Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer

Lü, Qing; Zhang, Purong; Zhang, Xin; Chen, Jie

doi:10.3892/ijmm_00000291

Cited by 53 publications

(46 citation statements)

References 16 publications

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“…The present study provides evidence for the first time that Tan IIA has an anticancer effect on human RCC. A number of studies have demonstrated that Tan IIA is able to reduce cell vitality due to its cytotoxic properties (14). The results of the MTT assay in our study also showed that treatment with Tan IIA resulted in a marked and dose-dependent inhibition of the growth of 786-O cells.…”

Section: Discussionsupporting

confidence: 64%

Tanshinone IIA arrests cell cycle and induces apoptosis in 786-O human renal cell carcinoma cells

Wei

Zhou²,

Hu³

et al. 2012

Oncology Letters

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Abstract. Tanshinone IIA (Tan IIA), isolated from the Chinese medicinal herb Danshen, has been reported to have anticancer effects in several tumor models, while its effects on renal cell carcinoma have not been studied. In the present study, we evaluated the effects of Tan IIA on growth inhibition and apoptosis in the renal cancer cell line 786-O and its mechanism of action. Results of the MTT assay indicated that the treatment of 786-O cells with Tan IIA resulted in a concentration-dependent decrease in cell viability. Flow cytometry analysis revealed that Tan IIA treatment caused apoptosis following cell cycle perturbation. Furthermore, we examined the expression of cell cycle and apoptosis-related proteins using immunoblotting, which indicated an upregulation of p53, p21, bax and caspase-3 in Tan IIA-treated cells compared with Tan IIA-untreated cells. These results suggest that the activation of p53 and the upregulation of its target genes, including p21 and bax, may be involved in the mitochondrial apoptosis induced by Tan IIA in 786-O cells.

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Section: Discussionsupporting

confidence: 64%

Tanshinone IIA arrests cell cycle and induces apoptosis in 786-O human renal cell carcinoma cells

Wei

Zhou²,

Hu³

et al. 2012

Oncology Letters

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“…This is in agreement with other reports (8,10,17,18). It is welldocumented that activation of ER stress activates the upstream element caspase 12, followed by the upregulation of the target protein C/EBP-homologous protein (CHOP; also known as GADD153) (24).…”

Section: The Effects Of Tan-iia On the Protein Expression Of Bax Bclsupporting

confidence: 83%

“…Breast cancer is the leading cause of cancerrelated death in women worldwide (16). Tan-IIA inhibition of human breast cancer cells is well-documented (8,(17)(18)(19). However, the molecular mechanisms are not understood clearly.…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression

et al. 2012

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Abstract. Breast cancer is the leading cause of cancer-related deaths in women worldwide. Tanshinone IIA (Tan-IIA) is one of the pure compounds from Salviae miltiorrhizae radix (Danshen). Tan-IIA can inhibit human breast cancer cells but the molecular mechanisms are not well understood. Our previous study showed that Tan-IIA can inhibit hep-J5 human hepatocellular carcinoma cells through the endoplasmic reticulum (ER) stress-induced apoptotic pathway. In the present study, we evaluated the effects of Tan-IIA on BT-20 human breast cancer cells and assessed the involvement of the ER-stress-apoptotic pathway. The cytotoxicity of Tan-IIA in BT-20 cells was measured by the MTT assay. The cell cycles were analyzed by flow cytometry. The expression of ER stress-related proteins in BT-20 cells treated with Tan-IIA were evaluated by western blotting and immunocytochemical staining. These results showed that Tan-IIA can inhibit BT-20 cells and increase the sub-G1 phase in a time-and dose-dependent manner. Tan-IIA could increase the protein expression of caspase 12, GADD153, caspase 3, phospho-JNK, phospho-p38 and Bax, but decreased Bcl-xl and phospho-ERK expression in BT-20 cells. These findings indicate that Tan-IIA possesses therapeutic potential for human breast cancer BT-20 cells; one of the molecular mechanisms may be through inducing ER stress and the MAPK pathway to induce apoptosis and inhibit proliferation.

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“…The cardiovascular and cerebrovascular efficacies of TSA were recognized early in the 1970s, and its sodium sulfonate derivative was marketed in China as a cardiovascular drug in the 1980s. More recently, various other pharmacological activities, including anti-inflammation (Ren et al, 2010), liver-and renal-protective effects (Zhang et al, 2009a), learning and memory improvement (Kim et al, 2009), and particularly its anticancer potential Lu et al, 2009;Shi et al, 2009;Zhang et al, 2009b), have been extensively studied and have attracted much attention from researchers worldwide. Previous reports strongly suggest that TSA is a promising leading compound for novel anticancer and cardiovascular drug development.…”

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confidence: 99%

Regioselective Glucuronidation of Tanshinone IIa after Quinone Reduction: Identification of Human UDP-Glucuronosyltransferases, Species Differences, and Interaction Potential

Wang¹,

Hao²,

Zhu³

et al. 2010

Drug Metabolism and Disposition

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ABSTRACT:We have previously identified that the predominant metabolic pathway for tanshinone IIa (TSA) in rat is the NAD(P)H:quinone oxidoreductase 1 (NQO1)-mediated quinone reduction and subsequent glucuronidation. The present study contributes to further research on its glucuronidation enzyme kinetics, the identification of human UDP-glucuronosyltransferase (UGT) isoforms, and the interaction potential with typical UGT substrates. A pair of regioisomers (M1 and M2) of reduced TSA glucuronides was found from human, rat, and mouse, whereas only M1 was found in dog liver S9 incubations. The overall glucuronidation clearance of TSA in human liver S9 was 11.8 ؎ 0.8 l/min/mg protein, 0.7-, 0.8-, and 3-fold of that in the mouse, rat, and dog, respectively. Using intrinsic clearance M2/M1 as a regioselective index, opposite regioselectivity was found between human (0.7) and mouse (1.3), whereas no significant regioselectivity was found in rat. In a sequential metabolism system, by applying human liver cytosol as an NQO1 donor combined with a screening panel of 12 recombinant human UGTs, multiple UGTs were found involved in the M1 formation, whereas only UGT1A9 and, to a very minor extent, UGT1A1 and UGT1A3 contributed to the M2 formation. Further enzyme kinetics, correlation, and chemical inhibition studies confirmed that UGT1A9 played a major role in both M1 and M2 formation. In addition, TSA presented a potent inhibitory effect on the glucuronidation of typical UGT1A9 substrates propofol and mycophenolic acid, with an IC 50 value of 8.4 ؎ 1.8 and 8.9 ؎ 1.9 M, respectively. This study will help to guide future studies on characterizing the NQO1-mediated reduction and subsequent glucuronidation of other quinones.Quinones are a large group of compounds ubiquitous in nature and characterized with great biological, pharmacological, and/or toxicological significance. Humans are unavoidably exposed to many endogenous quinones such as coenzyme Q, vitamin K, oxidized products of endogenous phenols, and some xenobiotic quinones from foods, environmental pollutants, and drugs. The carbonyl group in the quinone structure is often a determining functional factor for their activities (Oppermann, 2007). For example, the quinone/hydroquinone interconversion of coenzyme Q plays an important role in the electron transport involved in cellular respiration, and the one-electron and/or two-electron reduction of the quinone carbonyl group-triggered redox cycle also largely explains the pharmacological or toxicological activities of many quinones. Note that the quinone carbonyl reduction and subsequent conjugation constitute the major biotransformation and metabolic elimination pathway of most quinones. Therefore, the biotransformation study of quinones is essential for understanding their bioactivation, detoxification, and/or inactivation process.Tanshinones are a class of diterpene phenanthrenequinone compounds isolated from the dried root of Salvia miltiorrhiza (Fam. Labiatae), which is a widely used traditional Chinese medicine with w...

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Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer

Cited by 53 publications

References 16 publications

Tanshinone IIA arrests cell cycle and induces apoptosis in 786-O human renal cell carcinoma cells

Tanshinone IIA arrests cell cycle and induces apoptosis in 786-O human renal cell carcinoma cells

Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression

Regioselective Glucuronidation of Tanshinone IIa after Quinone Reduction: Identification of Human UDP-Glucuronosyltransferases, Species Differences, and Interaction Potential

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