Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Jan;22(1):145-53.
doi: 10.1007/s12253-015-9988-6. Epub 2015 Oct 6.

Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of Cisplatin with Simultaneous Reduction in its Nephrotoxictiy

Affiliations
Free article

Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of Cisplatin with Simultaneous Reduction in its Nephrotoxictiy

Vinayak Sudhir Jamdade et al. Pathol Oncol Res. 2016 Jan.
Free article

Abstract

Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as chemotherapeutic agent. However, it remains as most widely employed anticancer agent to treat various solid tumours like head-neck, testicular, ovarian and mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as well as anti-cancer agent. The present study was carried out to explore the effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its anti-tumour activity in 7, 12 dimethyl benz [a] anthracene induced mammary tumour in animal model. Renal damage was accessed by measuring serum level of creatinine, blood urea nitrogen and albumin whereas systemic inflammation was accessed by measuring level of pro-inflammatory cytokines like tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) and nuclear factor kappa B (NFκB). Moreover, assessment of tumour reduction was done by measuring tumour volume and percentage tumour reduction. A single dose of cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood urea nitrogen, NF-kB, TNF-α and IL-6 levels along with decrease in albumin and IL-10 levels. However, there were no significant changes in raloxifene (8 mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked decrease in serum creatinine, blood urea nitrogen, TNF-α and IL-6 levels whereas increase in albumin and IL-10 levels. However, pre-treatment of raloxifene showed maximum tumour reduction as compared to cisplatin and raloxifene treated groups. The present study demonstrates that raloxifene potentiates anti-tumour activity of cisplatin with simultaneous reduction in its nephrotoxicity, and this effect is attributed to its direct anti-inflammatory activity.

Keywords: Cisplatin; Inflammation; Nephrotoxicity; Pro-inflammatory cytokines; Raloxifene.

PubMed Disclaimer

References

    1. Nat Rev Cancer. 2007 Aug;7(8):573-84 - PubMed
    1. Kidney Int. 2001 Dec;60(6):2118-28 - PubMed
    1. Cancer Lett. 2004 Jul 8;210(1):35-40 - PubMed
    1. Anticancer Agents Med Chem. 2015;15(5):647-56 - PubMed
    1. J Carcinog. 2006 May 15;5:15 - PubMed

Publication types

MeSH terms