Cationic lipid-conjugated hydrocortisone as selective antitumor agent.

Abstract

Hydrocortisone, the endogenously expressed steroidal, hormonal ligand for glucocorticoid receptor (GR), is body's natural anti-inflammatory and xenobiotic metabolizing agent. It has both palliative as well as adverse effects in different cancer patients. Herein, we show that conjugation product of C16-carbon chain-associated cationic lipid and hydrocortisone (namely, HYC16) induces selective toxicity in cancer (e.g. melanoma, breast cancer and lung adenocarcinoma) cells with least toxicity in normal cells, through induction of apoptosis and cell cycle arrest at G2/M phase. Further, significant tumor growth inhibition was observed in syngeneic melanoma tumor model with considerable induction of apoptosis in tumor-associated cells. In contrast to hydrocortisone, significantly higher anti-angiogenic behavior of HYC16 helped in effective tumor shrinkage. This is the first demonstration to convert natural hormone hydrocortisone into a selective bioactive entity possessing anti-tumor effect.

• Authors: Bhowmira Rathore, Madhan Mohan Chandra Sekhar Jaggarapu, Anirban Ganguly, Hari Krishna Reddy Rachamalla, Rajkumar Banerjee
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 108 Pg. 309-321 (Jan 27 2016) ISSN: 1768-3254 [Electronic] France
• PMID: 26695732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cations
• Lipids
• Hydrocortisone

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cations (chemistry, pharmacology)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Hydrocortisone (chemical synthesis, chemistry, pharmacology)
• Lipids (chemistry, pharmacology)
• Molecular Structure
• Structure-Activity Relationship