Cytotoxic and Antimetastatic Activity of Hesperetin and Doxorubicin Combination Toward Her2 Expressing Breast Cancer Cells

Nurhayati, Ika Putri; Khumaira, Annisa; Ilmawati, Gagas Pradani Nur; Meiyanto, Edy; Hermawan, Adam

doi:10.31557/apjcp.2020.21.5.1259

Cited by 21 publications

(16 citation statements)

References 20 publications

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“…The chemosensitising activity of hesperetin has also been reported by Nurhayati et al (2020) . In the study, the co-adminstration of doxorubicin and hesperetin exerted greater cytotoxic, G2/M phase arrest-inducing and pro-apoptotic effects against a HER2-overexpressing BC cell line (i.e., MCF-7/HER2) in comparison to either treatment alone.…”

Section: Chemosensitising Activities Of Hesperidin and Hesperetinmentioning

confidence: 72%

Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Yap

Sekar

et al. 2021

Saudi Journal of Biological Sciences

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Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro . They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo . Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.

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Section: Chemosensitising Activities Of Hesperidin and Hesperetinmentioning

confidence: 72%

Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Yap

Sekar

et al. 2021

Saudi Journal of Biological Sciences

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“…CSP is a natural herbal medicine which proven to have a cytotoxic effect on several cancer cells. Hesperetin, a one of secondary metabolite of CSP show to enhance the effect of DOX against HER2+ BC cells [10]. Hesperidin is also enhanced the effectiveness of DOX and 5-FU through apoptosis induction [11], [21].…”

Section: Discussionmentioning

confidence: 99%

“…Flavonoid from Citrus sinensis proven to have an anticancer activity with multiple target side on several type of cancer. Hesperetin, a secondary metabolite of C. sinensis inhibited Rac-1 expression, the expression of a gene that regulated metastatic [10]. Hesperidin is also shown to be inhibited MCF-7 cancer cell grow [11].…”

Section: Introductionmentioning

confidence: 97%

Citrus sinensis (L) Peels Extract Inhibits Metastasis of Breast Cancer Cells by Targeting the Downregulation Matrix Metalloproteinases-9

Suzery

Cahyono

Amalina

2021

Open Access Maced J Med Sci

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Introduction: Long-term use of doxorubicin (DOX) chemotherapy causes several side effects, especially induction of metastasis on breast cancer (BC). There is an urgent need to identify novel agent with low side effect targeting BC metastasis. Citrus sinensis (L.) peels extract (CSP) has long been used for the treatment of several cancer. However, its anti-metastatic potential against BC metastatic remains unclear. Objective: This study aimed to explore the role of CSP in combination with DOX in inhibiting the migration of metastatic breast cancer MDAMB-231 cells. Material and Methods: Potential cytotoxic in single and combination was analysed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay). The anti-metastatic activities of several major compound on CSP including hesperetin, tangeretin, nobiletin, naringenin and hesperidin were screened by molecular docking under PLANTS software. Results: Based on molecular docking we revealed that the selected protein target MMP-9 (PBD ID:2OVX) has lower docking score for hesperetin, tangeretin, nobiletin, naringenin and hesperidin compare to DOX. CSP and DOX individually exhibited strong cytotoxic effect on MDA-MB-231 cells under MTT assay with IC50 value of 344 µg/mL and 85 nM, respectively. Furthermore, CSP in combination with DOX synergistically increased the cytotoxicity of DOX. Here, we showed that CSP can specifically suppress the side effect of DOX-induced metastasis by reduces doses of DOX. However, low doses of DOX in combination with CSP still potential inhibited cancer cells growth. Conclusion: In conclusion, CSP increased the cytotoxicity and inhibited the induction of metastasis by DOX in breast cancer cells. So that, CSP potential to be developed as co-chemotherapeutic agent.

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“…7, the half maximal inhibitory concentration (IC 50 ) of Tamoxifen was 32.13 µM on BT474 cells. It should be noted that the toxic effect of two drugs including, Doxorubicin and Paclitaxel has been proved on MCF-7, SKBR-3 and MCF-7 cell lines, respectively, by other researchers [27][28][29][30]. Therefore, we can consider Tamoxifen and other repurposed molecules as effective drugs for breast cancer.…”

Section: Cell Toxicitymentioning

confidence: 98%

RepCOOL: computational drug repositioning via integrating heterogeneous biological networks

et al. 2020

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Background It often takes more than 10 years and costs more than 1 billion dollars to develop a new drug for a particular disease and bring it to the market. Drug repositioning can significantly reduce costs and time in drug development. Recently, computational drug repositioning attracted a considerable amount of attention among researchers, and a plethora of computational drug repositioning methods have been proposed. This methodology has widely been used in order to address various medical challenges, including cancer treatment. The most common cancers are lung and breast cancers. Thus, suggesting FDA-approved drugs via drug repositioning for breast cancer would help us to circumvent the approval process and subsequently save money as well as time. Methods In this study, we propose a novel network-based method, named RepCOOL, for drug repositioning. RepCOOL integrates various heterogeneous biological networks to suggest new drug candidates for a given disease. Results The proposed method showed a promising performance on benchmark datasets via rigorous cross-validation. The final drug repositioning model has been built based on a random forest classifier after examining various machine learning algorithms. Finally, in a case study, four FDA approved drugs were suggested for breast cancer stage II. Conclusion Results show the potency of the proposed method in detecting true drug-disease relationships. RepCOOL suggested four new drugs for breast cancer stage II namely Doxorubicin, Paclitaxel, Trastuzumab, and Tamoxifen.

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Cytotoxic and Antimetastatic Activity of Hesperetin and Doxorubicin Combination Toward Her2 Expressing Breast Cancer Cells

Cited by 21 publications

References 20 publications

Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Citrus sinensis (L) Peels Extract Inhibits Metastasis of Breast Cancer Cells by Targeting the Downregulation Matrix Metalloproteinases-9

RepCOOL: computational drug repositioning via integrating heterogeneous biological networks

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