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Tetrandrine



RESEARCH



Tetrandrine
Objective To investigate the effect of tetrandrine on the ultrastructure of scar fibroblasts. Methods The cells were cultured in DMEM containing 80ug/ml tetrandrine for 24h and the uhrastructure of the cells was observed under TEM. Results The fibroblasts became smaller with smaller nuclei and unclear nucleoli, and the organellae also became smaller and much less after tetrandrine treatment. Conclusion Tetrandrine has the effect on the uhrastructure, so it may inhibit cellular proliferation and collagen synthesis.
--He XiaoSheng;Zhong XiaoChunHe XiaoSheng;Zhong XiaoChun. Effect of tetrandrine on the ultrastructure of scar fibroblasts. Zhe Jiang Yi Xue. 2005; 27 (9): 665-666.

Objective To investigate the regulation effect of tetrandrine on fibroblast’s apoptosis.Methods The experimental samples were divided into five groups, including blank control, ethanol control and positive control groups according to concentration gradient (0.5, 1.0, 2.0 mg/L).Fibroblast’s apoptosis index was detected by flow cytometry and DNA ladder was investigated by UV light after electrophoresis. Results T2 group was found typical apoptopic peak after treatment by 2.0 mg/L tetrandrine for 48 h and its apoptosis index rose with concentration and treatment time of tetrandrine.Its DNA after electrophoresis was found in UV light 200 bp and euploid pieces.But apoptosis index of blank control was zero.Conclusion Tetrandrine can induce apoptosis of fibroblast in quality concentration and time dependence.
--Fu Hongyi, Cao Zhidong, Li Hui, Wang Xiaoling. Effect of Tetrandrine on Fibroblast’s Apoptosis of Scar. Zhong Guo Yao Ye. 2010; 19 (11): 8-9.


Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs) In Vitro
Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs). Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), we found that the IC50 for inhibition of proliferation is 15.3 ± 4.1 μM for SUM-149 and 24.3 ± 2.1 μM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC50 around 1 μM for SUM-149 and around 2 μM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH) positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs.
More and more evidence suggests that TICs sustain cancer growth and cause tumor metastasis and recurrence after therapies. From a clinical point of view, therapies targeting TICs may have the potential to cure the cancer because they target the root of tumor. However, more and more evidence shows that TICs are more resistant than non-TICs to multiple cancer therapies including chemotherapy and radiation. Tetrandrine can target breast cancer TICs in vitro by the mammosphere formation assay and ALDH assay. Further in vivo and mechanistic studies assays are needed to fully determine the significance of this finding. Nevertheless, tetrandrine has been used for treatment of hypertension and inflammation in China for thousands of years. Recently, tetrandrine has been tried in clinic to treat refractory and relapsed acute myelogenous leukemia in China.
Wei Xu, Bisrat G. Debeb, Lara Lacerda, Jessica Li and Wendy A. Woodward. Cancers 2011, 3, 2274-2285; doi:10.3390/cancers3022274

Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia
The potential mechanism of the chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from acute myeloid leukemia. In a multicenter clinical trial, 38 patients with poor risk forms of AML were treated with tetrandrine (TET), a potent inhibitor of the MDR-1 efflux pump, combined with daunorubicin (DNR), etoposide and cytarabine (TET–DEC). Overall, postchemotherapy marrow hypoplasia was achieved in 36 patients. Sixteen patients (42%) achieved complete remission or restored chronic phase, 9 achieved partial remission (PR) and 13 failed therapy. Toxicities included infection, myelosuppression, stomatitis, mucositis, cerebellar toxicity and reversible cardiotoxicity. There was no significant difference in response for P-gp-positive and -negative patients. P-gp function was assessed in 26 patients by flow cytometric analysis, TET-contained plasma-augmented DNR accumulation relative to pretreatment plasma in K562/A02 cells by a median value of 88±101% (range, 11–501%). However, there was no difference in DNR uptake between responding and non-responding patients. Our data showed that TET–DEC was relatively well tolerated in these patients with poor risk AML, and had encouraging antileukemic effects.
Leukemia Research. Volume 30, Issue 4 , Pages 407-413, April 2006.



 
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