Skip Navigation
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.


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.

Your Environment. Your Health.

Publication Detail

Title: Anti-cancer effects of JKA97 are associated with its induction of cell apoptosis via a Bax-dependent and p53-independent pathway.

Authors: Luo, Wenjing; Liu, Jinyi; Li, Jingxia; Zhang, Dongyun; Liu, Mingchao; Addo, James K; Patil, Shivaputra; Zhang, Lin; Yu, Jian; Buolamwini, John K; Chen, Jingyuan; Huang, Chuanshu

Published In J Biol Chem, (2008 Mar 28)

Abstract: p53, one of the most commonly mutated genes in human cancers, is thought to be associated with cancer development. Hence, screening and identifying natural or synthetic compounds with anti-cancer activity via p53-independent pathway is one of the most challenging tasks for scientists in this field. Compound JKA97 (methoxy-1-styryl-9H-pyrid-[3,4-b]-indole) is a small molecule synthetic anti-cancer agent, with unknown mechanism(s). In this study we have demonstrated that the anti-cancer activity of JKA97 is associated with apoptotic induction via p53-independent mechanisms. We found that co-incubation of human colon cancer HCT116 cells with JKA97 inhibited HCT116 cell anchorage-independent growth in vitro and tumorigenicity in nude mice and also induced a cell apoptotic response, both in the cell culture model and in a tumorigenesis nude mouse model. Further studies showed that JKA97-induced apoptosis was dramatically impaired in Bax knock-out (Bax(-/-)) HCT116 cells, whereas the knock-out of p53 or PUMA did not show any inhibitory effects. The p53-independent apoptotic induction by JKA97 was confirmed in other colon cancer and hepatocarcinoma cell lines. In addition, our results showed an induction of Bax translocation and cytochrome c release from the mitochondria to the cytosol in HCT116 cells, demonstrating that the compound induces apoptosis through a Bax-initiated mitochondria-dependent pathway. These studies provide a molecular basis for the therapeutic application of JKA97 against human cancers with p53 mutations.

PubMed ID: 18218619 Exiting the NIEHS site

MeSH Terms: Animals; Apoptosis Regulatory Proteins/genetics; Apoptosis Regulatory Proteins/metabolism; Apoptosis/drug effects*; Body Weight/drug effects; Carbolines/chemistry; Carbolines/pharmacology*; Cell Line, Tumor; Female; Humans; Mice; Mice, Nude; Molecular Structure; Neoplasms/genetics; Neoplasms/metabolism*; Neoplasms/pathology*; Protein Transport; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Styrenes/chemistry; Styrenes/pharmacology*; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; Xenograft Model Antitumor Assays; bcl-2-Associated X Protein/genetics; bcl-2-Associated X Protein/metabolism*

to Top