SNX-2112 Induces Apoptosis and Autophagy of Nara-H Cells

Natsuko Fukuoka1, Osamu Nakamura2, Yoshiki Yamagami1

  • 1Department of Orthopaedic Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan.

Anticancer Research
|September 9, 2018
PubMed
Abstract

Insights

The heat shock protein 90 (Hsp90) inhibitor SNX-2112 effectively reduced Nara-H cell growth. SNX-2112 triggered apoptosis and autophagy by inhibiting mTOR and MAPK pathways, supporting its potential for treating soft tissue sarcomas.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Selective heat shock protein 90 (Hsp90) inhibitor SNX-2112 demonstrates antitumor properties across various cancer types.
  • This study specifically investigates the antitumor effects of SNX-2112 on Nara-H cells.

Purpose of the Study:

  • To evaluate the antitumor activity of SNX-2112 in Nara-H cells.
  • To elucidate the molecular mechanisms underlying SNX-2112's action, including its impact on autophagy and apoptosis signaling pathways.

Main Methods:

  • Cell proliferation assays were employed to assess the direct impact of SNX-2112 on Nara-H cell growth.
  • Western blotting and morphological analyses were utilized to examine the effects of SNX-2112 on key signaling pathways, including autophagy, apoptosis, mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK).

Main Results:

  • SNX-2112 significantly inhibited the proliferation of Nara-H cells.
  • Western blot analysis confirmed that SNX-2112 induced apoptosis and autophagy, concurrently inhibiting mTOR phosphorylation and suppressing the MAPK signaling pathway.
  • Morphological examinations corroborated the induction of autophagy and apoptosis by SNX-2112.

Conclusions:

  • SNX-2112 effectively induces autophagy and apoptosis in Nara-H cells through the inhibition of mTOR and MAPK signaling pathways.
  • These findings suggest that SNX-2112 holds promise as a therapeutic agent for human soft tissue sarcomas.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
15.1K
Autophagy01:27

Autophagy

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.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.9K
Induced Pluripotent Stem Cells01:13

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.1K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
5.6K
Adult Stem Cells01:33

Adult Stem Cells

Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
33.9K
Induced-fit Model01:13

Induced-fit Model

Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
89.4K