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J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 21 of 27

28. Spiperone, an antipsychotic, induces colorectal carcinoma cell death by a calcium-
mediated apoptosis

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Annamaria Antona , Konkonika Roy , Beatrice Riva , Suresh Velnati , Marco Varalda , Gianluca
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Baldanzi , Armando Genazzani , Daniela Capello 1
1 Dept Traslational Medicine, Università del Piemonte Orientale, Novara 28100, Italy.
2 Dept Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, Italy.
3 Center for translational research on Allergic and Autoimmune Diseases (CAAD), Novara 28100, Italy.
Colorectal cancer (CRC), one the most common malignancies, with increasing incidence and mortality
rate worldwide, requires novel therapeutic strategies for its treatment. As developing new drugs is a time-
and cost-intensive process with unexpected side effects, drug repositioning provides an effective strategy for
accelerating drug development. Some antipsychotics currently used in human therapy reported potential
anti-tumoral activity, thus in this study we intended to investigate their activity against CRC and CRC-stem
cells (CRC-SCs).

We screened a panel of commercially available psychotropic drugs for their antitumoral activity on HCT116
cell line. Regardless for their receptor specificity, the viability data showed that this cell line was sensitive
to just some drugs, especially spiperone, with an IC of 4 µmol/L. Spiperone was also highly toxic for CRC-
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SCs, inducing cell death by both apoptosis and necrosis with an IC < 6 µmol/L. To verify its mechanism
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2+
of action, we investigated the role of spiperone on Ca homeostasis in HCT116 by using the Fura-2 probe.
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We observed that it increases cytoplasmic Ca in CRC cells in a dose dependent manner. Experiments
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performed in the absence of extracellular Ca demonstrated that spiperone increased cytoplasmic Ca
originating from endoplasmic reticulum (ER); this was further confirmed by the induction of ER depletion
with 2,5-tBHQ (specific SERCA inhibitor) followed by spiperone treatment resulted in an accentuated store
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operated Ca entry response. Restoration of extracellular Ca in the presence of spiperone further increased
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cytoplasmic Ca , suggesting that this drug is also active on plasma membrane Ca channels.
Concluding, our data suggest that the anti-tumoral activity of spiperone might be due to Ca movements
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through ER and plasma membrane channels. Further experiments are needed to better clarify the
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mechanism of action of spiperone in Ca signalling and its possible repurposing as an antineoplastic drug.
29. Circulating tumor cells in patients with non small cell lung cancer: pilot study, initial results

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Roberta Carbone , Sara Parini , Marzia De Marni , Silvia Restelli , Paolo Aretini , Francesca
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Lessi , Chiara Maria Mazzanti , Renzo Luciano Boldorini , Elena Trisolini , Ciro Isidoro ,
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Caterina Casadio 2
1 Tethis S.p.A. Via Russoli, 3, Milan 20143, Italy.
2 Thoracic Surgery department, Università del Piemonte Orientale, Novara 28100, Italy.
3 Fondazione Pisana Per la Scienza, S. Giuliano Terme, Pisa 56017, Italy.
4 SCDU Pathology department, Università del Piemonte Orientale, Novara 28100, Italy.
5 Department of Health Sciences, Università del Piemonte Orientale, Novara 28100, Italy.
Introduction: Lung cancer is the main cause of cancer mortality worldwide and the number of new cases
is still rising. Early detection might be paramount to diagnose curable stages. There is growing interest
about isolation of circulating tumor cells (CTC). This pilot study aimed at isolating epithelial putative CTCs
in peripheral blood of early stage lung cancer patients using Smart BioSurface CTC assay, a nanoparticle-