[10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models

[10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models

Purpose Although doxorubicin is widely used to treat cancer, severe side effects limit its clinical use. Combination of standard chemotherapy with natural products can increase the efficacy and attenuate the side effects of current therapies. Here we studied the anticancer effects of a combined regi...

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Bibliographic Details
Published in:Cellular oncology (Dordrecht) Vol. 43; no. 5; pp. 915 - 929
Main Authors: Baptista Moreno Martin, Ana Carolina, Tomasin, Rebeka, Luna-Dulcey, Liany, Graminha, Angélica Elen, Araújo Naves, Marina, Teles, Ramon Handerson Gomes, da Silva, Vinicius Duval, da Silva, James Almada, Vieira, Paulo Cezar, Annabi, Borhane, Cominetti, Márcia Regina
Format: Journal Article
Language:English
Published: Dordrecht Springer Netherlands 01-10-2020
Springer Nature B.V
Subjects:
Antitumor activity
Apoptosis
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Caspase-3
Cell cycle
Chemotherapy
Cytotoxicity
Doxorubicin
Flow cytometry
Hepatotoxicity
Metastases
Natural products
Oncology
Original Paper
Pathology
Side effects
Tumor cells
Tumors
Western blotting
Xenografts
Combined therapies
Metastasis
Gingerol
Doxorubicin
Triple-negative breast cancer
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Summary:Purpose Although doxorubicin is widely used to treat cancer, severe side effects limit its clinical use. Combination of standard chemotherapy with natural products can increase the efficacy and attenuate the side effects of current therapies. Here we studied the anticancer effects of a combined regimen comprising doxorubicin and [10]-gingerol against triple-negative breast cancer, which does not respond to hormonal or targeted therapies. Methods Cytotoxicity was evaluated by MTT assay, cell cycle progression and apoptosis were analyzed by flow cytometry and signaling pathways were analyzed by Western blotting in human and murine triple negative breast cancer cell systems. The anticancer/antimetastatic and toxic effects of the combined regimen was evaluated using syngeneic and xenograft orthotopic models. Results The combination of doxorubicin and [10]-gingerol significantly increased the number of apoptotic cells, compared to each compound alone. In 4T1Br4 cells, the combined regimen was the only condition able to increase the levels of active caspase 3 and γH2AX and to decrease the level of Cdk-6 cyclin. In vivo , doxorubicin (3 mg/Kg, D3) and [10]-gingerol (10 mg/Kg, G10) resulted in a significant reduction in the volume of primary tumors and a decrease in the number of circulating tumor cells (CTCs). Interestingly, only the combined regimen led to decreased tumor burdens to distant organs (i.e., metastasis) and reduced chemotherapy-induced weight loss and hepatotoxicity in tumor-bearing animals. Likewise, in a xenograft model, only the combined regimen was effective in significantly reducing the primary tumor volume and the prevalence of CTCs. Conclusions Our data indicate that [10]-gingerol has potential to be used as a neoadjuvant or in combined therapy with doxorubicin, to improve its anticancer activity.
ISSN:2211-3428
2211-3436
DOI:10.1007/s13402-020-00539-z