title: Temsirolimus induced structural transition of cancerous renal cystatin to normal form in rats: In vitro mechanistic approach underlying renal cancer prevention.
abstract: Globally, renal cell carcinomas (RCCs) represent a major portion of patients suffering from cancer. Temsirolimus is an anti-renal cancer drug that has already been approved in poor-risk metastatic RCC (mRCC) patients. In our present study, we have evaluated the in vitro effect of varying concentrations of temsirolimus on cancerous rat kidney cystatin; renal cancer was induced in rats making use of dimethylnitrosamine (DMN). It has already been reported that cancerous rat kidney cystatin performs its activity in an efficacious manner as compared to normal rat kidney cystatin, so here an attempt was made to see the effect of temsirolimus on this increased activity of cystatin in renal cancers. Anti-papain activity assay was utilized to see this effect and it was found that temsirolimus reduces the increased activity of cancerous rat kidney cystatin similar to that of normal rat kidney cystatin. Further, to have an insight into temsirolimus induced structural alterations in cancerous rat kidney cystatin; various spectroscopic assays viz. UV, Fluorescence, Circular dichroism (CD) and FTIR spectroscopy were employed. UV and Fluorescence spectroscopy shows cancerous rat kidney cystatin transformation to normal form in the presence of temsirolimus. FTIR and CD spectroscopy confirmed the complete structural reversion of cancerous rat kidney cystatin to normal form in the presence of 40μM temsirolimus. Thus, it can said that temsirolimus causes renal cystatin to revert to normal form; the increased activity of renal cystatin observed in incidences of renal cancer is restored back to normal thereby halting the progression of renal cancer.
authors.affiliation: Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh 202 002, India.
authors.forename: Anas
authors.initials: A
authors.lastname: Shamsi
authors.affiliation: Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh 202 002, India.
authors.forename: Azaj
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, Faculty of Life Science, Aligarh Muslim University, Aligarh 202 002, India. Electronic address: bbbano17@gmail.com.
authors.forename: Bilqees
authors.initials: B
authors.lastname: Bano
mesh_terms: D000818:Animals; D015891:Cystatins / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D010206:Papain / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D015891:Cystatins; C401859:temsirolimus; D010206:Papain; D020123:Sirolimus
keywords: CD spectroscopy; Cancerous rat kidney cystatin; Dimethylnitrosamine; Normal rat kidney cystatin; Renal cancer; Temsirolimus