Molecular Mechanism of Tanshinone against Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common malignant tumor of the male urinary system in Europe and America. According to the data in the World Cancer Report 2020, the incidence rate of PCa ranks second in the prevalence of male malignant tumors and varies worldwide between regions and population groups. Although early PCa can achieve good therapeutic results after surgical treatment, due to advanced PCa, it can adapt and tolerate androgen castration-related drugs through a variety of mechanisms. For this reason, it is often difficult to achieve effective therapeutic results in the treatment of advanced PCa. Tanshinone is a new fat-soluble phenanthraquinone compound derived from Salvia miltiorrhiza that can play a therapeutic role in different cancers, including PCa. Several studies have shown that Tanshinone can target various molecular pathways of PCa, including the signal transducer and activator of transcription 3 (STAT3) pathway, androgen receptor (AR) pathway, phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, and mitogen-activated protein kinase (MAPK) pathway, which will affect the release of pro-inflammatory cytokines and affect cell proliferation, apoptosis, tumor metabolism, genomic stability, and tumor drug resistance. Thus, the occurrence and development of PCa cells are inhibited. In this review, we summarized the in vivo and in vitro evidence of Tanshinone against prostate cancer and discussed the effect of Tanshinone on nuclear factor kappa-B (NF-κB), AR, and mTOR. At the same time, we conducted a network pharmacology analysis on the four main components of Tanshinone to further screen the possible targets of Tanshinone against prostate cancer and provide ideas for future research.

Keywords: Apoptosis; NF-κB; Tanshinone; mTOR; prostate cancer.

Figure 1

Chemical structures of four Tanshinone monomers.

Figure 2

Effect of Tanshinone on prostate cancer. induced by Tanshinone are noted by using →, while the inhibition represented by ⊣ symbol.

Figure 3

Effect of Tanshinone on mTOR. induced by Tanshinone are noted by using →, while the inhibition represented by ⊣ symbol.

Figure 4

Venny of four components of Tanshinone ((a): Tanshinone I and Prostate Cancer; (b): Tanshinone IIA and Prostate Cancer; (c): Dihydrotanshinone I and Prostate Cancer; (d): Cryptotanshinone and Prostate Cancer).

Figure 5

Protein network analysis of four Tanshinone components ((a): Tanshinone Ir; (b): Tanshinone IIA; (c): Dihydrotanshinone I; (d): Cryptotanshinone).

Figure 6

Go enrichment analysis of four components of Tanshinone((a): Tanshinone Ir; (b): Tanshinone IIA; (c): Dihydrotanshinone I; (d): Cryptotanshinone).

Figure 7

KEGG enrichment analysis of four components of Tanshinone ((a): Tanshinone Ir; (b): Tanshinone IIA; (c): Dihydrotanshinone I; (d): Cryptotanshinone).