[10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDA-MB-231 Breast Tumor Cells

Author(s)

Fuzer, Angelina M. ^[1] ; Martin, Ana C. B. M. ^[1] ; Becceneri, Amanda B. ^[1] ; da Silva, James A. ^[2] ; Vieira, Paulo C. ^[3] ; Cominetti, Marcia R. ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Sergipe, Dept Pharmacol, BR-49100000 Lagarto, SE - Brazil

^[3] Fed Univ Sao Carlos Monjolinho, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 19, n. 5, p. 645-654, 2019.
• Web of Science Citations: 2

Abstract

Background: Triple Negative Breast Cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of Estrogen (ER) and Progesterone Receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene, imposing difficulties to treatment. interactions between tumor cells and their microenvironment facilitate tumor cell invasion in the surrounding tissues, intravasation through newly formed vessels, and dissemination to form metastasis. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in natural antitumor agents. In a previous work, we have demonstrated that {[}10]-gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including lung, bone and brain, in spontaneous and experimental in vivo metastasis assays in mouse model. Objectives: This work aims to investigate the in vitro effects of {[}10]-gingerol, using human MDA-MB-231TNBC cells, in comparison to non-tumor MCF-10A breast cells, in order to understand the antitumor and antimetastatic effects found in vivo and in a 3D environment. Methods: We investigated different steps of the metastatic process in vitro, such as cell migration, invasion, adhesion and MMP activity. In addition, we analyzed the anti-apoptotic and genotoxic effects of {[}10]-gingerol using PE-Annexin, DNA fragmentation, TUNEL and comet assays, respectively. Results: {[}10]-gingerol was able to inhibit cell adhesion, migration, invasion and to induce apoptosis more effectively in TNBC cells, when compared to non-tumor cells, demonstrating that these mechanisms can be involved in the antitumor and antimetastatic effects of {[}10]-gingerol, found both in 3D culture and in vivo. Conclusion: Taken together, results found here are complementary to previous studies of our group and others and demonstrate that additional mechanisms, besides apoptotic cell death, is used by {[}10]-gingeml to accomplish its antitumor and antimetastatic effects. Our results indicate a potential for this natural compound as an antitumor molecule or as an adjuvant for chemotherapeutics already used in the clinic. (AU)

• FAPESP's process: 13/00798-2 - The extracellular matrix in aging, exercise and in the tumor microenvironment
• Grantee: Heloisa Sobreiro Selistre de Araújo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23202-6 - SENSITIZER EFFECTS AND MECHANISMS OF ACTION OF [10]-GINGEROL IN COMBINATION WITH DOXORUBICIN FOR BREAST CANCER TREATMENT: IN VITRO AND IN VIVO STUDIES
• Grantee: Ana Carolina Baptista Moreno Martin
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/24940-8 - EFFECTIVENESS OF STRUCTURAL CHANGES IN [10]-GINGEROL MOLECULE IN COMBINATION WITH THE CHEMOTHERAPEUTIC DOXORUBICIN FOR THE TREATMENT OF BREAST CANCER: IN VITRO AND IN VIVO STUDIES. ABSTRACT
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Regular Research Grants