Gene interactions and pathways from curated databases and text-mining
Apoptosis 2008, PMID: 19002588

Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation.

Oh, Jung Hwa; Lee, Tae-Jin; Kim, Sang Hyun; Choi, Yung Hyun; Lee, Sang Han; Lee, Jin Man; Kim, Young-Ho; Park, Jong-Wook; Kwon, Taeg Kyu

Withaferin A, a major chemical constituent of Withania somnifera, has been reported for its tumor cell growth inhibitory activity, antitumor effects, and impairing metastasis and angiogenesis. The mechanism by which withaferin A initiates apoptosis remains poorly understood. In the present report, we investigated the effect of withaferin A on the apoptotic pathway in U937 human promonocytic cells. We show that withaferin A induces apoptosis in association with the activation of caspase-3. JNK and Akt signal pathways play crucial roles in withaferin A-induced apoptosis in U937 cells. Furthermore, we have shown that overexpression of Bcl-2 and active Akt (myr-Akt) in U937 cells inhibited the induction of apoptosis, activation of caspase-3, and PLC-gamma1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappaB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells.

Diseases/Pathways annotated by Medline MESH: Leukemia
Document information provided by NCBI PubMed

Text Mining Data

NF-kappaB ⊣ Akt: " Furthermore, we have shown that overexpression of Bcl-2 and active Akt ( myr-Akt ) in U937 cells inhibited the induction of apoptosis, activation of caspase-3, and PLC-gamma1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappaB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells "

caspase-3 → Akt: " Furthermore, we have shown that overexpression of Bcl-2 and active Akt ( myr-Akt ) in U937 cells inhibited the induction of apoptosis, activation of caspase-3 , and PLC-gamma1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappaB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells "

caspase-3 → Bcl-2: " Furthermore, we have shown that overexpression of Bcl-2 and active Akt ( myr-Akt ) in U937 cells inhibited the induction of apoptosis, activation of caspase-3 , and PLC-gamma1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappaB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells "

PLC-gamma1 → caspase-3: " Furthermore, we have shown that overexpression of Bcl-2 and active Akt ( myr-Akt ) in U937 cells inhibited the induction of apoptosis, activation of caspase-3 , and PLC-gamma1 cleavage by withaferin A. Taken together, our results indicated that the JNK and Akt pathways and inhibition of NF-kappaB activity were key regulators of apoptosis in response to withaferin A in human leukemia U937 cells "

Manually curated Databases

No curated data.