Next Article in Journal
A Review of Key Biological and Molecular Events Underpinning Transformation of Melanocytes to Primary and Metastatic Melanoma
Previous Article in Journal
Magnetic Silica-Coated Iron Oxide Nanochains as Photothermal Agents, Disrupting the Extracellular Matrix, and Eradicating Cancer Cells
Open AccessArticle

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

1
Department of Pharmacy, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
2
Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
3
Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
4
Centro nazionale per il controllo e la valutazione dei farmaci, Istituto Superiore di Sanità, 00161 Rome, Italy
5
WHO Collaborating Centre for the Epidemiology, Detection and Control of Cystic and Alveolar Echinococcosis (in Animals and Humans), Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
6
European Union Reference Laboratory for Parasites, Istituto Superiore di Sanità (ISS), 00161 Rome, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(12), 2042; https://doi.org/10.3390/cancers11122042
Received: 26 November 2019 / Revised: 9 December 2019 / Accepted: 14 December 2019 / Published: 17 December 2019
Pancreatic cancer (PC) is one of the most lethal, chemoresistant malignancies and it is of paramount importance to find more effective therapeutic agents. Repurposing of non-anticancer drugs may expand the repertoire of effective molecules. Studies on repurposing of benzimidazole-based anthelmintics in PC and on their interaction with agents approved for PC therapy are lacking. We analyzed the effects of four Food and Drug Administration (FDA)-approved benzimidazoles on AsPC-1 and Capan-2 pancreatic cancer cell line viability. Notably, parbendazole was the most potent benzimidazole affecting PC cell viability, with half maximal inhibitory concentration (IC50) values in the nanomolar range. The drug markedly inhibited proliferation, clonogenicity and migration of PC cell lines through mechanisms involving alteration of microtubule organization and formation of irregular mitotic spindles. Moreover, parbendazole interfered with cell cycle progression promoting G2/M arrest, followed by the emergence of enlarged, polyploid cells. These abnormalities, suggesting a mitotic catastrophe, culminated in PC cell apoptosis, are also associated with DNA damage in PC cell lines. Remarkably, combinations of parbendazole with gemcitabine, a drug employed as first-line treatment in PC, synergistically decreased PC cell viability. In conclusion, this is the first study providing evidence that parbendazole as a single agent, or in combination with gemcitabine, is a repurposing candidate in the currently dismal PC therapy. View Full-Text
Keywords: drug repurposing; synergism; combined treatments; pancreatic ductal adenocarcinoma; mitotic catastrophe; benzimidazoles drug repurposing; synergism; combined treatments; pancreatic ductal adenocarcinoma; mitotic catastrophe; benzimidazoles
Show Figures

Figure 1

MDPI and ACS Style

Florio, R.; Veschi, S.; di Giacomo, V.; Pagotto, S.; Carradori, S.; Verginelli, F.; Cirilli, R.; Casulli, A.; Grassadonia, A.; Tinari, N.; Cataldi, A.; Amoroso, R.; Cama, A.; De Lellis, L. The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer. Cancers 2019, 11, 2042.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop