Author(s):
Hesham Sami, Rajesh Gour, Akhlesh Kumar Singhai
Email(s):
heshamsami1999@gmail.com
DOI:
10.52711/2231-5713.2024.00036
Address:
Hesham Sami*, Rajesh Gour, Akhlesh Kumar Singhai
School of Pharmacy, LNCT University, Kolar Road, Bhopal - 462042, Madhya Pradesh, India.
*Corresponding Author
Published In:
Volume - 14,
Issue - 3,
Year - 2024
ABSTRACT:
Geldanamycin (GA) bind heat-shock protein-90 (HSP-90) and destabilize its client proteins including v-Src, Bcr-Abl, RAF-1, Erb-B2, some growth factor receptors and steroid receptors. As a result, several oncoproteins are subjected to ubiquitination and proteasomal destruction by HSP-90 active compounds. HSP-90 active substances can either stop apoptosis from occurring or promote growth arrest, differentiation, and apoptosis depending on the cellular environment. Numerous preclinical models and clinical trials have demonstrated anticancer activity for a number of HSP-90 inhibitors. The well-known HSP-90 inhibitor geldanamycin’s clinical development was hampered by its hepatic toxicity. Geldanamycin at low doses can sensitize Bcr/Abl-expressing leukemia cells to death in the presence of inadequate doxorubicin concentrations by activating caspase. In another example, 17AAG in combination with taxol shows enhanced cytotoxic effects on taxol-resistant Erb-B2 overexpressing breast cancer cells. The benzoquinone ansamycin geldanamycin selectively binds to GRP94 and HSP-90 both in vivo and in vitro. When cells are treated with geldanamycin, HSP-90’s molecular chaperone function is changed. This prevents some cytosolic proteins from maturing, reduces their activity, and/or modifies their stability. On the other hand, nothing is known about GRP94’s function in protein folding or how geldanamycin affects this endoplasmic reticulum (ER) homologue of HSP-90. In this work, we show that geldanamycin is a strong inducer of the cellular stress response in the ER, leading to the transcriptional up-regulation of ER chaperones and production of the gadd153/CHOP transcription factor in a range of cell lines. Here we mention the anticancerous activity of HSP-90 (Heat Shock Protein 90) Inhibitor geldanamycin and some researches in field of anticancerous activity of Geldanamycin.
Cite this article:
Hesham Sami, Rajesh Gour, Akhlesh Kumar Singhai. A Short Review on Introduction and Researches on Anticancerous Activity of Geldanamycin. Asian Journal of Pharmacy and Technology. 2024; 14(3):220-4. doi: 10.52711/2231-5713.2024.00036
Cite(Electronic):
Hesham Sami, Rajesh Gour, Akhlesh Kumar Singhai. A Short Review on Introduction and Researches on Anticancerous Activity of Geldanamycin. Asian Journal of Pharmacy and Technology. 2024; 14(3):220-4. doi: 10.52711/2231-5713.2024.00036 Available on: https://ajptonline.com/AbstractView.aspx?PID=2024-14-3-5
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