Chemotherapy and autophagy-mediated cell death in pancreatic cancer cells

Ropolo, Alejandro; Bagnes, Claudia; Molejon, Maria Inés; Ré, Andrea Lo; Boggio, Verónica; Gonzalez, Claudio; Vaccaro, María I.

doi:10.1016/j.pan.2011.11.003

Cited by 21 publications

(17 citation statements)

References 63 publications

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“…For example, inhibition of autophagy in a pancreatic tumour cell line by knockdown of Beclin 1 or pharmacological inhibition of PIK3C3 was found to enhance apoptosis following treatment with chemotherapeutic agents (Ropolo et al, 2012). However, inhibition of autophagy in these cells by knockdown of ATG5 resulted in decreased levels of apoptosis, suggesting that autophagy-independent apoptotic functions of ATG5 are at play in pancreatic cancer (Ropolo et al, 2012).…”

Section: Regulation Of Autophagy By Apoptosismentioning

confidence: 99%

Life in the balance – a mechanistic view of the crosstalk between autophagy and apoptosis

Rubinstein

Kimchi

2012

Journal of Cell Science

214

187

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SummaryCellular stress triggers a fascinating decision-making process in cells; they can either attempt to survive until the stress is resolved through the activation of cytoprotective pathways, such as autophagy, or can commit suicide by apoptosis in order to prevent further damage to surrounding healthy cells. Although autophagy and apoptosis constitute distinct cellular processes with often opposing outcomes, their signalling pathways are extensively interconnected through various mechanisms of crosstalk. The physiological relevance of the autophagy-apoptosis crosstalk is not well understood, but it is presumed to facilitate a controlled and well-balanced cellular response to a given stress signal. In this Commentary, we explore the various mechanisms by which autophagy and apoptosis regulate each other, and define general paradigms of crosstalk on the basis of mechanistic features. One paradigm relates to physical and functional interactions between pairs of specific apoptotic and autophagic proteins. In a second mechanistic paradigm, the apoptosis or autophagy processes (as opposed to individual proteins) regulate each other through induced caspase and autolysosomal activity, respectively. In a third paradigm unique to autophagy, caspases are recruited and activated on autophagosomal membranes. These mechanistic paradigms are discernible experimentally, and can therefore be used as a practical guide for the interpretation of experimental data.

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Section: Regulation Of Autophagy By Apoptosismentioning

confidence: 99%

Life in the balance – a mechanistic view of the crosstalk between autophagy and apoptosis

Rubinstein

Kimchi

2012

Journal of Cell Science

214

187

View full text Add to dashboard Cite

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“…It is the third manner of death besides necrosis and apoptosis [8–9]. The results of the study showed that compared with the I/R group, the IH+I/R group showed aggravated structural damage of neurons and a decreased survival density of neurons at each time point (6h and 24h) as well as enhanced expression of beclin1 protein detected by immunohistochemical staining and RT-PCR, which indicated that autophagy exists in the process of pure cerebral ischemia-reperfusion, and intermittent hypoxia can further activate autophagy and worsen neuron loss after cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

mTOR/autophagy pathway in the hippocampus of rats suffering intermittent hypoxia preconditioning and global cerebral ischemia-reperfusion

Zhao

Guo

et al. 2017

Oncotarget

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We explored the role of mTOR/autophagy pathway in the aggravation of cerebral ischemia-reperfusion nerve injury caused by intermittent hypoxia. Eighty male wistar rats were divided into four groups by the random number method: sham operation group (SO group, n=20), cerebral ischemia-reperfusion group (I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group (IH+I/R group, n=20), intermittent hypoxia and cerebral ischemia-reperfusion group plus mTOR inhibitor group (inhibitor group, n=20). The results showed that compared with the SO group, HE staining showed structural damage of neurons at each time point, the immunohistochemical assay showed an increasing number of mTOR and beclin1 immune-positive cells (P<0.05) and RT-PCR showed enhanced expression of mTOR and beclin1 protein in the I/R group (P<0.05). Compared with the I/R group, HE staining showed exacerbating structural damage of neurons at each time point, the immunohistochemical assay showed an increasing number of mTOR and beclin1 immune-positive cells (P<0.05) and RT-PCR showed enhanced expression of mTOR and beclin1 protein in the IH+I/R group (P<0.05). Compared with the IH+I/R group, HE staining showed remissive structural damage of neurons at each time point, the immunohistochemical assay showed a decreasing number of mTOR immune-positive cells and a rising number of beclin1immune-positive cells (P<0.05) and RT-PCR showed weakened expression of mTOR protein and enhanced expression of beclin1 protein in the inhibitor group (P<0.05). Thence, the present study indicated that intermittent hypoxia preconditioning can aggravate the nerve injury of the global cerebral ischemia-reperfusion model, and the mechanism is associated with the activation of mTOR/autophagy pathway.

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“…According to the research conducted by Ropolo et al [27], chemotherapy by way of administering an analogue of deoxycytidine-gemcitabine (pyrimidine antimetabolite), which is the current standard in the treatment of pancreatic cancer, induces autophagy in pancreatic cancer cells. The early induction of autophagy by gemcitabine leads to the death of cancer cells, and this process is mediated by the activation of the transmembrane protein, VMP1, that triggers autophagy in mammals.…”

Section: Discussionmentioning

confidence: 99%

Autophagy in the pancreatic islets after the administration of cladribine in accordance to two different modes of therapy

Jasinski

Lis-Sochocka

Chylińska-Wrzos

et al. 2017

Current Issues in Pharmacy and Medical Sciences

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The treatment of neoplastic and neurodegenerative diseases is still difficult. This because the cytostatic drugs have adverse effects on healthy organs. Among the drugs that have been investigated in the therapy of cancers and multiple sclerosis are the purine analogues. The aim of our study was the evaluation of the effect of cladribine on the process of autophagy in the healthy pancreas via two dosage models. The experiment was conducted on female Wistar rats which were placed within the experimental and control groups of two dosage models: model (A) -cladribine being administered in a daily dose of 0.1 mg/kg by weight for 7 days, and model (B) -cladribine being administered in a daily dose of 0.07 mg/kg by weight in 3 cycles of 6 days with 5 weeks break. A-bis and B-bis groups were included within, respectively, groups A and B. Here, decapitation occurred after 4 weeks break in drug administration. In our work, autophagy was investigated via the expression of the LC3B protein (Light Chain 3B protein). The comparison of the results of many independent trials was built upon the use of the Kruskal-Wallis non-parametric test. Significance was set at p < 0.005. In our results, average LC3B expression was observed in 100% of all cells in the group A, 70% in group B and 60% in group B-bis. We not observed average LC3B expression in the other groups. Moreover, a poor reaction was observed in 55% of all cells in group A-bis. We noted significant relationships between control group and group A, between the control group and group B, and between group A-bis and groups B and B-bis. These results demonstrate that cladribine has led to the induction of autophagy in the pancreatic islet cells.

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Chemotherapy and autophagy-mediated cell death in pancreatic cancer cells

Cited by 21 publications

References 63 publications

Life in the balance – a mechanistic view of the crosstalk between autophagy and apoptosis

Life in the balance – a mechanistic view of the crosstalk between autophagy and apoptosis

mTOR/autophagy pathway in the hippocampus of rats suffering intermittent hypoxia preconditioning and global cerebral ischemia-reperfusion

Autophagy in the pancreatic islets after the administration of cladribine in accordance to two different modes of therapy

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