Dihydroaustrasulfone Alcohol Induces Biphasic Autophagy and Apoptosis in Leukemia Cells via PI3K/Akt and JNK Signaling Pathways

Oregano extract induces apoptosis and inhibits autophagy in HepG2 cells via the PI3K/AKT pathway

Hepatocellular carcinoma (HCC) remains one of the most common and highly lethal malignancies globally. Conventional therapeutic approaches are often limited by suboptimal efficacy and significant toxicity, driving the search for alternative strategies, particularly those derived from natural products. This study aimed to evaluate the antitumor activity and underlying molecular mechanisms of the ethyl acetate extract of “Origanum vulgare” L (EAO) in human hepatocellular carcinoma cells. Our findings demonstrate that EAO markedly suppressed HepG2 and Huh7 cell proliferation and promoted apoptosis, accompanied by increased reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential, and ATP depletion. Additionally, EAO inhibited autophagy, as indicated by decreased LC3-II expression and increased p62 accumulation. Mechanistic investigations revealed that EAO inactivated the PI3K/AKT signaling pathway, and these effects were reversed by the ROS scavenger N-acetylcysteine (NAC), confirming ROS-dependent suppression of this pathway. Both network pharmacology and RNA-sequencing analyses further supported PI3K/AKT as a critical regulatory node. In summary, EAO exerts potent antitumor effects against hepatocellular carcinoma by inducing mitochondrial dysfunction and apoptosis, while concurrently suppressing autophagy through ROS-mediated inhibition of the PI3K/AKT pathway. These results highlight EAO as a promising low-toxicity candidate for the treatment of liver cancer.

10-HDA Suppresses the Growth of Gastric Cancer Cells Through Inducing Apoptosis and G0/G1 Cell Cycle Arrest

Background/Objectives: Gastric cancer (GC) remains a major global health challenge, highlighting the need for safe and effective bioactive compounds for prevention and treatment. Although 10-hydroxy-2-decenoic acid (10-HDA)—a distinctive bioactive fatty component of royal jelly—has demonstrated anticancer activity in several malignancies, its efficacy and underlying mechanisms in GC remain poorly understood. In the present study, the anticancer activity of 10-HDA was systematically investigated in human GC MKN-45 cells. Methods: MKN-45 cells were treated with 10-HDA across a concentration range of 0.09–1.50 mM. Cell viability, proliferation, and clonogenic growth were evaluated using MTT, scratch wound assay, and colony formation assays. Apoptosis was analyzed by flow cytometry and Western blotting. To explore the underlying molecular mechanisms, transcriptome analysis was conducted, and the results were further validated using flow cytometry, qRT-PCR, and Western blotting. Results: Treatment with 10-HDA significantly inhibited cell viability, proliferation, and clonogenic growth in a dose- and time-dependent manner, with IC50 values of 1.24 ± 0.15 mM, 0.96 ± 0.08 mM, and 0.42 ± 0.06 mM at 24 h, 48 h, and 72 h, respectively. Flow cytometric analysis revealed that apoptosis was markedly induced, with the apoptotic rate increasing from 21.3% in control cells to 78.1% following treatment with 1.50 mM 10-HDA. This was accompanied by upregulation of BAX, downregulation of Bcl-2, and increased activation of caspase-3. Transcriptomic profiling identified significant alterations in DNA replication- and cell cycle-related pathways. Consistently, experimental validation demonstrated that 10-HDA induced pronounced G0/G1-phase cell cycle arrest; downregulation of CDK2 and cyclin D1; reduced retinoblastoma protein phosphorylation; and upregulation of the cyclin-dependent kinase inhibitor CDKN1A. Conclusions: These findings demonstrate that 10-HDA suppresses the malignant phenotype of gastric cancer cells by coordinated activation of apoptosis and cell cycle blockade. Although further in vivo studies and pharmacological experiments are required to evaluate its bioavailability and therapeutic potential, this study provides preliminary mechanistic insights into the effects of 10-HDA on gastric cancer cells.

Hepatocellular Carcinoma Activity by Targeting Multiple Oncogenic Pathways

Jolkinolide B induces apoptosis and G1 arrest in A549 cells via JAK2/STAT3 inhibition.

BACKGROUND Lung cancer is the most common pulmonary malignancy. WHO data show that its incidence and mortality are rising globally, severely threatening public health. OBJECTIVES This study aims to investigate the regulatory effect of Jolkinolide B (JB) on lung cancer A549 cells and to preliminarily explore the potential molecular mechanisms underlying its anti-lung cancer effects. METHODS In this study, A549 lung adenocarcinoma cells were used to investigate the anti-lung cancer effects of JB. CCK-8 and colony formation assays were performed to evaluate cell proliferation. Molecular docking and molecular dynamics simulation were applied to verify the binding between JB and JAK2, while Western blot was used to detect the expression of JAK2/STAT3 pathway-related proteins. Flow cytometry, immunofluorescence and Western blot were employed to explore the regulatory roles of JB in cell apoptosis and cycle. In addition, a nude mouse xenograft model was established and HE staining and immunohistochemistry were used to verify the in-vivo efficacy of JB. All data were statistically analyzed using GraphPad Prism and SPSS. RESULTS The results demonstrated that JB inhibited A549 cell proliferation in a dose‑dependent manner with an IC50 of 39.34 μM at 24 h. JB bound stably to JAK2 (PDB: 7RN6) with a binding free energy of -8.33 kcal/mol and suppressed the JAK2/STAT3 pathway. JB significantly promoted apoptosis and induced G1‑phase arrest via regulating P21, Cyclin D1, BAX, Caspase 3, PARP1 and Bcl‑2. In-vivo, JB reduced tumor growth in a dose‑dependent manner, induced tumor cell necrosis and downregulated p‑JAK2 and p‑STAT3 expression. CONCLUSION Jolkinolide B can significantly inhibit the proliferation of human lung adenocarcinoma A549 cells. Its mechanism of action is closely related to inducing cell cycle arrest and promoting cell apoptosis. The above effects may be partially achieved by inhibiting the JAK2/STAT3 pathway. In animal experiments, JB also significantly inhibits the growth of lung cancer transplanted tumors.

Molecular mechanism by which dichotomitin inhibits growth and metastasis of gastric cancer MKN-45 cells via the EGFR/ROS signaling pathway.

INTRODUCTION Dichotomitin (DC), an isoflavone from Belamcanda chinensis, has anti-inflammatory and antioxidant properties, but its role in gastric cancer (GC) remains unexplored. This study aimed to elucidate the mechanisms by which DC modulates GC cell proliferation, apoptosis, and migration. MATERIALS AND METHODS . MKN-45 cells were used for in vitro studies, and xenograft tumor models were established using BALB/c nude mice for in vivo evaluation. Bioinformatics analysis predicted core targets. CCK-8, flow cytometry, wound healing, Transwell, and fluorescence microscopy assays were performed to assess proliferation, cell-cycle distribution, apoptosis, migration, and ROS levels. Expression of proteins in the EGFR/MAPK, EGFR/AKT, and AKT/GSK-3β/β-catenin pathways was determined by Western blotting. RESULTS . In vitro, DC significantly inhibited GC cell proliferation and induced morphological changes. DC induced cell cycle arrest in the G0/G1 phase and promoted mitochondria-dependent apoptosis by modulating EGFR/MAPK signaling, while inhibiting migration through the AKT/GSK-3β/β-catenin pathway. Mechanistically, DC inhibited EGFR activation and elevated ROS levels. The EGFR agonist NSC228155 reversed these effects, confirming dependence on EGFR-ROS signaling. In vivo, DC dose‑dependently inhibited tumor growth, with medium/high doses outperforming 5‑fluorouracil. Histological examination of major organs showed no significant abnormalities, confirming low toxicity at therapeutic doses. CONCLUSIONS . DC inhibited proliferation, induced cell cycle arrest and apoptosis, and suppressed migration in GC cells by modulating EGFR-related ROS-dependent signaling pathways.

Homoharringtonine in combination with Tanshinone IIA suppresses the progression of lymphoma cells by downregulating the Akt/MMP signaling pathway

HHT and Tan IIA combined therapy synergistically suppressed lymphoma progression by downregulating the Akt/MMP signaling pathway, suggesting their use in treating lymphomas.