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Diarylpentanoid BP-M345 acts as an antimitotic agent in NCI-H460 cell line
1 , 1, 2 , 3, 4 , 3, 4 , 5 , 3, 4 , * 3, 4 , * 1
1  UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
2  TOXRUN—Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal
3  Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
4  Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos, s/n, 4450-208 Matosinhos, Portugal
5  GreenUPorto (Sustainable Agrifood Production) Research Center, Faculty of Sciences, University of Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal
Academic Editor: Alfredo Berzal-Herranz (registering DOI)

Diarylpentanoids comprise a class of natural products and their synthetic analogues well known for their antitumor activity. Recently, the diarylpentanoid BP-M345 has been identified as a potent in vitro growth inhibitor of human colon cancer HCT116 cells expressing wt p53, with a GI50 value of 0.17 µM, showing low toxicity in non-tumor HFF-1 cells. However, it was observed that BP-M345 has no effect on the inhibition of the p53-MDM2 interaction. Further insights into the mechanisms through which this compound could exert growth inhibitor activity were pursued. Considering that BP-M345 possesses 3,4,5-trimethoxyphenyl groups that have been much highlighted as playing crucial role in the interaction with tubulin in MTAs, it was hypothesized that this diarylpentanoid could also act as a antimitotic agent. Its antiproliferative activity was evaluated in human tumor cell line by sulforhodamine B assay. BP-M345 promoted a prolonged SAC-dependent mitotic arrest by interfering with mitotic spindle assembly, followed by massive apoptosis. The overall results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, highlighting its potential as antitumor agent. Additionally, docking poses and residues involved in the binding site of α,β-tubulin were predicted by docking studies.

Keywords: diarylpentanoid; BP-M345; antitumor; mitosis; apoptosis