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Effects of octreotide on autophagy markers and cell viability markers related to metabolic activity in rat pituitary tumor cells

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Abstract

Purpose

The aim of this work was to investigate possible direct effects of the somatostatin analog octreotide on autophagy markers and markers of cellular metabolic activity using in vitro cultured rat pituitary tumor cells (GH3 cell line).

Methods

We measured two markers of the autophagic flux in cell lysates by Western blot and MTT reductive activity, total cellular ATP levels, pyruvate dehydrogenase (PDH) complex activity in cells lysates as markers of cell viability related to metabolic activity.

Results

Octreotide (100 nM) treatment induced autophagy activation (increased LC3-I protein lipidation) and enhanced the autophagic flux (SQSTM1/p62 protein downregulation) in GH3 cells in different incubation media, in detail in Hank’s balanced salt solution (HBSS) as well as in maintenance medium with serum. We did not observe any decrease of redox activity and energy production related to the induction of autophagy by octreotide. On the other hand, short-term treatments with octreotide in HBSS tended to enhance MTT reduction activity and to increase PDH complex enzymatic activity and ATP levels measured in GH3 cell lysates.

Conclusions

We provided evidence that octreotide can affect autophagy in pituitary tumor cells. The observed effects of octreotide were not related to a decrease of cellular metabolic activity. Finally, the induction of autophagy was either short-lived or overshadowed by other factors in the long term and this limit does not help clarifying their real impact on the pharmacological activity of somatostatin analogs.

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Funding

This study was supported by local funds (2012–2013) from the University of Brescia to G.T. and by a grant from Novartis Farma Spa (Origgio, Italy) (G.T.). Funding sources have not had any role in study design and interpretation of data.

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Authors and Affiliations

  1. Unit of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123, Brescia, Italy

    Giovanni Tulipano

  2. Division of Endocrinology, IRCCS San Raffaele Hospital, San Raffaele Vita- Salute University – Head, Milan, Italy

    Andrea Giustina

Authors
  1. Giovanni Tulipano
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  2. Andrea Giustina
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Corresponding author

Correspondence to Giovanni Tulipano.

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Conflict of interest

G.T. and A.G. have received research grants from Novartis Farma Spa. A.G. has received consulting and lecture fees from Ipsen, Novartis and Pfeizer.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Tulipano, G., Giustina, A. Effects of octreotide on autophagy markers and cell viability markers related to metabolic activity in rat pituitary tumor cells. Pituitary 23, 223–231 (2020). https://doi.org/10.1007/s11102-020-01028-0

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  • DOI: https://doi.org/10.1007/s11102-020-01028-0

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