Discovery of a Secalonic Acid Derivative from Aspergillus aculeatus, an Endophyte of Rosa damascena Mill., Triggers Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cells

A new secalonic acid derivative, F-7 (1), was isolated from the endophytic Aspergillus aculeatus MBT 102, associated with Rosa damascena. The planar structure of 1 was established on the basis of 1D and 2D NMR and ESI-TOF-MS spectra. The relative configuration of 1 was determined applying a combined quantum mechanical/NMR approach and, afterward, the comparison of calculated and experimental electronic circular dichroism spectra determined the assignment of its absolute configuration. The compound possesses strong cytotoxic activity against triple negative breast cancer (TNBC) cells. It was found to induce apoptosis, as evidenced by scanning electron microscopy and phase contrast microscopy. Furthermore, flow cytometry analyses demonstrated that 1 induced mitochondrial damage and reactive oxygen species mediated apoptosis, arresting the G1 phase of the cells in a dose-dependent manner. Also, the compound causes significant microtubule disruption in TNBC cells. Subsequently, 1 restricted the cell migration leading to the concomitant increase in expression of cleaved caspase and PARP.