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.

Effects of Salvia miltiorrhiza on CNS Neuronal Injury and Degeneration: A Plausible Complementary Role of Tanshinones and Depsides

“…In the successive decades, the number of pharmacological and clinical studies grew rapidly proving not only cardiovascular properties but widespread activities in several pathologies. Many interesting, promising therapeutic applications of S. miltiorrhiza extracts or single constituents have now appeared in the literature and include acute ischemic stroke [8,9], AD [10][11][12], osteoporosis [13], atherosclerosis [14], fulminant hepatic failure [15], and malignant gliomas [16]. In virtue of having few side effects, S. miltiorrhiza and its single constituents have been widely and successfully used in clinics in China, Korea, Japan, and other Asian countries for the treatment of heart and cerebrovascular disease, hepatitis, hepatocirrhosis, neuroasthenic insomnia, cancer, chronic renal failure, and dysmenorrhea [1,2,4].…”

MicroRNA-122-3p inhibits tumor cell proliferation and induces apoptosis by targeting Forkhead box O in A549 cells

“…Cell viability was then analyzed by adding 20 µl 10 mg/ml MTT (Sigma-Aldrich) to 0.2 ml culture medium and incubated for 3 h at 37˚C. Following removal of the medium, formazan (in dimethylsulfoxide) was added, and the 590 nm optical density was recorded using a Multiskan EX (Thermo Fisher Scientific, Inc.) (20).…”

Salvia miltiorrhizacompounds protect the liver from acute injury by regulation of p38 and NFκB signaling in Kupffer cells

“…Recent findings for S. miltiorrhiza components indicate that cryptotanshinone inhibits human glioma cell proliferation (Lu et al, 2013), salvianolic acid A can be used to treat Alzheimer's disease (Cao et al, 2013), and tanshinone I and tanshinone IIA protect the liver from acute and chronic injury (Park et al, 2009). However, although more than 20 active components have been isolated from S. miltiorrhiza, the molecules with liver-protective effects are unclear.…”