Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel

Fonseca, Joana; Marques, Sandra; Silva, Patrícia; Brandão, Pedro; Cidade, Honorina; Pinto, Madalena; Bousbaa, Hassan

doi:10.3390/molecules21080982

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…The results obtained showed that BP-M345 has no effect on the inhibition of the p53-MDM2 interaction [ 33 ]. Thus, 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, such as podophyllotoxin, combretastatin A4, and colchicine [ 38 ], as well as some chalcones previously reported as potent antimitotic agents by our group [ 38 , 39 , 40 ], it was hypothesized that this diarylpentanoid could also act as antimitotic agent.…”

Section: Introductionmentioning

confidence: 99%

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

et al. 2021

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Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

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Section: Introductionmentioning

confidence: 99%

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

et al. 2021

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“…Also, other prenylated chalcones (e.g. O-prenyl derivative of 2′-hydroxy-3,4,4′,5,6′-pentamethoxychalcone) in combination with common anticancer drug, such as paclitaxel, have been shown to further inhibit cell growth, as determined with cell viability and proliferation assays (Fonseca et al, 2016).…”

Section: Results and Discusionmentioning

confidence: 99%

The influence of a single and double biotinylation of xanthohumol on its anticancer activity

2019

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Two biotinylated derivatives of the main hop chalcone xanthohumol (1) were prepared by a one-step synthesis via esterification using biotin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC×HCl) and 4-dimethylaminopyridine (DMAP) as coupling reagents. The products were characterized spectroscopically and their antiproliferative activity toward MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1 and Balb/3T3 cell lines was investigated using the SRB assay. For all three tested compounds the best activity was noted in the case of human (MCF-7) and mice (4T1) breast cancer cell lines (IC50 values < 9 μM). Both biotinylated derivatives showed slightly higher anticancer activity than xanthohumol (1) towards all types of tested breast cancer cells. Double biotinylated xanthohumol (3) proved to be the most active in inhibiting cell growth, with IC50 values equal to 5.35 ± 1.5 μM for 4T1 and 8.03 ± 0.53 µM for MCF-7 cell lines. Compound 3 was also more active than 1 and 2 against liver cancer cells HepG2 (IC50 = 17.37 ± 5.1 μM), while the IC50 values for 1 and 2 were equal to 21.5 ± 2.7 and 22.1 ± 3.9 µM, respectively. 4‑O‑biotinylxanthohumol (2) was the second most active growth inhibitor, particularly with respect to MCF-7 (IC50 = 6.19 ± 1.7 μM) and 4T1 (IC50 = 6.64 ± 0.4 μM) cell lines. Our preliminary study on biotinylated xanthohumol (1) have shown that this type of functionalization is an effective method for the production of active biomolecules and study on this area should be continued thereby extending their applications.

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“…Different cell death mechanisms induced by these molecules have already been described, such as apoptosis mediated by caspases [ 21 , 23 ], autophagy [ 21 ], methuosis [ 24 ], and unfolded protein response mediated cell death [ 25 ]. We already reported several chalcones with promising growth inhibitory activity in human cancer cell lines [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Among these, chalcones 1 – 3 ( Figure 1 ) revealed antiproliferative activity in A375-C5 (melanoma), MCF-7 (breast adenocarcinoma), and NCI-H460 (non-small cell lung cancer) cells [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

A New Chalcone Derivative with Promising Antiproliferative and Anti-Invasion Activities in Glioblastoma Cells

et al. 2021

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Glioblastoma (GBM) is the most common and most deadly primary malignant brain tumor. Current therapies are not effective, the average survival of GBM patients after diagnosis being limited to few months. Therefore, the discovery of new treatments for this highly aggressive brain cancer is urgently needed. Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, three chalcone derivatives were tested regarding their inhibitory activity and selectivity towards GBM cell lines (human and mouse) and a non-cancerous mouse brain cell line. The chalcone 1 showed the most potent and selective cytotoxic effects in the GBM cell lines, being further investigated regarding its ability to reduce critical hallmark features of GBM and to induce apoptosis and cell cycle arrest. This derivative showed to successfully reduce the invasion and proliferation capacity of tumor cells, both key targets for cancer treatment. Moreover, to overcome potential systemic side effects and its poor water solubility, this compound was encapsulated into liposomes. Therapeutic concentrations were incorporated retaining the potent in vitro growth inhibitory effect of the selected compound. In conclusion, our results demonstrated that this new formulation can be a promising starting point for the discovery of new and more effective drug treatments for GBM.

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Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel

Cited by 14 publications

References 34 publications

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

The influence of a single and double biotinylation of xanthohumol on its anticancer activity

A New Chalcone Derivative with Promising Antiproliferative and Anti-Invasion Activities in Glioblastoma Cells

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