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.

Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug

“…Among them, the cell tumor antigen p53 (TP53), myc proto-oncogene protein (myc), transcription factor AP-1 (JUN), Proto-oncogene tyrosine-protein kinase SRC(SRC), caspase-3 (CASP3), and epidermal growth factor receptor(EGFR) play a key role in the anti-HCC process of TsIIA. In addition, previous studies have confirmed that TsIIA, as a fat-soluble polyphenol, can enter cells directly through the cell membrane due to its fat-soluble property and rely on the direct combination of the D ring in the molecular structure of TsIIA with the groove in the DNA molecule, thus interfering with the synthesis and transcription of DNA and thus exerting the anti-tumor effect ( 53 ). This is consistent with our results.…”

“…Interestingly, TsIIA has significant antioxidant activity. From the structure of TsIIA, the antioxidant effect of TsIIA mainly depends on the D-ring (furan or dihydrofuran), and the structural change of the D-ring will also affect the antioxidant capacity ( 53 ). Secondly, TsIIA can also significantly increase the expression and activity of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST).…”

“…Previous studies have confirmed that the overproduction of ROS in cells can not only directly lose DNA molecules and induce the occurrence and progression of tumors, but also significantly promote the metabolic reorganization of tumors and activate intracellular pathways related to tumor occurrence and progression. However, TsIIA can stabilize DNA molecules, down-regulate the activity of some pathways, and change the metabolic reorganization of tumor cells by inhibiting the level of ROS in cells and increasing antioxidant activity ( 53 , 151 , 152 ). Secondly, we have discussed the antioxidant activity of TsIIA in the section on liver protection in this article.…”

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival

“…23 Modern pharmacological studies have shown that all of the aforementioned components have reduced chemotherapy side effects and enhanced immunity. 24,25 Despite the outstanding clinical effectiveness of CLG, its mechanism of action must continue to be investigated. Therefore, the role of the PI3K/Akt/mTOR signaling pathway in the effect of CLG on CRC in nude mice was investigated in this study.…”

“…Other components comprise cryptotanshinone (0.55 mg/mL), diosgenin (0.58 mg/mL), 9‐Oxo‐10(E),12(E)‐octadecadienoic acid (0.18 mg/mL), adenosine (0.56 mg/mL), and emodin (0.39 mg/mL) 23 . Modern pharmacological studies have shown that all of the aforementioned components have reduced chemotherapy side effects and enhanced immunity 24,25 . Despite the outstanding clinical effectiveness of CLG, its mechanism of action must continue to be investigated.…”