT
title In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
title_full In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
title_fullStr In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
title_full_unstemmed In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
title_short In Vitro Evaluation of Cytotoxic and Pro-Apoptotic Effects of Hesperidin Alone and in Combination with Cisplatin on Human Malignant Melanoma Cell Line (A431)
title_sort in vitro evaluation of cytotoxic and pro apoptotic effects of hesperidin alone and in combination with cisplatin on human malignant melanoma cell line a431
topic melanoma
Hesperidin
apoptosis
caspase-3/7
MTT
url https://www.mdpi.com/1424-8247/18/6/854
work_keys_str_mv AT mehmetugurkarabat invitroevaluationofcytotoxicandproapoptoticeffectsofhesperidinaloneandincombinationwithcisplatinonhumanmalignantmelanomacelllinea431
AT mehmetcudituncer invitroevaluationofcytotoxicandproapoptoticeffectsofhesperidinaloneandincombinationwithcisplatinonhumanmalignantmelanomacelllinea431
AT ilhanozdemir invitroevaluationofcytotoxicandproapoptoticeffectsofhesperidinaloneandincombinationwithcisplatinonhumanmalignantmelanomacelllinea431