salvianolic-acid-B and Neoplasms

LSD1 was significantly over-expressed in several cancer types, and its aberrant overexpression was revealed to play a crucial role in the initiation and progression of cancer. Several LSD1 inhibitors that were discovered and developed so far were found to be effective in attenuating tumor growth in both in vivo and in vitro studies. However, the major challenge associated with the development of cancer therapies is personalized treatment. Therefore, it is essential to look in detail at how LSD1 plays its part in carcinogenesis and whether there are any different expression levels of LSD1 in different tumors. Here in this review, fresh insight into a list of function correlated LSD1 binding proteins are provided, and we tried to figure out the role of LSD1 in different cancer types, including hematological malignancies and solid tumors. A critical description of mutation preference for LSD1 in different tumors was also discussed. Recent research findings clearly showed that the abrogation of LSD1 demethylase activity via LSD1 inhibitors markedly reduced the growth of cancer cells. But there are still many ambiguities regarding the role of LSD1 in different cancers. Therefore, targeting LSD1 for treating different cancers is still reductionist, and many challenges need to be met to improve the therapeutic outcomes of LSD1 inhibitors.

Topics: Carcinogenesis; Histone Demethylases; Humans; Neoplasms

Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising target for the discovery of specific inhibitors as antitumor drugs. Based on the source of compounds, all LSD1 inhibitors in this review are divided into two categories: natural LSD1 inhibitors and synthetic LSD1 inhibitors. This review highlights the research progress of LSD1 inhibitors with the potential to treat cancer covering articles published in 2020. Design strategies, structure-activity relationships, co-crystal structure analysis and action mechanisms are also highlighted.

Topics: Antineoplastic Agents, Phytogenic; Enzyme Inhibitors; Histone Demethylases; Humans; Molecular Structure; Neoplasms

The cancer photodynamic therapy (PDT) is limited by a congenital defect, namely the tumor hypoxia. Cancer cells are characterized by the vigorous oxygen-consuming glycolysis, which is well-known as the "Warburg effect" and one of the primary causes for the hypoxia. Herein, we employed the glucose metabolism as the cancer-specific target to enhance the performance of PDT. The Salvianolic acid B as the inhibitor of glucose uptake and aerobic glycolysis was concomitantly delivered with the photosensitizer chlorin e6 by a redox-responsive organosilica cross-linked micelle. The results demonstrated that the Salvianolic acid B suppressed the glucose metabolism, retarded the oxygen consumption to retain adequate oxygen as the ammo for PDT, which remarkably improve the efficacy of PDT both in vitro and in vivo. Our study not only provides an alternative strategy to address the hypoxia problem for PDT, but also enhances the selectivity of the treatment by targeting the cancer-specific Warburg effect.

Topics: Cell Line, Tumor; Glucose; Humans; Hypoxia; Nanoparticles; Neoplasms; Oxygen; Photochemotherapy; Photosensitizing Agents; Porphyrins

As the key stromal cells that mediate the desmoplastic reaction, tumor-associated fibroblasts (TAFs) play a critical role in the limited nanoparticle penetration and suppressive immune tumor microenvironment. Herein, we found that salvianolic acid B-loaded PEGylated liposomes (PEG-SAB-Lip) can interfere with the activation of TAFs by inhibiting the secretion of TGF-β1. After inhibiting the activation of TAFs, collagen deposition in tumors was reduced, and the penetration of nanoparticles in tumors was enhanced. The results of RT-qPCR and immunofluorescence staining showed the high expression of Th1 cytokines and chemokines (CXCL9 and CXCL10) and the recruitment of CD4

Topics: Benzofurans; Cancer-Associated Fibroblasts; CD8-Positive T-Lymphocytes; Fibroblasts; Humans; Immunologic Factors; Immunotherapy; Liposomes; Neoplasms; Smad Proteins; Transforming Growth Factor beta1; Tumor Microenvironment

Tumor vasculature is characterized by aberrant structure and function, resulting in immune suppressive profiles of tumor microenvironment (TME) through limiting immune cell infiltration into tumors. The defective vascular perfusion in tumors also impairs the delivery and efficacy of chemotherapeutic agents. Targeting abnormal tumor blood vessels has emerged as an effective therapeutic strategy to improve the outcome of chemotherapy and immunotherapy. In this study, we demonstrated that Salvianolic acid B (SalB), one of the major ingredients of Salvia miltiorriza elicited vascular normalization in the mouse models of breast cancer, contributing to improved delivery and response of chemotherapeutic agent cisplatin as well as attenuated metastasis. Moreover, SalB in combination with anti-PD-L1 blockade retarded tumor growth, which was mainly due to elevated infiltration of immune effector cells and boosted delivery of anti-PD-L1 into tumors. Mechanistically, tumor cell enhancer of zeste homolog 2 (Ezh2)-driven cytokines disrupted the endothelial junctions with diminished VE-cadherin expression, which could be rescued in the presence of SalB. The restored vascular integrity by SalB via modulating the interactions between tumor cells and endothelial cells (ECs) offered a principal route for achieving vascular normalization. Taken together, our data elucidated that SalB enhanced sensitivity of tumor cells to chemotherapy and immunotherapy through triggering tumor vascular normalization, providing a potential therapeutic strategy of combining SalB and chemotherapy or immunotherapy for patients with breast cancer.

Topics: Animals; Antineoplastic Agents; Benzofurans; Cisplatin; Endothelial Cells; Enhancer of Zeste Homolog 2 Protein; Immunologic Factors; Immunotherapy; Mice; Neoplasms; T-Lymphocytes; Tumor Microenvironment