Cryptotanshinone inhibits human glioma cell proliferation by suppressing STAT3 signaling.

Abstract

Malignant gliomas (MGs) are among the most aggressive types of cancers in the human brain. Frequent tumor recurrence caused by a lack of effective therapeutic approaches results in a poor prognosis. Signal transducer and activator of transcription 3 (STAT3), an oncogenic protein, is constitutively activated in MGs and predicts a poor clinical outcome. STAT3 therefore is considered to be a promising target for the treatment of MGs. Cryptotanshinone (CTS), the main bioactive compound from the root of Salvia miltiorrhiza Bunge, has been reported to have various pharmacological effects. However, little is known about its function in MG cells. In this study, we evaluated the effect of CTS on the proliferation of human glioma cell lines (T98G and U87). Our results revealed that CTS significantly suppresses glioma cell proliferation. The phosphorylation of STAT3 Tyr705, but not Ser727, was inhibited by CTS, and STAT3 nuclear translocation was attenuated. Overexpression of constitutively active mutant STAT3C reversed the inhibitory effect of CTS, while knockdown STAT3 showed a similar inhibitory effect as CTS treatment. Following the downregulation of STAT3-regulated proteins cyclinD1 and survivin, cell cycle progression significantly arrested in G1/G0 phase. These results indicate that CTS may be a potential antiproliferation agent for the treatment of MGs and that its mechanism may be related to the inhibition of STAT3 signaling.

• Authors: Liang Lu, Cuixian Li, Dong Li, Ying Wang, Chun Zhou, Weiwei Shao, Jin Peng, Yan You, Xinwen Zhang, Xiaoyan Shen
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 381 Issue 1-2 Pg. 273-82 (Sep 2013) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 23740516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mutant Proteins
• Phenanthrenes
• RNA, Small Interfering
• STAT3 Transcription Factor
• STAT3 protein, human
• Phosphotyrosine
• cryptotanshinone

Topics

• Animals
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• G1 Phase (drug effects)
• Glioma (drug therapy, metabolism, pathology)
• Humans
• Mutant Proteins (metabolism)
• Phenanthrenes (pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Phosphotyrosine (metabolism)
• RNA, Small Interfering (metabolism)
• Rats
• S Phase (drug effects)
• STAT3 Transcription Factor
• Signal Transduction (drug effects)