title: 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.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: Bhowmira
authors.initials: B
authors.lastname: Rathore
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), 2, Rafi Marg, New Delhi 110 001, India.
authors.forename: Madhan Mohan
authors.initials: MM
authors.lastname: Chandra Sekhar Jaggarapu
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), 2, Rafi Marg, New Delhi 110 001, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), 2, Rafi Marg, New Delhi 110 001, India.
authors.forename: Hari Krishna
authors.initials: HK
authors.lastname: Reddy Rachamalla
authors.affiliation: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), 2, Rafi Marg, New Delhi 110 001, India. Electronic address: banerjee@iict.res.in.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006854:Hydrocortisone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D008055:Lipids; D006854:Hydrocortisone
keywords: Cationic lipid; Glucocorticoid receptor; Hydrocortisone; Tumor