The anticancer mechanism of human antimicrobial peptide LL-37

Human antimicrobial peptides LL-37 have a variety of medicinal uses. It has been portrayed that this peptide has robust tumoricidal action in a range of malignancies, particularly ovarian cancer, lung cancer, breast cancer, prostate cancer, pancreatic cancer, malignant melanoma, and squamous cell carcinoma of the skin. It exhibits substantial anticancer action against a range of cancers, including colon cancer, gastric cancer, hematologic malignancy, and oral squamous cell carcinoma (OSCC), in comparison. In this review, we explored in depth the anticancer mechanism of action of LL-37 in numerous sorts of cancer. We have shown how LL-37 impedes colon cancer by eliciting caspase-independent apoptosis. LL-37, in addition, has been noticed to boost tumor-suppressive bone morphogenetic protein signaling in gastric cancer cells via restricting the proteasome, which has been previously reported. In this research, we investigated how DNA methylation interferes with the activity of the human CAMP (Cathelicidin antimicrobial peptide gene) promoter and, as a result, acts as a tumor inhibitor in mouth squamous cell carcinoma. Additionally, how LL-37 inhibits cancer cell development in hematologic malignancy has been explored through caspase-independent but Ca2+/calpain- and AIF-dependent processes.

The Synthesis, Structural Modification and Mode of Anticancer Action of Evodiamine: a review

Background: Finding novel antitumor reagents from naturally occurring alkaloids is a widely accepted strategy. Evodiamine, a tryptamine indole alkaloid isolated from Evodia rutaecarpa, has a wide range of biological activities, such as antitumor, anti-inflammation, and anti-bacteria. Hence, research works on the structural modification of evodiamine will facilitate the discovery of new antitumor drugs. Objective: The recent advances in the synthesis of evodiamine, and studies on the drug design, biological activities, and structure-activity-relationships of its derivatives, published in patents and primary literatures, are reviewed in this paper. Methods: The literatures, including patents and follow-up research papers from 2015 to 2020, related to evodiamine is searched in the Scifinder, PubMed, Espacenet, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The key words are evodiamine, synthesis, modification, anticancer, mechanism. Results: The synthesis of evodiamine are summarized. Then, structural modifications of evodiamine are described, and the possible modes of actions are discussed. Conclusion: Evodiamine has a 6/5/6/6/6 ring system, and the structural modifications are focused on ring A, D, E, C5, N-13, and N-14. Some compounds show promising anticancer potentials and warrant further study.

Therapeutic Application of Genetically Engineered Ribosome-Inactivating Toxin Proteins for Cancer

Recently, Ribosome-Inactivating Proteins (RIPs) as a class of anticancer medicines have garnered considerable attention due to their novel anticancer mechanism. Although the medications are small, RIPs utilize the Large-Size Effect (LSE) to block the efflux procedure that are regulated through Drug Resistance Transporters (DRTs), and protect host cells from drug transfection. There are many significant challenges for their therapeutic applications that seriously restrict their usefulness, particularly their strategy towards tumor cells. The primary objective of this review is to emphasize Trichosanthin (TCS) along with Gelonin (Gel) and additional types of RIPs, particularly scorpion venom-derived RIPs, to demonstrate that they should be grappling through what kinds of bio-barriers to overcome in cancer therapeutic science. Next, we will emphasize the latest state-of-the-art in providing cancer treatment RIPs.

Synergistic Anti-Tumor Effect of Simvastatin Combined to Chemotherapy in Osteosarcoma

Context: Osteosarcoma is the most common primary solid malignancy of the bone, mainly affecting pediatric patients. The main clinical issues are chemoresistance and metastatic spread, leading to a survival rate stagnating around 60% for four decades. Purpose: Here, we investigated the effect of simvastatin as adjuvant therapy on chemotherapy. Methods: Cell viability was assessed by the MTT test, and a combination index was evaluated by an isobologram approach. Cell motility was assessed by wound-healing assay. Cell-derived xenograft models were established in mice. FFPE tumor samples were assessed by immunohistochemistry. Results: In vitro experiments indicate that simvastatin synergized the conventional chemotherapy drugs' inhibitory effect on cell viability. Functional assays reveal that simvastatin supplementation favored the anticancer mechanism of action of the tested chemotherapy drugs, such as DNA damage through intercalation or direct alkylation and disorganization of microtubules. Additionally, we show that even though simvastatin alone did not modify tumor behavior, it potentiated the inhibitory effect of doxorubicin on primary tumor growth (+50%, p < 0.05) and metastatic spread (+50%, p < 0.05). Our results provide evidence that simvastatin exerted an anti-tumor effect combined with chemotherapy in the preclinical murine model and represents valuable alternative adjuvant therapy that needs further investigation in clinical trials.

Synthetic Optimization and MAPK Pathway Activation Anticancer Mechanism of Polyisoprenylated Cysteinyl Amide Inhibitors

Abnormalities of the MAPK pathway play vital roles in cancer initiation and progression. RAS GTPases that are key upstream mediators of the pathway are mutated in 30% of human cancers. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) were designed as potential targeted therapies against the RAS-driven cancers. The current study reports on the optimization of the PCAIs and the determination of their mechanisms of action in KRAS-mutant cancer cells. They display ClogP values ranging from 3.01 to 6.35, suppressing the viabilities of KRAS-mutant MDA-MB-231, A549, MIA PaCa-2, and NCI-H1299 cells in 2D and 3D cultures with EC50 values of 2.2 to 6.8, 2.2 to 7.6, 2.3 to 6.5 and 5.0 to 14 µM, respectively. When A549 cells were treated with the PCAIs, NSL-YHJ-2-27, for 48 h, no significant difference was observed in the levels of total or phosphorylated B- and C-Raf proteins. However, at 5 µM, it stimulated the phosphorylation of MEK1/2, ERK1/2, and p90RSK by 84%, 59%, and 160%, respectively, relative to controls. A non-farnesylated analog, NSL-YHJ-2-62, did not elicit similar effects. These data reveal that effects on the RAS-MAPK signaling axis most likely contribute to the anticancer effects of the PCAIs, possibly through the proapoptotic isoforms of p90RSK. The PCAIs may thus have the potential to serve the unmet therapeutic needs of patients with aberrant hyperactive G-protein signaling.

Anticancer mechanism of biosynthesized copper oxide nanoparticles (CPNPS)

CPNPS synthesis is an important engine in biomedical research with a scalable scale and desired functionality. Although these props are focused largely on synthetic methods, the advancement accomplished in this area has reported a direct influence on morphology and biomedical characteristics of synthesis and surface modifiers. Sensing is a significant use of nanomaterial in consideration of small dimensions and their peculiar physicochemical characteristics, but the trend has changed over the last few years towards the "teranotic" combination on a single platform of sensing and therapeutic properties. CPNPSs have been used successfully in vivo and in vitro for identification and targeting, but before commercial implementation, several primary obstacles remain.