Effect of Supplementation of Tanshinone IIA and Sodium Tanshinone IIA Sulfonate on the Anticancer Effect of Epirubicin: An In Vitro Study

Szu-Erh Chan,Su-Yu Chien,Hui-Yi Lin,Dar-Ren Chen,Chin-Cheng Su,Hung-Wen Lai,Shou-Jen Kuo

doi:10.1155/2011/841564

Abstract

Tanshinone IIA (Tan IIA) and sodium tanshinone IIA sulfonate (STS) were found to have protective effects on cardiomyocyte against adriamycin-induced damage and may be used clinically. It is unclear whether the supplementation of STS or Tan IIA would affect the anticancer activity of anthracycline. To evaluate the effect of Tan IIA or STS on the anticancer of epirubicin, the cell viability, apoptosis, Akt expression, and uptake of epirubicin after supplementation of Tan IIA or STS in the epirubicin-treated BT-20 cells were measured and compared. Tan IIA inhibited BT-20 cell growth and induced apoptosis in a time- and dose-dependent manner. When Tan IIA was used with epirubicin, an increase of BT-20 cells apoptosis was accompanied by the decreasing phosphorylation of Akt. STS had no effect on the cell viability of BT-20 cells. However, when used with epirubicin, STS decreased the epirubicin-induced cytotoxicity and apoptosis in BT-20 cells. The antagonistic effect of STS on epirubicin-induced cytotoxicity in BT-20 cells occurred concomitantly with the reduced epirubicin uptake and the increased phosphorylation of Akt. STS decreased the uptake of epirubicin in BT-20 cells and blocked epirubicin-induced apoptosis through activation of Akt.

Highlights

Breast cancer is one of the leading causes of cancer death among women all over the world; it accounts for approximately 30% of all new cancer cases each year, with an annual incidence of approximately 200,000 in the United States [1]
When Tanshinone IIA (Tan IIA) was used with epirubicin, an increase of BT-20 cells apoptosis was accompanied by the decreasing phosphorylation of Akt
Our study was designed to test the effect of supplementation of sodium tanshinone IIA sulfonate (STS) or Tan IIA on the anticancer effect of epirubicin in an in vitro BT-20 cell line model

Summary

Introduction

Breast cancer is one of the leading causes of cancer death among women all over the world; it accounts for approximately 30% of all new cancer cases each year, with an annual incidence of approximately 200,000 in the United States [1]. In Taiwan, the incidence of breast cancer has increased steadily from 10/105 in 1979 to 50/105 in 2006, and it is the most commonly occurring cancer and leading cause of death among Taiwanese women [2] Anthracyclines such as doxorubicin and epirubicin are highly efficacious against breast cancer [3], and are commonly used in adjuvant or neoadjuvant chemotherapy to reduce local recurrence or distant metastasis [4, 5]. For a cardioprotective agent to be used clinically, it is important to confirm that it will not impair the anticancer effect of chemotherapy [28] At present, it is unclear whether the supplementation of STS or Tan IIA would affect the anticancer effect of anthracyclines, such as epirubicin. The objective of this in vitro study was to elucidate the influence of STS or Tan IIA on the epirubicin-induced cytotoxicity of breast cancer cells

Materials and Methods

Results

Discussion