ArticleAsian Pacific journal of cancer prevention : APJCP2020
Cytotoxic and Antimetastatic Activity of Hesperetin and Doxorubicin Combination Toward Her2 Expressing Breast Cancer Cells.
Article in Asian Pacific journal of cancer prevention : APJCP, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Flavonoid-Based Combination Therapies and Nano-Formulations: An Emerging Frontier in Breast Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Updated Review on Natural Polyphenols: Molecular Mechanisms, Biological Effects, and Clinical Applications for Cancer Management.Biomolecules · 2025Review
- Citrus flavonoids for overcoming breast cancer resistance to methotrexate: identification of potential targets of nobiletin and sinensetin.Discover oncology · 2025Article
- Multifaced Anticancer Potential of Doxorubicin: Spotlight on Breast Cancer.Diseases & research · 2025Article
- Article
- The effect of hesperetin on estrogen receptor gene expression and its relationship with the downstream pathways of estrogen receptor alpha.Molecular biology reports · 2023Article
- Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer.Journal of cellular and molecular medicine · 2023Article
- In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells.Journal of the Egyptian National Cancer Institute · 2023Article
- Lupeol synergizes with doxorubicin to induce anti-proliferative and apoptotic effects on breast cancer cells.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022Article
- Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha.Frontiers in oncology · 2022Review
- Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review.Heliyon · 2022Review
- Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects.Saudi journal of biological sciences · 2021Review
- RepCOOL: computational drug repositioning via integrating heterogeneous biological networks.Journal of translational medicine · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis study aimed to explore Hesperetin (Hst) potency as a co-chemotherapeutics agent combined with Doxorubicin (Dox), particularly cytotoxic and antimetastasis effects toward MCF-7/HER2 cells.
methodsThe cytotoxic effects were measured under MTT assay. The flowcytometry analysis was used to examine the cell cycle modulation and apoptosis evidence, while the effect of migration was assayed by scratch wound healing assay. Western blotting and gelatin zymography were carried out to examine the expression level of proteins, HER2, and Rac1.
resultsUnder MTT assay, Hst and Dox exhibited to decrease cell viability in a dose-dependent manner with the IC50 value of 377 and 0,8 µM, respectively. The combination of Hst and Dox at the respective doses of 95 and 0,2 µM showed a synergistic effect with the combination index of 0,63. Flow cytometry analysis of Hst-Dox revealed that those compounds caused cell cycle arrest at the G2/M phase and induced apoptosis. Hst also decreased HER2 and Rac1 expression, as shown by western blot. Hst inhibited lamellipodia formation and cell migration, as indicated by microscopic observation and wound healing scratch assay. The antimetastatic activity of Hst was associated with the reduction of Rac1 and MMP9 expression as measured by gelatine zymography assay.
conclusionThese results indicated that the combination of Hst and Dox-induced cell cycle arrest, apoptosis, decreased HER2, Rac1, MMP9 expression, and cell migration. Thus, Hst may have the potential to be developed as a co-chemotherapeutic agent combined with doxorubicin toward HER2 overexpressing breast cancer cells.
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