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


  • Meiny Suzery Department of Chemistry, Faculty of Sciences and Mathematics, Diponegoro University, Semarang, Indonesia
  • Bambang Cahyono Department of Chemistry, Faculty of Sciences and Mathematics, Diponegoro University, Semarang, Indonesia
  • Nur Dina Amalina Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Semarang State University, Semarang, Indonesia



Citrus sinensis, Co-chemotherapy, Matrix metalloproteinases-9, Metastasis, MDA-MB-231 breast cancer cells



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.


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.


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.


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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How to Cite

Suzery M, Cahyono B, Amalina ND. Citrus sinensis (L) Peels Extract Inhibits Metastasis of Breast Cancer Cells by Targeting the Downregulation Matrix Metalloproteinases-9. Open Access Maced J Med Sci [Internet]. 2021 Jun. 27 [cited 2021 Sep. 20];9(B):464-9. Available from: