Anticancer Effect of Tanshinones on Female Breast Cancer and Gynecological Cancer

Abstract

Female breast cancer, ovarian cancer, cervical cancer, and endometrial cancer are the most common tumors and the most common causes of cancer-related mortality worldwide in women. Drugs derived from natural plants play important roles in malignant tumor therapy. Salvia miltiorrhiza is a commonly used Chinese herb which has been used in the treatment of liver diseases and cardiovascular diseases because of its positive effect of promoting blood circulation, increasing oxidative stress, and removing blood stasis. Recently, studies have found that fat-soluble components of Salvia miltiorrhiza such as tanshinone II, tanshinone I, cryptotanshinone, and dihydrotanshinone I displayed good antitumor activity in vivo and in vitro for gynecological cancer by different molecular mechanisms. In this study, the latest research progress on the antitumor effect and mechanism of tanshinone compounds in breast cancer and gynecological cancer was reviewed to provide references for the research and clinical application of these compounds (tanshinone II, tanshinone I, cryptotanshinone, and dihydrotanshinone I).

Keywords: female breast cancer; gynecological cancer; molecular mechanism; tanshinones; traditional Chinese medicine.

FIGURE 1

Main fat-soluble components in Salvia miltiorrhiza (Tanshinone IIA, cryptotanshinone, tanshinone I, and dihydrotanshinone I).

FIGURE 2

Molecular mechanism of tanshinones inhibiting cell proliferation. Tanshinones inhibit cancer cell proliferation by inducing cell apoptosis and cell cycle arrest. c-PARP, pro-apoptosis–related proteins (cleaved PARP; caspase-3, cysteine aspastic acid–specific protease 3; Bax, Bcl2-associated X protein; Bcl-2, B-cell lymphoma-2; Bcl-xl, Bcl2-associated Xl protein; CDK4, cyclin-dependent kinase 4).

FIGURE 3

Molecular mechanism of tanshinones inhibiting cell migration, invasion, metastasis, and EMT. Tanshinones inhibit protein expression in migration, invasion, metastasis, and EMT. FAK, focal adhesion kinase; MMPs, matrix metalloproteinases; ICAM-1, intercellular cell adhesion molecule-1; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; YAP, Yes1 associated transcriptional regulator.

FIGURE 4

Molecular mechanism of tanshinones increasing the efficacy of chemotherapy and radiotherapy. Tanshinones inhibit protein expression of P-gp, BCRP, MRP1, ABCG2, Tau, and β-catenin. P-gp, P-glycoprotein; multidrug resistance-associated protein 1; ABCG2, ATP binding cassette subfamily G member 2; Tau, microtubule-associated protein; β-catenin, beta-cadherin–associated protein.

FIGURE 5

Molecular mechanism of tanshinones inhibiting angiogenesis. Tanshinones inhibit protein expression of VEGF, COX2, and HIF-1α. VEGF, vascular endothelial growth factor; COX2, cytochrome C oxidase II; HIF-1α, hypoxia-inducible factor 1 subunit alpha.