Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells

Authors

  • Chaturvedi Vishal Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Jonnala Ujwal Kumar Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Cherukuvada Veera Brahmendra Swamy Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Rangaraj Nandini Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Gunda Srinivas Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Rathinam Kumaresan Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Singh Shashi Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
  • Amere Subbarao Sreedhar Centre for Cellular and Molecular Biology, Hyderabad 500 007, Uppal Road, India. *Present address: Bio-Core Research Laboratory, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.

DOI:

https://doi.org/10.33393/dti.2011.1370

Keywords:

Hsp90, 17AAG, mitochondria, tumor cells, ΔΨm

Abstract

Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity.

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Published

2011-06-07

How to Cite

1.
Vishal C, Kumar JU, Swamy CVB, Nandini R, Srinivas G, Kumaresan R, Shashi S, Sreedhar AS. Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells. dti [Internet]. 2011 Jun. 7 [cited 2021 Sep. 22];5(1). Available from: https://journals.aboutscience.eu/index.php/dti/article/view/1370

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Original Research Article

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