Suppression of Molecular Targets and Antiproliferative Effect of Citronellal on Triple-Negative Breast Cancer Cells

Abstract

Background: Triple-Negative Breast Cancer (TNBC) requires targeted therapies to better manage and prevent metastatic mammary gland tumors. Due to the resistance problem associated with the approved drugs, researchers are now focusing on phytochemicals for the treatment of TNBC as they possess pleiotropic mode of action and fewer side effects. Objective: To investigate the antiproliferative effect of citronellal on triple-negative breast cancer cells. Method: Anticancer potential of citronellal was explored by employing SRB, MTT, and NRU antiproliferative assay. Further, the effect of citronellal was observed on molecular targets (Tubulin, COX-2, and LOX-5) utilizing in vitro and in silico methods. Furthermore, the efficacy of citronellal was examined on Ehrlich Ascites Carcinoma cells. In addition, the safety profiling of it was observed at 300 and 1000 mg/kg of body weight in mice. Results: Citronellal suppresses the growth of MDA-MB-231 cells by more than 50% in NRU assay and ~41% and 32% in SRB and MTT assay, respectively. Further, citronellal's effect was observed on molecular targets wherein it suppressed LOX-5 activity (IC50 40.63±2.27 μM) and prevented polymerization of microtubule (IC50 63.62 μM). The result was more prominent against LOX-5 as supported by molecular docking interaction studies, but a non-significant effect was observed at the transcriptional level. The efficacy of citronellal was also determined in Ehrlich Ascites Carcinoma (EAC) model, wherein it inhibited the growth of tumor cells (45.97%) at 75 mg/kg of body weight. It was non-toxic up to 1000 mg/kg of body weight in mice and did not cause significant lysis of erythrocytes. Conclusion: These observations could provide experimental support for citronellal to be used as a chemopreventive agent for breast cancer.