Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules

Abstract

The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 small interfering RNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anticancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.

Cryptotanshinone inhibits breast cancer cell growth by suppressing estrogen receptor signaling

“…Recently, CPT was reported to inhibit the androgen receptor activity and suppress prostate cancer growth in androgen-dependent manner, but the reason for that is not due to the direct bind to androgen receptor and is attributed to its functional inhibition of LSD1-mediated demethylation of H3K9. 19,20 Thanshinone I has been reported to induce apoptosis of breast cancer cells, 27 so it is possible that Thanshinone I also could inhibit ER transcriptional activity due to the similarity of the chemical structures of Thanshinone I and CPT. However, we found that anshinones I less effectively inhibited E2-induced transcriptional activity and expression of the ER target gene (pS2, and Cat D) in the presence of E2, compared with CPT, which is consistent with the same inhibitory effect of anshinones I on ERpositive as well as ER-negative cancer cells.…”

Tanshinone I induces human colorectal cancer cell apoptosis: The potential roles of Aurora A-p53 and survivin-mediated signaling pathways

“…Since T1 exhibited inhibitory effects on breast and lung cancer (27)(28)(29), we sought to treat human colorectal cancer cell lines as well as normal colon epithelial cells with T1. After 72 h of T1 treatment at various concentrations, HCT116 colorectal cell with wild-type p53 protein displayed decreased viability in a dose-dependent manner.…”

“…Recently, the anticancer effect of T1 has been discovered in prostate, breast and lung cancers (27,28). Moreover, T1 was revealed to greatly inhibit Aurora A expression at both gene and protein levels (11).…”

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“…The study revealed a potential anticancer effect of tanshinone-I on breast cancer cells, suggesting that tanshinone-I may serve as an effective drug for the treatment of breast cancer 116 . Tanshinone II-A, isolated from Salvia miltiorrhiza, induced apoptosis which was linked to proteolytic cleavage of a major component in apoptotic cell death mechanism 117 .…”