Cationic lipid-conjugated hydrocortisone as selective antitumor agent

• DOI: 10.1016/j.ejmech.2015.11.033
• Publication Date: 2015-11-24T11:20:19Z
• Authors: Bhowmira Rathore; Madhan Mohan Chan...; Anirban Ganguly; Hari Krishna Redd...; Rajkumar Banerjee
• Keywords: 0301 basic medicine; 0303 health sciences; Dose-Response Relationship, Drug; Hydrocortisone; Molecular Structure; Cell Cycle; Antineoplastic Agents; Apoptosis; Lipids; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Cations; Drug Screening Assays, Antitumor; Cell Proliferation

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.