The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance, rendering them with limited therapies. To discover new regimens for the treatment of PCa including resistant PCa, natural products, the richest source of bioactive compounds, can serve as a library for screening and identifying promising candidates, and flavones such as apigenin and genistein have been used in lab and clinical trials for treating PCa over decades. In this mini-review, we take a look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade. While possessing very similar structure, these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells. Given that more combinations are being developed and tested, genistein appears to be the more promising option to be approved. The anticancer efficacies of these two flavones can be confirmed by in-vitro and in-vivo studies, and their applications remain to be validated in clinical trials. Information gained in this work may provide important information for new drug development and the potential application of apigenin and genistein in treating PCa.

S100 calcium-binding protein A11 (S100A11) has been proved to be an oncogene of most tumors. However, its role in the tumor microenvironment (TME) in pan-cancer stills remains poorly understood. This study used public data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to evaluate the expression of S100A11. The R package “GSVA” was used for Gene set variation analysis (GSVA) of S100A11. The R package “ESTIMATE” was used to further explore the relationship between S100A11 and TME. The Genomics of Drug Sensitivity in Cancer database was used to investigate the effect of S100A11 on the efficiency of anticancer drugs. We found S100A11 expression was upregulated in most tumors and predicted a poor prognosis. Furthermore, S100A11 expression was closely associated with immune regulation-related pathways. Moreover, S100A11 expression in pan-cancer was significantly related to most immunosuppressive cells, such as tumor-associated macrophages (TAM), tumor-associated fibroblasts (TAF), and Treg cells. The expression of S100A11 was significantly related to immunosuppressive genes and immune checkpoints in most tumor types. Additionally, the upregulation of S100A11 expression made patients with cancer resistant to the treatment of most anticancer drugs, such as sorafenib. In brief, our study showed that S100A11 could be used as a potential carcinogen and prognostic marker for most tumor types. The increased expression of S100A11 was closely related to tumor immunosuppressive TME. The upregulation of S100A11 expression made patients with cancer resistant to sorafenib treatment.

Efficient screening of anticancer agents is in urgent need to develop new drugs that combat malignant tumors and drug resistance. In this study, a combined strategy composed by solvent partition and HPLC fractionation was developed to generate an herbal fraction library of Salviae Miltiorrhizae Radix et Rhizoma to quickly and efficiently screen anticancer agents. All library entries are directed into 96 well plates which are well mapped with HPLC chromatograms. The cell proliferation assay revealed seven active subfractions. Then, the major active ten peaks in these subfractions were prepared and isolated by semipreparative HPLC, and their inhibitory activities against prostate cancer cells were then tested at the same concentration level, leading to the identification of several active compounds. In addition, the structures of compounds arucadiol (2), 15,16-dihydrotanshinone I (4), methyl tanshinonate (5), cryptanshinone (7), 1,2-dihydrotanshinquinone I (9), and tanshinone IIA (10) were characterized by mass spectrometry and X-ray crystallographic analysis, and they were confirmed to be active in suppressing prostate cancer cell proliferation at 7.5 or 15 μg/mL, among which, the minor compounds 2, 4, and 5 showed higher activities than 9 and 10. This study provided a rapid strategy of identifying new anticancer agents in Salviae Miltiorrhizae Radix et Rhizoma, which can be applied in other herbal medicines.