[10]-gingerol increases doxorubicin antitumoural and antimetastatic activity while decreases its undesired side effects in a triple negative breast cancer mouse model


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Ana Carolina Martin1,Rebeka Tomasin1,Marina Naves1,Angelica Graminha1,Liany Luna-Dulcey1,Ramon Teles1,Marcia Cominetti1
1Federal University of São Carlos

Abstract

Background

Cancer is the second leading cause of death worldwide. Triple negative breast cancer (TNBC), which often metastasize to bones, lungs and brain, does not respond to current target therapies, and thus, there are limited treatments available, especially for late stages. The search and development of new treatments for TNBC, with increased effectiveness and less undesired side effects, is essential to treat this disease.

Method

Using a syngeneic orthotopic spontaneous metastasis mouse model (4T1Br4ch6 cells) we have previously shown that [10]-gingerol (5-10mg/kg, ip, daily) has antitumour and antimetastatic activities, reducing lung, bone and brain metastases either when the treatment started in early stages of disease (palpable tumour) or in early-metastatic disease (just post primary tumour resection). Using the same model, we now conducted experiments with both [10]-gingerol (5-10mg/kg, ip, daily) and doxorubicin (3mg/kg, ip, twice a week) separately or combined.

Results

Our preliminary results have shown that, when the combination was used, there was not only additive antitumour and antimetastatic effects, but also a decrease in doxorubicin-induced weight loss and hepatotoxicity (as per indicated by no significant alterations in AST and ALT levels in serum). Additional analysis to elucidate the molecular mechanisms involved in this sensitizing/additive anticancer effect of [10]-gingerol are ongoing. Furthermore, we also intend to evaluate whether [10]-gingerol also reduces doxorubicin-induced heart damage and skeletal muscle wasting.

Conclusion

Taken together, our data indicates that [10]-gingerol could be used as adjuvant/complementary therapy for TNBC, enhancing the anticancer activity and attenuating undesired toxic effects of conventional chemotherapeutic agents.