Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells

Lee, Jun Hyuk; Kang, Gyung Hwa; Kim, Kyung Chul; Kim, Kyoung Mi; Park, Dong Il; Choi, Byung Tae; Kang, Ho Sung; Lee, Yong Tae; Choi, Yung Hyun

doi:10.3892/ijo.21.6.1239

Cited by 76 publications

(78 citation statements)

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“…Baic- alin and baicalein are flavonoids derived from the root of Scutellaria baicalensis Georgi (Figure 1). It has been reported that baicalein, which has the same backbone structure as baicalin, shows a stronger cardioprotective effect and can inhibit the proliferation of cancer cells via induction of apoptosis [8][9][10][11]. A recent study showed that baicalin pretreatment reduced the hyperthermia, intracranial hypertension, and increase of nitric oxide metabolite levels during heatstroke; baicalin also suppressed the heatstroke-induced increase in IL-1β and TNF-α levels [12].…”

Section: Introductionmentioning

confidence: 99%

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

et al. 2010

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The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC proliferation, accompanied with the reduction of proliferating cell nuclear antigen (PCNA) expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF receptor β (PDGFRβ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFRβ-ERK1/2 signaling cascade.

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Section: Introductionmentioning

confidence: 99%

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

et al. 2010

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“…Several studies recently have shown that tetrandrine possesses antitumor activity in cultured tumor cells and animal models (19 -27). Tetrandrine induces G 1 -phase arrest in cells containing wild-type p53 (20,25) and apoptosis in p53 wild-type and null cells (20,22,25). However, the molecular mechanisms by which tetrandrine induces G 1 -phase arrest remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Tetrandrine Induces Early G1 Arrest in Human Colon Carcinoma Cells by Down-Regulating the Activity and Inducing the Degradation of G1-S–Specific Cyclin-Dependent Kinases and by Inducing p53 and p21Cip1

et al. 2004

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Tetrandrine is an antitumor alkaloid isolated from the root of Stephania tetrandra. We find that micromolar concentrations of tetrandrine irreversibly inhibit the proliferation of human colon carcinoma cells in MTT and clonogenic assays by arresting cells in G 1 . Tetrandrine induces G 1 arrest before the restriction point in nocodazole-and serum-starved synchronized HT29 cells, without affecting the G 1 -S transition in aphidicolin-synchronized cells. Tetrandrine-induced G 1 arrest is followed by apoptosis as shown by fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated nick end labeling, and annexin V staining assays. Tetrandrine-induced early G 1 arrest is mediated by at least three different mechanisms. First, tetrandrine inhibits purified cyclin-dependent kinase 2 (CDK2)/cyclin E and CDK4 without affecting significantly CDK2/cyclin A, CDK1/cyclin B, and CDK6. Second, tetrandrine induces the proteasome-dependent degradation of CDK4, CDK6, cyclin D1, and E2F1. Third, tetrandrine increases the expression of p53 and p21Cip1 in wild-type p53 HCT116 cells. Collectively, these results show that tetrandrine arrests cells in G 1 by convergent mechanisms, including down-regulation of E2F1 and up-regulation of p53/p21Cip1 .

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“…12 Moreover, it is reported that tetrandrine led to G1 blockade and induced apoptosis in many cancer cells, such as HL60, A549 and U937, [13][14][15] through synergistic inhibition of ERK. 16 These studies suggest that tetrandrine could be a promising agent for the treatment of cancer. However, its anticarcinogenic effects on HCC and the molecular mechanism of its anticarcinogenesis have not been well studied yet, although it has been evaluated for the treatment of cancer for some time.…”

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confidence: 99%

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

Liu¹,

Gong²,

Mao³

et al. 2011

Intl Journal of Cancer

130

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Tetrandrine, a bisbenzylisoquinoline alkaloid component of broadly used traditional Chinese medicine, has antitumor effects against some cancers. In our study, we investigated the effects of tetrandrine on the human hepatocellular carcinoma (HCC) in vitro and in vivo. The results showed that tetrandrine effectively induced apoptosis of liver cancer cell in a dose-and time-dependent manner accompanied by alteration of cell morphology, chromatin fragmentation and caspase activation. Tetrandrine treatment also induced intracellular accumulation of reactive oxygen species (ROS), and ROS scavengers (LNAC and GSH) completely blocked the effects of tetrandrine-induced apoptosis, suggesting that the generation of ROS plays an important role in tetrandrine-induced apoptosis. Although the activities of JNK and ERK were inhibited significantly by tetrandrine treatment, JNK and ERK are not involved in the tetrandrine-induced apoptosis. In contrast, Akt activity was found to be closely related to tetrandrine-induced apoptosis. The data demonstrated that Akt activity inhibitor LY294002 synergistically promoted tetrandrine-induced apoptosis of HCC, whereas ectopic expression of Akt contrastly abrogated partial of the tetrandrine-induced apoptosis. These data suggest that Akt signal is the downstream event of ROS generation in the tetrandrine-induced HCC cell apoptosis. Moreover, the results of xenograft in nude mice were consistent with that of the in vitro studies. Therefore, our data suggest that tetrandrine may be a promising agent for the treatment of HCC as a regulator of ROS/Akt pathway.

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Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells

Cited by 76 publications

References 0 publications

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

Baicalin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation through suppressing PDGFRβ-ERK signaling and increase in p27 accumulation and prevents injury-induced neointimal hyperplasia

Tetrandrine Induces Early G1 Arrest in Human Colon Carcinoma Cells by Down-Regulating the Activity and Inducing the Degradation of G1-S–Specific Cyclin-Dependent Kinases and by Inducing p53 and p21Cip1

Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma

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