Three cyclic diarylheptanoids, myricanol (1), myricanone (2), and porson (3), were isolated from Myrica javanica (Myricaceae). As a major component, myricanol (1) was obtained from dry powdered bark and twigs (up to 1.6%). Transformation of myricanol (1) afforded 5-prenylmyricanol (4) and 5-benzylmyricanol (5) in 84.5% and 65% yields, respectively. The bioactivities of the isolated cyclic diarylheptanoids and their derivatives were investigated to determine their cytotoxicity and DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activities. The cytotoxicity assay against murine leukaemia P-388 cells demonstrated that compounds 4 and 5 showed an almost two-fold increase in the activity of their parent molecule (1), with an IC50 value of 12 µM. Furthermore, the free radical scavenging assay showed that myricanol (1) had the highest radical scavenging activity, revealing the importance of the free phenolic group (IC50 39.3 µM).

Inhibition of human dihydroorotate dehydrogenase (hDHODH) represents a promising strategy for suppressing the proliferation of cancer cells. To identify novel and potent hDHODH inhibitors, a total of 28 piperine derivatives were designed and synthesized. Their cytotoxicities against three human cancer cell lines (NCI-H226, HCT-116, and MDA-MB-231) and hDHODH inhibitory activities were also evaluated. Among them, compound H19, exhibited the strongest inhibitory activities (NCI-H226 IC50 = 0.95 µM, hDHODH IC50 = 0.21 µM). Further pharmacological investigations revealed that H19 exerted anticancer effects by inducing ferroptosis in NCI-H226 cells, with its cytotoxicity being reversed by ferroptosis inhibitors. This was supported by the intracellular growth or decline of ferroptosis markers, including lipid peroxidation, Fe2+, GSH, and 4-HNE. Overall, H19 emerges as a promising hDHODH inhibitor with potential anticancer properties warranting development.

The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the case with other chemotherapeutic agents, resistance development constrains their effectiveness. One putative mechanism of resistance is the promotion of autophagy, which is a direct consequence of the inhibition of the mTOR signaling pathway. Autophagy is primarily considered to be a cytoprotective survival mechanism, whereby cytoplasmic components are recycled to generate energy and metabolic intermediates. The autophagy induced by everolimus and temsirolimus appears to play a largely protective function, whereas a cytotoxic function appears to predominate in the case of rapamycin. In this review we provide an overview of the autophagy induced in response to mTOR inhibitors in different tumor models in an effort to determine whether autophagy targeting could be of clinical utility as adjuvant therapy in association with mTOR inhibition.

Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, β-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC50 values ranging from 2.35 to 17.06 μM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC50 values of 15.12 ± 0.53 and 12.92 ± 0.60 μM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC50 values of 23.56 ± 0.99 μM, compared to the positive control L-NMMA with an IC50 value of 41.11 ± 1.34 μM.

One previously undescribed abietane diterpene alkaloid containing an oxazole ring (1), one unreported abietane diterpene (2), and nine known abietane diterpenes (3-11) were isolated from the roots and rhizomes of Salvia castanea Diels. Their structures and absolute configurations were elucidated by a combination of HRESIMS, 1D and 2D NMR, and ECD. All compounds were evaluated for their cytotoxic activity against several human cancer cell lines (HepG2, A549, H460, MCF7, PC3, and Hela). The results showed that 1 exhibited a moderate cytotoxic effect on HepG2 cells (IC50: 14.22 ± 1.05 μM) and was able to inhibit the cell growth of MCF7 and Hela cells by 35.08% and 47.26% respectively, at a concentration of 20 μM, while other compounds showed low cytotoxic activity.

Liver cancer ranks among the most prevalent malignancies globally and stands as a leading cause of cancer-related mortality. Numerous isothiazolone derivatives and analogues have been synthesized and investigated for their potential as anticancer agents; however, limited data exist regarding their efficacy against liver cancer. In the present study, two nitrophenyl-isothiazolones, the 5-benzoyl-2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoA) and the 2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoB), were preliminarily investigated for their cytotoxicity against hepatoma human (Huh7) cells as a liver cancer model and Immortalized Human Hepatocytes (IHHs) as a model of non-cancerous hepatocytes. IsoB, derived from IsoA after removal of the benzoyl moiety, demonstrated the highest cytotoxic effect against Huh7 cells with CC50 values of 19.3 μΜ at 24 h, 16.4 μΜ at 48 h, and 16.2 μΜ at 72 h of incubation, respectively. IsoB also exhibited selective toxicity against the liver cancerous Huh7 cells compared to IHH cells, reinforcing its role as a potent and selective anticancer agent. Remarkably, the cytotoxicity of IsoB was higher when compared with the standard chemotherapeutical agent 5-fluorouracil (5-FU), which also failed to exhibit higher toxicity against the liver cancerous cell lines. Moreover, IsoB-treated Huh7 cells presented a noteworthy reduction in mitochondrial membrane potential (ΔΨm) after 48 and 72 h, while mitochondrial superoxide levels showed an increase after 24 h of incubation. The molecular mechanism of the IsoB cytotoxic effect was also investigated using RT-qPCR, revealing an apoptosis-mediated cell death along with tumor suppressor TP53 overexpression and key-oncogene MYCN downregulation.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

Sprouts\' consumption has become popular due to their wide availability, easy cultivation process, and proven biological activity. Moreover, stress factors, such as limited access to light or disturbed gravity during growth, may contribute to the increased activity and the synthesis of bioactive compounds. In this study, for the first time, the examination of the impact of darkness and simulated microgravity conditions on the white clover sprouts from the Fabaceae family was conducted. Among several species, used in the preliminary attempts, only white clover was satisfactory sprouting in the disturbed gravity conditions, and thus was chosen for further examination. A random positioning machine setup was used during the cultivation process to simulate microgravity conditions. Additionally, the sprouts were cultivated in total darkness. Simulated microgravity and/or darkness during the first few days of the sprouts\' growth caused biomass reduction, the increased synthesis of bioactive compounds (isoflavones and phenolics), and changes in the level of abscisic acid and phenylalanine ammonia-lyase. Moreover, it increased the antioxidant properties of the sprouts, while the enhancement of their cytotoxic impact was observed only for androgen-dependent prostate cancer LNCaP cells. To conclude, the presented results are promising in searching for novel functional food candidates and further studies are necessary, directed at other plant families.

Cancer is a disease resulting from the disruption of cell cycle regulation, leading to the abnormal and unchecked proliferation of cells. Medicinal plants are rich in various bioactive phytochemicals or nutritional compounds. The aim is to determine the cytotoxic and genotoxic effects of ethanolic extracts of Macaranga peltata leaves on human oral cancer cell lines. The study setting was centre for Research on Molecular and Applied Sciences, Azeezia College of Dental Sciences and Research. The study design is a Comparative In Vitro study. Shade dried leaves of Macaranga peltata were subjected to Soxhlet extraction, and ethanolic extract was prepared. In vitro cytotoxic effects on human oral cancer cell lines were evaluated by (3-(4,5-dimethyl thiazole-2yl)-2,5-diphenyl tetrazolium bromide) MTT assay, and genotoxic effect was evaluated by comet assay. Untreated cell lines were used as control, and 5-fluorouracil was used as positive control. All experiments were performed in triplicates, and results were represented as Mean+/- SE. One-way ANOVA and Dunnet test were performed to analyze data. ***P < 0.001 compared with the control group. The ethanolic extract of Macaranga peltata exhibited cytotoxicity against oral cancer cells (LC50: 40.193089 μg/ml). There was a concentration-dependent increase in cell death, and at 100 μg/ml, the extract was most effective, causing 50% inhibition of viability. The comet assay showed significant genotoxic effects compared with 5-fluorouracil and untreated oral cancer cell lines. The ethanolic extract of Macaranga peltata leaves was subjected to MTT assay and comet using KB cell lines. The study concludes that the extract gave promising result for the anticancer activity on the KB cell lines producing cytotoxicity and genotoxicity.

OBJECTIVE: This study aimed to investigate the cytotoxicity effect of the ethyl acetate extract of Aaptos suberitoides on colorectal cancer cells (DLD-1) and murine fibroblast cells (NIH-3T3).
METHODS: A. suberitoides was collected from Putus Island, Bunaken National Park, North Sulawesi, Indonesia, and was processed with maceration and ethyl acetate extraction. The sponge extract was characterized based on Thin Layer Chromatography (TLC) and then identified by using LCMS/MS analysis. DLD-1 and NIH-3T3 cells were treated with the ethyl acetate extract and then followed by 3- [4, 5-dimethylthiazol-2-yl] -2.5 diphenyl tetrazolium bromide (MTT) assay to assess their cytotoxicity effect.
RESULTS: LCMS/MS analysis showed that the most abundant compounds in this extract were identified as aaptamine (1). Furthermore, this study revealed that the active ethyl acetate fraction of A. suberitoides has cytotoxic effects in colorectal cancer DLD-1 cells with an IC50 value of 9.597 µg/mL, higher than NIH-3T3 cells with an IC50 value of 12.23 µg/mL Thus, the active ethyl acetate fraction of A. suberitoides is considered more toxic to cancer cells than normal cells.
CONCLUSIONS: This study provides the first evidence to support the role of the ethyl acetate extract of A. suberitoides sponge extracts to be developed as a colorectal anticancer agent.