New publication: Autophagosome accumulation-mediated ATP energy deprivation induced by penfluridol triggers nonapoptotic cell death of lung cancer via activating unfolded protein response

Nanolive is happy to announce a new publication on the Official journal of the Cell Death Differentiation Association by our customers at the Taipei Medical University in Taiwan[1].

Non-small-cell lung cancers (NSCLCs) are the most common type of lung cancer. Traditional therapies work by inducing apoptosis in cancer cells. However, modifications in cancer cells, such as mutations in intrinsic apoptotic signaling pathways, lead to chemotherapy resistance.

An alternative way to induce cell death and retard tumor growth in apoptosis-resistant cancers is to target the autophagic pathways. Given the problem that natural compounds known for inducing autophagy have a low oral bioavailability, a solution would be to repurpose autophagic in-use drugs so that they work as therapy for a wider variety of clinical conditions. Penfluridol, a drug used in schizophrenia treatment, has proved to be a repurposed drug for breast, pancreas and brain tumors. Nevertheless, its effects in NSCLCs had not yet been studied.

Hung and colleagues studied the effects of penfluridol in human NSCLC A549 and HCC827 cells lines. Samples of both cell lines after penfluridol treatment were analyzed by immunohistochemistry, flow cytometry and immunofluorescence assays. The 3D Cell Explorer was used to observe the changes of apoptotic features in A549 and HCC827 cell lines treated with penfluridol (Figure 1).

The results showed that, at a non-toxic concentration, penfluridol suppressed motility of NSCLC cells. Cell death due to phagosome formation was observed both in vivo and in vitro in cells treated with penfluridol. Autophagosomes were mainly the result of adenosine triphosphate (ATP) energy deprivation, and the ER stress-induced p38-mediated unfolded protein response pathway seemed to be the mechanism involved in the process. The authors concluded that penfluridol-induced autophagy may be a promising NSCLC treatment.

Read the full publication here

Figure 1. Evaluation of the formation of apoptotic bodies (red arrows) in A549 and HCC827 cells treated with penfluridol (7.5 μM) for 24h under the 3D Cell Explorer (image from W.-Y. Hung et al., “Autophagosome accumulation-mediated ATP energy deprivation induced by penfluridol triggers nonapoptotic cell death of lung cancer via activating unfolded protein response,” Cell Death Dis., vol. 10, no. 8, p. 538, Aug. 2019)

 

[1]         W.-Y. Hung et al., “Autophagosome accumulation-mediated ATP energy deprivation induced by penfluridol triggers nonapoptotic cell death of lung cancer via activating unfolded protein response,” Cell Death Dis., vol. 10, no. 8, p. 538, Aug. 2019.

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