*3.1. Tanshinone and NF-κB*

NF-κB is a multipotent transcription factor responsible for regulating cell signaling and various biological processes, such as immune response, inflammation, cell transformation, cell proliferation, angiogenesis, cancer invasion, and metastasis [98]. This factor can be activated by a variety of signals, including growth factors, protein kinases, oxidative stress inducers, mitogens, pro-inflammatory cytokines, and chemokines (TNF-, Il-1, Il-8, Il-6, CXCL12), and environmental stress factors [98,99]. In addition, NF-κB has been proven to be significantly related to the occurrence and progression of PCa. During the development of PCa, NF-κB can promote the survival, invasion, angiogenesis, metastasis, and chemical resistance of cancer cells by inducing pro-survival genes (such as bcl-2 and bcl-xl), proinflammatory cytokines, and vascular growth factors [100,101]. Second, IκB kinase -α (IKKα) and IκB kinase -β (IKKβ) signaling molecules upstream of the NF-κB signaling pathway can directly affect AR activity via phosphorylation and induce the expression of the constitutive active AR splicing form (AR-v7), which is one of the key factors in PCa castration resistance and drug resistance [102,103]. Interestingly, available laboratory data have long shown that Tanshinone inhibits cancer cell growth and progression by inhibiting the overactivation of NF-κB in cancer cells [104,105], although this has not yet been demonstrated in PCa cells. Tanshinone has been shown to inhibit the secretion of NFκB activating factors such as interleukins, vascular cell adhesion molecule-1 (VCMM-1), and intercellular adhesion molecule-1 (ICAM-1) as well as monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF-α). It can also directly inhibit the phosphorylation of upstream molecules by IB kinase-IKK and IKK and simultaneously induce degradation of IKK and IKK. It can also inhibit the NF-κB pathway by decreasing the expression levels of toll-like receptor (TLR), myeloid differentiation factor 88 (MyD88), transferrin 6 (TRF6), and other proteins involved in the NF-κB signaling pathway and directly inhibiting the activation and expression of NF-κB [106–108]. It is noteworthy that Tanshinone can inhibit the activity of COX2 and play a significant inhibitory role in the transcription and expression of COX2 by acting similarly to non-steroidal anti-inflammatory drugs [108–110], while the prostaglandins generated by COX2-mediated production not only have a direct nourishing effect on PCa cells [111]. It also acts as an effective activator of NF-κB

Inflammation is essential for the occurrence and development of all kinds of cancers, including prostate cancer. The signal pathway most closely associated with the inflammatory response is NF-κB. It not only promotes the onset and progression of prostate cancer but also has a clear crosstalk relationship with androgen receptor signals. In fact, it has crosstalk with most signal molecules in the cell. Therefore, based on the current laboratory data, targeting NF-κB is probably a promising treatment [112]. Tanshinone can inhibit the occurrence and progression of prostate cancer by virtue of its excellent ability to regulate inflammation and NF-κB. Unfortunately, current studies have not confirmed the effects of Tanshinone on inflammatory cytokines and the NF-κB pathway in prostate cancer cells. Therefore, future studies should pay attention to the regulation of inflammation-related molecules and signaling pathways in prostate cancer.
