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
. 2010 Jun;24(6):2126-34.
doi: 10.1096/fj.09-148999. Epub 2010 Feb 4.

Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cells

Sonia Rana  1 , Kalpana Gupta, Jose Gomez, Shigemi Matsuyama, Amitabha Chakrabarti, Munna L Agarwal, Anju Agarwal, Mukesh K Agarwal, David N Wald
Affiliations

Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cells

Sonia Rana et al. FASEB J. 2010 Jun.

Abstract

The identification of agents that preferentially kill cancer cells while protecting normal cells offers the potential to overcome toxicities found in many existing chemotherapeutic agents. Because p53 is frequently inactivated in cancer, agents that preferentially kill p53-null cells and protect wild-type p53-expressing cells are highly desirable chemotherapeutic agents. By using pairs of isogenic colon cancer cell lines that differ only in p53 expression (RKO and HCT116), securinine was found to exhibit these properties. Securinine (30 microM) induces apoptosis in 73% of p53-null HCT116 cells (LD(50) 17.5 microM) as opposed to 17.6% of HCT116 parental cells (LD(50) 50 microM) at 72 h after treatment. The mechanism of securinine-mediated death in p53-deficient cells involves the induction of the p53 family member, p73. Interestingly, the proapoptotic protein p73 is down-regulated in colon cancer cells expressing p53. This differential regulation of p73 in a p53-dependent fashion reveals a novel pathway for preferentially targeting cancer cells. In contrast to p53-deficient cells, cells expressing p53 are protected from cell death through the p53-mediated up-regulation of p21. These studies reveal a novel approach to specifically target colon cancer cells lacking p53 as well as identify a novel clinically relevant pathway to selectively induce p73 in p53-null cells.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms

LinkOut - more resources