Combination of Conventional Drugs with Biocompounds Derived from Cinnamic Acid: A Promising Option for Breast Cancer Therapy

Abstract

Despite the options available for breast cancer (BC) therapy, several adverse effects and resistance limit the success of the treatment. Furthermore, the use of a single drug is associated with a high failure rate. We investigated through a systematic review the in vitro effects of the combination between conventional drugs and bioactive compounds derived from cinnamic acid in BC treatment. The information was acquired from the following databases: PubMed, Web of Science, Embase, Scopus, Lilacs and Cochrane library. We focused on "Cinnamates", "Drug Combinations" and "Breast neoplasms" for publications dating between January 2012 and December 2022, based on the PRISMA statement. The references of the articles were carefully reviewed. Finally, nine eligible studies were included. The majority of these studies were performed using MCF-7, MDA-MB-231, MDA-MB-468 and BT-20 cell lines and the combination between cisplatin, paclitaxel, doxorubicin, tamoxifen, dactolisib and veliparib, with caffeic acid phenethyl ester, eugenol, 3-caffeoylquinic acid, salvianolic acid A, ferulic acid, caffeic acid, rosmarinic acid and ursolic acid. The combination improved overall conventional drug effects, with increased cytotoxicity, antimigratory effect and reversing resistance. Combining conventional drugs with bioactive compounds derived from cinnamic acid could emerge as a privileged scaffold for establishing new treatment options for different BC types.

Keywords: breast neoplasms; cinnamates; drug combinations; drug synergism; therapeutics.

Figure 4

Drugs and biocompounds derived from cinnamic acid studied in vitro as combination therapy for BC.

Figure 1

Main molecular and histological breast cancer subtypes. Abbreviations: DCIS, ductal carcinoma in situ; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; PR, progesterone receptor.

Figure 2

Flow chart of the article selection process.

Figure 3

Summary of the main molecular mechanisms affected by the combination of conventional drugs and bioactive compounds derived from cinnamic acid. Abbreviations: Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma-2; CK7, Cytokeratin 7; CXCR4, C-X-C chemokine receptor type 4; FOXO3a, forkhead box O3; LC3BII, microtubule associated protein 1 light chain 3 beta II; MMP-9, Matrix metallopeptidase 9; MMP-2, Matrix metallopeptidase 2; NF-κB, nuclear factor kappa B; VEGF, vascular endothelial growth factor.