Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) - Current Issue

With increasing duration of treatment, many tumours gradually develop drug resistance. Therefore, novel antitumour drugs need to be developed to treat patients with tumours. Targeting c-met inhibitors may be an effective treatment strategy.

Scientific databases such as ScienceDirect, PubMed, the Wiley Online Library, and Social Sciences Citation Index were used to collect information. All the relevant literature was reviewed, and the available literature was screened. The upstream and downstream pathways of c-Met and their relevance to antitumour effects were searched based on the articles' title, abstract, and full text. The c-Met-targeting drugs with antitumour effects are summarized below. A “citation within a citation” or snowballing approach was used in this screening process to identify additional papers that may have been missed in the initial literature screening process. High-quality studies published in peer-reviewed journals were summarized and prioritized for citation in the review.

In recent years, research on small-molecule targeted drugs has developed rapidly. Many results have also been achieved in the synthesis and isolation of c-Met inhibitors from natural compounds and traditional Chinese medicines.

This article summarizes the developments in anti-c-Met drugs, which are synthesized and isolated from natural compounds and traditional Chinese medicine (TCM). This study provides primary resources for the development of c-Met inhibitors.

Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named Schisandra rubriflora (Franch.).

In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 in vitro and in vivo.

In vitro, we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. In vivo, we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.

We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 via JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, in vivo observation confirmed the antitumor activity of schisanhenol.

Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 via the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.

Lung cancer is the primary cause of cancer-related deaths globally. Protein kinase B (AKT) protein is associated with many pathways in non-small cell lung cancer (NSCLC), such as proliferation, migration, invasion, and apoptosis. Mushrooms have a long history of being used in traditional medicine to treat various diseases. Scientists have been exploring the potential of mushrooms for their antioxidant and anticancer properties. In our study, the anti-oxidant, invasion, and apoptosis effects of mushroom extracts were investigated in NSCLC.

Non-Small Cell Lung Cancer cell lines H1299, PC-3, and PC-14 were used in our study. After obtaining the extracts of Rhizopogon luteolus and Ganoderma adspersum, IC50 value was calculated as 25.04-11.73-16.54 ng/ul for R. luteolus and 2.97-1.53-1.01 μg/ul for G. adspersum, respectively, in H1299, PC3 and PC14 cell lines. Afterward, proliferative and invasion effects, as well as apoptosis and anti-oxidant effects, were investigated using the IC50 dose. Western blotting was performed to investigate the pathways of these effects.

According to the results of our study, Rhizopogon luteolus and Ganoderma adspersum extracts have anti-proliferative and anti-invasive effects on non-small lung cancer cell lines and induced apoptosis, which has been found to increase the anti-oxidant effect. It was found that this effect was due to cross-talk between antioxidant activity and the AKT-Rb pathway.

We anticipate that Rhizopogon luteolus and Ganoderma adspersum extracts will be effective in cancer treatment by suppressing lung cancer cells via p-Akt and Rb.

Plants and their bioactive compounds play a crucial role in the pharmaceutical industry for treating cancer. To date, the cytotoxic and antiproliferative effects of Hypericum perforatum methanol extract on human thyroid cancer cell lines have not been thoroughly explored. The present study aimed to assess the potential anti-cancer effects of HPME on human thyroid cancer and investigate its potential therapeutic benefits.

HPME was prepared using the maceration method, and its antioxidant activity was examined. Cytotoxicity studies were then carried out, followed by an investigation of the possible effects of HPME on metastasis and colony-forming capacities of human thyroid cancer cells. Afterward, qRT-PCR, western blotting, and apoptosis assays were performed.

Cytotoxicity studies revealed notable cytotoxicity of HPME against the TT cell line. Moreover, HPME significantly curtailed metastasis and invasion of TT cells in an in vitro wound healing assay. Analyses of gene expressions demonstrated an elevation in caspase-12, caspase-3, and Bax, coupled with a reduction in BcL-2, APOE, and CLU expression. Following HPME treatment, there was an increase in the protein expression levels of Bax and Caspase-12, while a decrease in the BcL-2, APOE, and CLU protein expression. Furthermore, apoptotic studies indicated an increase in early apoptosis.

Overall results revealed that HPME demonstrates a notable antioxidant capacity in human thyroid cancer. It exerts an influence on crucial biological processes associated with cancer, indicating its potential to hinder the proliferation of human thyroid cancer cells by enhancing apoptosis through the upregulation of gene and protein expression, particularly involving caspases.