JOURNAL ARTICLE

Embelin suppresses STAT3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase PTEN

Ji Young Heo, Hyun Jung Kim, Sung-Moo Kim, Kyung-Ran Park, Sang-Yoon Park, Seong Won Kim, Dongwoo Nam, Hyeung-Jin Jang, Seok-Geun Lee, Kyoo Seok Ahn, Sung-Hoon Kim, Bum Sang Shim, Seung-Hoon Choi, Kwang Seok Ahn
Cancer Letters 2011 September 1, 308 (1): 71-80
21565443
Even though embelin, an inhibitor of the XIAP, is known to exhibit anti-inflammatory and anti-cancer activities, very little is known about its mechanism of action. Here, we investigated whether embelin mediates its effect through interference with the signal transducer and activator of transcription 3 (STAT3) pathway. We found that embelin inhibited constitutive STAT3 activation in a variety of human cancer cell lines such as U266, DU-145, and SCC4 cells. The suppression of STAT3 was mediated through inhibition of the activation of JAK2 and c-Src. Pervanadate treatment also reversed the embelin-induced down-regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that embelin-induced the expression of the tyrosine phosphatase PTEN and deletion of the PTEN gene by small interfering RNA abolished the ability of embelin to inhibit STAT3 activation. Besides, embelin failed to suppress STAT3 activation in PTEN-null PC3 cells, thus indicating that the inhibitory effect of embelin on STAT3 is PTEN-dependent. Embelin down-regulated the expression of STAT3-regulated gene products; this correlated with the suppression of cell proliferation and invasion, and the induction of apoptosis through the activation of caspase-3. Overall, our results indicate that the anti-inflammatory and anti-cancer activities previously assigned to embelin may be mediated in part through the suppression of the STAT3 pathway.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21565443
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"