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Related Concept Videos

Autophagy01:27

Autophagy

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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
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Autophagic Cell Death01:18

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Related Experiment Video

Updated: Oct 3, 2025

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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Repurposing autophagy regulators in brain tumors.

Edgar Petrosyan1,2, Jawad Fares1,2, Alex Cordero1,2

  • 1Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

International Journal of Cancer
|February 18, 2022
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Certain antidepressants can effectively treat brain tumors by influencing autophagy, a key cellular process. This research reviews FDA-approved antidepressants with anticancer effects, offering new therapeutic avenues for brain cancer patients.

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Area of Science:

  • Neuro-oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Malignant brain tumors like glioblastoma multiforme (GBM) and brain metastases present significant treatment challenges due to the blood-brain barrier (BBB).
  • The BBB restricts the efficacy of many conventional cancer therapeutics.
  • Repurposing existing medications that cross the BBB and possess anticancer properties is a promising strategy.

Purpose of the Study:

  • To review FDA-approved antidepressants with demonstrated cytotoxic effects against tumor cells.
  • To investigate the role of autophagy modulation as a mechanism for the antitumor activity of these antidepressants.
  • To identify specific antidepressants that induce or inhibit autophagy in various cancer models.

Main Methods:

  • Comprehensive literature review of studies reporting on FDA-approved antidepressants and their effects on cancer cells.
  • Analysis of research focusing on the involvement of autophagy in mediating the anticancer effects of antidepressants.
  • Categorization of antidepressants based on their observed impact on autophagy (induction or inhibition).

Main Results:

  • Several FDA-approved antidepressants exhibit cytotoxicity against diverse tumor models, including brain tumors.
  • Autophagy dysregulation is a central mechanism underlying the antitumor effects of these antidepressants.
  • Specific antidepressants like imipramine, maprotiline, fluoxetine, and escitalopram were identified as autophagy inducers, while others like nortriptyline, clomipramine, and paroxetine were inhibitors. Sertraline and desipramine showed context-dependent effects.

Conclusions:

  • FDA-approved antidepressants represent a viable class of drugs for repositioning in cancer therapy, particularly for brain tumors.
  • Modulation of autophagy by antidepressants is a key factor in their observed anticancer efficacy.
  • Further research into these BBB-permeable agents could lead to novel therapeutic strategies for central nervous system malignancies.