Tanshinone I effectively induces apoptosis in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells

Abstract

Abstract. Danshen (Salvia miltiorrhiza Bunge) is a herb that has been widely and successfully used for treating inflammatory diseases in clinics in Asia. The relatively abundant tanshinones, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone, have been isolated from Danshen. These tanshinones are the major diterpenes isolated from Danshen, and show cytotoxic effects on cell lines derived from human carcinomas of the colon, ovary, lung, mouth, and breast. Recently, anti-cancer activities of tanshinone IIA have been reported, which suggest that the structurally similar tanshinone I may possess similar cytotoxic effects on tumor cells. We investigated the effect of tanshinone I on the induction of apoptosis in human breast cancer cells (MCF-7 and MDA-MB-231) in vitro. Tanshinone I inhibited cell proliferation of MCF-7 and MDA-MB-231 cells in a doseand time-dependent manner, as assayed by MTT. In addition, TUNEL assay and flow cytometry showed that tanshinone I significantly induced apoptosis in MCF-7 and MDA-MB-231 cells. The induction of apoptotic cell death was mediated by the activation of caspase 3, the downregulation of the level of the anti-apoptotic protein, Bcl-2, and the upregulation of the level of the pro-apoptotic protein, Bax. Taken together, these results reveal a potential mechanism for the anti-cancer effect of tanshinone I on human breast cancer cells, and suggest that tanshinone I may serve as an effective adjunctive reagent in the treatment of human breast cancer.

Oxidative stress and breast cancer biomarkers: the case of the cytochrome P450 2E1

“…[48] Given that CYP2E1 gene expression is under the transcriptional control of factors responsive to inflammation [19,29,49,50] it was theorized that inhibition of glycolysis in breast cancer cells bearing diverse genetic background would lead to alternative CYP2E1 cellular levels and hence dissimilar ROS. [42] On the other side inhibition of glycolysis would lead to increased ROS generation [31] that could be altered by CYP2E1 enzymatic activity.…”

Possible role of Pax-6 in promoting breast cancer cell proliferation and tumorigenesis

“…Based on the levels of ER and drug sensitivity status, breast cancers falls into two broad categories, ER-positive or ER-negative types (18). ER is expressed in about 60% of all breast cancers, which generally possess better prognosis and is often responsive to anti-estrogen therapy.…”

MCF-7 breast carcinoma cells do not express caspase-3

“…Curiously, several reports still claim the presence of caspase-3 in the breast carcinoma cell line MCF-7 in which this enzyme is supposed to contribute to apoptosis signaling [7][8][9][10][11][12][13][14][15]. This was not only demonstrated indirectly via fluorometric assay systems measuring caspase-3-like activities-that might be also elicited by the closely related caspase-7-but by Western blotting analyses demonstrating directly the presence of this protease in MCF-7 cells.…”

“…In addition, it was shown that caspase-3 is the primary activator of apoptotic (low molecular) DNA fragmentation via cleavage-mediated inhibition of ICAD [22]. Thus, it is puzzling that caspase-3-deficient MCF-7 cells exhibit DNA fragmentation and other apoptotic characteristics following cell death induction as described [7][8][9][10][11][12][13][14][15]. While it is still possible that caspase-3-deficient MCF-7 cells display high molecular weight DNA fragmentation that might be occasionally mistaken for the typical apoptotic DNA fragmentation, the detection of a caspase-3 protein in MCF-7 cells [7,8,11,[13][14][15] with a partially deleted CASP-3 gene is cause for concern.…”