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
Authors: Asha Chaubey
Arem Qayum
Maria Giovanna Chini
Asif Ali
Yedukondalu Nalli
Syed Riyaz-Ul-Hassan
Sadaqat Farooq
Shashank K Singh
Giuseppe Bifulco
Gianluigi Lauro
Journal: ACS Omega (2020)
Discipline: CHEMISTRY
Keywords: Secalonic acid derivative; Aspergillus aculeatus; cytotoxic activity; triple negative breast cancer; apoptosis
Affiliations: Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar 190 005, India, Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India, Natural Product Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India, Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, Fisciano 84084, Italy, Department of Biosciences and Territory, University of Molise, Contrada Fonte Lappone, Pesche, Isernia I-86090, Italy, Fermentation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi 180 001, India

Abstract:  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. 

Retracted: No

PubPeer comments:
 The authors describe the cytotoxic activity a Secalonic Acid Derivative in breast cancer cell line and also try to describe its mechanism of action. They say that it inhibits microtubule polymerization as a result of an immunofluorescence-based assay following 48 hours of treatment with the compound. There are several problems with this figure 1. They say they used paclitaxel as a positive control for microtubule depolymerization. Paclitaxel in fact is a microtubule-stabilizing agent and not a depolymerizing agent. And when they treat cells with paclitaxel (50nM) for 48 hours, none of the cells is arrested in mitosis (rounded up) which is practically impossible (Figure 7B). When you treat cells with 50nM paclitaxel for 48 hours, almost all the cells should round up. ![file] 2. The size of the nuclei and merge is different in the figure and instead of 100um, they write 100uM ![file] 3. Any drug that interferes with microtubules will arrest the cells in mitosis (G2 M phase of the cell cycle). However, the authors show that their compound arrests cells in the G1 phase of the cell cycle! which is not possible. How would a mitotic drug arrest cells in the G1 phase? ,