Cinobufagin, a cardiotonic steroid derived from toad venom extracts, exhibits significant anticancer properties by inhibiting Na[Formula: see text]/K[Formula: see text]-ATPase in cancer cells. It is frequently used in clinical settings to treat advanced-stage cancer patients, improving their quality of life and survival time. However, its long-term use can result in multidrug resistance to other chemotherapy drugs, and the exact mechanism underlying this effect remains unknown. Therefore, this study explores the molecular mechanism underlying the anticancer effects of cinobufagin in hepatocellular carcinomas (HCCs), specifically in HepG2 and Huh-7 cells. As determined using transcriptome analysis, cinobufagin-triggered protective autophagy suppressed cell apoptosis in liver cancer HepG2 and Huh-7 cells by inhibiting the phosphoinositide-3-Kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway. Cinobufagin-inhibited cell proliferation, induced apoptosis, and generated cell autophagy by upregulating the expression of MAP1 light chain 3 protein II, Beclin1, and autophagy-related protein 12-5. In addition, the autophagy inhibitor MRT68921 improved the antiproliferative and proapoptotic effects of cinobufagin in the studied cell lines. Overall, this study suggests that combining cinobufagin with an autophagy inhibitor can effectively treat HCC, providing a potential strategy for cancer therapy.
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Cinobufagin modulates vasculogenic mimicry and tumor-associated macrophages to inhibit ovarian cancer progression.
Eur J Pharmacol
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Key Laboratory of Xin'an Medicine, Anhui Province Key Laboratory of R&D of Chinese Medicine, Ministry of Education, Anhui University of Traditional Chinese Medicine, 103 Meishan Road, Shushan District, Hefei City, Anhui Province, 230038, China; Anhui Academy of Traditional Chinese Medicine Bozhou Branch, Bozhou City, Anhui Province, 236800, China. Electronic address:
Background: Ovarian cancer is among the most prevalent malignant tumors affecting women. While conventional therapies like surgery do provide some measure of disease control, they are accompanied by evident side effects that may readily result in drug resistance. Cinobufagin (HCS) is a water-soluble active component extracted from the dried skin of the Bufo gargarizans.
View Article and Find Full Text PDFFantastic Frogs and Where to Use Them: Unveiling the Hidden Cinobufagin's Promise in Combating Lung Cancer Development and Progression Through a Systematic Review of Preclinical Evidence.
Cancers (Basel)
November 2024
Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, SP, Brazil.
Article Synopsis
- Cinobufagin (CB) is a promising anticancer agent for lung cancer, showing potential through various preclinical studies that highlight its ability to inhibit tumor growth and promote cell death.
- The review analyzed data from both lab-based (in vitro) and animal (in vivo) studies, finding that CB decreases cell viability while affecting key molecular pathways related to cancer.
- Despite its effectiveness, limitations like the reliance on lab models, variability in study methodologies, and a lack of long-term safety data suggest more clinical trials are needed to confirm CB's safety and efficacy in humans.
Cinobufagin Suppresses Lipid Peroxidation and Inflammation in Osteoporotic Mice by Promoting the Delivery of miR-3102-5p by Macrophage-Derived Exosomes.
Int J Nanomedicine
October 2024
Shi's Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
Article Synopsis
- Cinobufagin, a compound from toad venom, shows potential in protecting bone health, particularly against osteoporosis, by increasing bone density and mass.
- The study involved testing cinobufagin and its exosomes on ovariectomized mice, revealing significant improvements in bone metrics and reductions in inflammation and oxidative stress.
- Findings suggest that cinobufagin enhances the function of macrophage-derived exosomes, which deliver miR-3102-5p to target the gene alox15, thereby promoting bone formation and inhibiting processes that lead to bone loss.
Cinobufagin inhibits M2‑like tumor‑associated macrophage polarization to attenuate the invasion and migration of lung cancer cells.
Int J Oncol
November 2024
Department of Pathogenic Biology and Immunology, Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, P.R. China.
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- Macrophages play vital roles in immune responses and can change their behavior (polarization) based on their environment, which was studied in relation to the drug cinobufagin (CB).
- The study found that CB impacts the growth of certain tumor cells (A549 and LLC) while leaving normal macrophages and lung epithelial cells largely unaffected at lower doses.
- CB altered the behavior and characteristics of different types of macrophages, influencing inflammatory responses, and ultimately showed promise in reducing tumor growth in conjunction with cisplatin treatment.
Identification of macrophage driver genes in fibrosis caused by different heart diseases based on omics integration.
J Transl Med
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Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, China.
Background: Myocardial fibrosis, a hallmark of heart disease, is closely associated with macrophages, yet the genetic pathophysiology remains incompletely understood. In this study, we utilized integrated single-cell transcriptomics and bulk RNA-seq analysis to investigate the relationship between macrophages and myocardial fibrosis across omics integration.
Methods: We examined and curated existing single-cell data from dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), myocardial infarction (MI), and heart failure (HF), and analyzed the integrated data using cell communication, transcription factor identification, high dimensional weighted gene co-expression network analysis (hdWGCNA), and functional enrichment to elucidate the drivers of macrophage polarization and the macrophage-to-myofibroblast transition (MMT).
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