Hepatocellular carcinoma (HCC) causes 830000 deaths every year and is becoming the third malignant tumor worldwide. One of the primary reasons is the lack of effective drugs. Hernandezine (HER), a bisbenzylisoquinoline alkaloid of Thalictrum simplex, has been confirmed to have antitumor activity. But there are few reports about its effect on HCC and the underlying mechanisms still remain unclear. Therefore, the antitumor effects and mechanisms of HER on HCC were evaluated in HepG2 and Hep3B cells. The in vitro experiments demonstrated that HER significantly induced G0/G1 phase arrest, inhibited the proliferation and promoted cell apoptosis in liver cancer cell lines. In the mechanisms, the antitumor effects of HER on liver cancer cells were mediated by phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) pathway and reactive oxygen species (ROS), simultaneously. In one way, HER inhibited the activities of PI3K-AKT pathway, which interrupt the dimer formation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 (CCND1) and result to G0/G1 phase arrest. In another way, after HER treatment, ROS accumulated in liver cancer cells and caused mitochondria injury which further influenced the expression of apoptosis-related proteins and eventually resulted to HepG2 and Hep3B cell apoptosis. In addition, HER showed a tumor restrain function in HepG2 and Hep3B bearing nude mice. Overall, these findings indicated that HER is a promising antitumor drug, which may provide a new direction for clinical HCC treatment.
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http://dx.doi.org/10.1248/bpb.b22-00612 | DOI Listing |
J Nat Prod
January 2025
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 03 Hradec Kralove, Czech Republic.
An activity-guided isolation study on the EtOH extract prepared from the bulbs of yielded four new phenolic compounds, including a new stilbenoid (), a new homoisoflavonoid derivative (), a new homoisoflavonoid dimer (), and an unprecedented homoisoflavone-stilbene heterodimer (), together with six known (-) analogs. Their chemical structures were elucidated by spectroscopic analysis and theoretical NMR and ECD calculations. Compounds and are unique in their scaffolds.
View Article and Find Full Text PDFToxicology
January 2025
Department of Pharmacology, Shantou University Medical College, Shantou 515041, China. Electronic address:
Aflatoxin B1 (AFB1) has been reported to synergize with hepatitis B virus (HBV) to induce development of hepatocellular carcinoma (HCC). Precise daily exposure to AFB1 and its contribution to liver injury have not been quantified and have even been disregarded due to lack of convenient detection, and the strong species specificity of HBV infection has restricted research on their synergistic harm. Hence, our objective was to investigate the molecular mechanisms by which AFB1 exacerbates HBV-related injury.
View Article and Find Full Text PDFComput Biol Chem
December 2024
Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address:
Clinical observations indicate a pronounced exacerbation of Cardiovascular Diseases (CVDs) in individuals grappling with Alcohol Use Disorder (AUD), suggesting an intricate interplay between these maladies. Pinpointing shared risk factors for both conditions has proven elusive. To address this, we pioneered a sophisticated bioinformatics framework and network-based strategy to unearth genes exhibiting aberrant expression patterns in both AUD and CVDs.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Life Sciences, College of Life Sciences, National Chung Hsing University, Kuo Kuang Rd., Taichung, 402, Taiwan.
Hepatocellular carcinoma (HCC) constitutes 90% of liver cancer cases and ranks as the third leading cause of cancer-related mortality, necessitating urgent development of alternative therapies. Lactoferrin (LF), a natural iron-binding glycoprotein with reported anticancer effects, is investigated for its potential in liver cancer treatment, an area with limited existing studies. This study focuses on evaluating LF's anti-liver cancer effects on HCC cells and assessing the preventive efficacy of oral LF administration in a murine model.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Medical Biochemistry, Trakya University School of Medicine, Edirne, 22030, Turkey.
We aimed to determine the effects of piperine on cell viability, cellular stresses, and apoptosis first, then the relationship of piperine's effects with the c-Jun N-terminal kinase (JNK) signaling pathway, and also the interaction of piperine with sorafenib in hepatocellular carcinoma. Hepatocellular carcinoma (HepG2 and Hep3B) and non-cancerous hepatocyte (AML12) cell lines were used. The cell viability was determined by using MTT assay.
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