Anticancer Potential of Indole Phytoalexins and Their Analogues.

Indole phytoalexins, found in economically significant Cruciferae family plants, are synthesized in response to pathogen attacks or stress, serving as crucial components of plant defense mechanisms against bacterial and fungal infections. Furthermore, recent research indicates that these compounds hold promise for improving human health, particularly in terms of potential anticancer effects that have been observed in various studies. Since our last comprehensive overview in 2016 focusing on the antiproliferative effects of these substances, brassinin and camalexin have been the most extensively studied. This review analyses the multifaceted pharmacological effects of brassinin and camalexin, highlighting their anticancer potential. In this article, we also provide an overview of the antiproliferative activity of new synthetic analogs of indole phytoalexins, which were synthesized and tested at our university with the aim of enhancing efficacy compared to the parent compound.

Exploring the Antiproliferative and Modulatory Effects of 1-Methoxyisobrassinin on Ovarian Cancer Cells: Insights into Cell Cycle Regulation, Apoptosis, Autophagy, and Its Interactions with NAC.

Ovarian cancer, a highly lethal malignancy among reproductive organ cancers, poses a significant challenge with its high mortality rate, particularly in advanced-stage cases resistant to platinum-based chemotherapy. This study explores the potential therapeutic efficacy of 1-methoxyisobrassinin (MB-591), a derivative of indole phytoalexins found in Cruciferae family plants, on both cisplatin-sensitive (A2780) and cisplatin-resistant ovarian cancer cells (A2780 cis). The findings reveal that MB-591 exhibits an antiproliferative effect on both cell lines, with significantly increased potency against cisplatin-sensitive cells. The substance induces alterations in the distribution of the cell cycle, particularly in the S and G2/M phases, accompanied by changes in key regulatory proteins. Moreover, MB-591 triggers apoptosis in both cell lines, involving caspase-9 cleavage, PARP cleavage induction, and DNA damage, accompanied by the generation of reactive oxygen species (ROS) and mitochondrial dysfunction. Notably, the substance selectively induces autophagy in cisplatin-resistant cells, suggesting potential targeted therapeutic applications. The study further explores the interplay between MB-591 and antioxidant N-acetylcysteine (NAC), in modulating cellular processes. NAC demonstrates a protective effect against MB-591-induced cytotoxicity, affecting cell cycle distribution and apoptosis-related proteins. Additionally, NAC exhibits inhibitory effects on autophagy initiation in cisplatin-resistant cells, suggesting its potential role in overcoming resistance mechanisms.

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence.

Cancer is a complex and multifaceted disease with a high global incidence and mortality rate. Although cancer therapy has evolved significantly over the years, numerous challenges persist on the path to effectively combating this multifaceted disease. Natural compounds derived from plants, fungi, or marine organisms have garnered considerable attention as potential therapeutic agents in the field of cancer research. Ellagic acid (EA), a natural polyphenolic compound found in various fruits and nuts, has emerged as a potential cancer prevention and treatment agent. This review summarizes the experimental evidence supporting the role of EA in targeting key hallmarks of cancer, including proliferation, angiogenesis, apoptosis evasion, immune evasion, inflammation, genomic instability, and more. We discuss the molecular mechanisms by which EA modulates signaling pathways and molecular targets involved in these cancer hallmarks, based on in vitro and in vivo studies. The multifaceted actions of EA make it a promising candidate for cancer prevention and therapy. Understanding its impact on cancer biology can pave the way for developing novel strategies to combat this complex disease.

Antiproliferative Effect of Phellodendron amurense Rupr. Based on Angiogenesis.

Phellodendron amurense Rupr. is medicinal plant used for supplemental therapy of various diseases based on their positive biological activities. The aim of this study was evaluated the main metabolite, safety of application and anticancer potential. Berberine was determined by HPLC as main alkaloid. Harmful character was determined by irritation test in ovo. The potential cancerogenic effect was studied in vitro on a cellular level, in ovo by CAM assay and in vivo on whole organism Artemia franciscana. Extract from the bark of Phellodendron amurense showed antiproliferative and antiangiogenic effects. The results of our work showed promising anticancer effects based also on the inhibition of angiogenesis with minimum negative effects.

Diversity, distribution and changes in communities of fleas on small mammals along the elevational gradient from the Pannonian Plain to the Carpathian Mountains.

The causal chain of parasite-host-environment interactions, the so-called 'dual parasite environment', makes studying parasites more complicated than other wild organisms. A sample of 65 282 fleas taken from 336 different locations were analysed for changes in the distribution, diversity and compensation of flea communities found on small mammals along an elevational diversity gradient ranging from the Pannonian Plain to the base of the Carpathian summits. The fleas were divided into four groups, which were derived from changes in abundance and occurrence determined from cluster analysis. They are (1) flea species whose range seems unrelated to any change in elevation; (2) species that avoid high altitudes; (3) a group that can be subdivided into two types: (i) host-specific fleas and (ii) mountains species and (4) species opting for high altitudes on the gradient or preferring lower to middle elevations below 1000 m. Our study showed a unimodal pattern of flea diversity along the elevational gradient. It indicated that seasonality significantly conditions changes in biodiversity and patterns of spatial change along the elevational gradient, with specific flea species influenced by their host, while the impact of environmental conditions is more pronounced in opportunistic flea species.

Naja ashei venom induces mitochondria-mediated apoptosis in human colorectal cancer cells.

In the present study, we investigated the antiproliferative activity of Naja ashei full venom (NAV) on human colorectal cancer cells. The NAV-induced antiproliferative effect was associated with cell cycle arrest in S phase and increased number of cells with sub G0/G1 DNA content, which is considered a marker of apoptosis. Apoptosis has also been confirmed with annexin V/PI staining. Furthermore, flow cytometric analysis revealed loss of mitochondrial membrane potential with concomitant increase in cytochrome c and Smac/DIABLO protein content. These effects were associated with the activation of caspase-9 and caspase-3, as well as with PARP cleavage. Moreover, phosphorylation of antiapoptotic Bcl-2 protein in NAV-treated HCT116 was observed. In conclusion, our study for the first time documented antiproliferative/pro-apoptotic effect of NAV in colorectal cancer cells. Our results strongly suggest the involvement of mitochondria in NAV induced apoptosis of cancer cells. Future studies are needed to further examine the potential of NAV in the treatment of colon cancer.