The phytochemical Sanguinarine from Sanguinaria canadensis shows promise in fighting liver cancer
Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 16, 2024 1 month, 3 weeks, 1 day, 23 hours, 43 minutes ago
Herbs And Phytochemicals: A new study has shed light on the potential of sanguinarine, a natural compound derived from the bloodroot plant, in combating hepatocellular carcinoma (HCC), the most common type of liver cancer.
The phytochemical Sanguinarine from Sanguinaria canadensis shows promise in fighting liver cancer
Researchers from several prominent institutions in China have discovered that sanguinarine can induce a form of cell death known as necroptosis in HCC cells, offering a new avenue for cancer therapy. This
Herbs And Phytochemicals news report delves into the key findings of the study and explores the mechanisms behind sanguinarine’s anti-cancer effects.
What is Sanguinarine?
Sanguinarine is a bioactive compound extracted from the roots of the Sanguinaria canadensis plant. It has been recognized for its anti-tumor properties across various cancer types. However, its specific mechanisms, particularly in liver cancer, have remained unclear until now. This study, involving researchers from Nanjing Medical University, Tongji University, Shanghai Jiao Tong University, Gongli Hospital, and Shanghai University of Traditional Chinese Medicine, aimed to uncover how sanguinarine affects cancer cell metabolism and induces cell death.
Energy Metabolism in Cancer Cells
Cancer cells, including those in HCC, often exhibit abnormal metabolism to meet their heightened energy demands. This is known as the Warburg effect, where cancer cells rely heavily on aerobic glycolysis over oxidative phosphorylation for energy production. A key player in this process is pyruvate kinase M2 (PKM2), an enzyme involved in glycolysis that is upregulated in many cancers. The study reveals that sanguinarine targets PKM2, disrupting the cancer cells’ energy metabolism and leading to necroptosis.
Study Methods and Key Findings
The researchers used various methods to investigate the effects of sanguinarine on HCC cells, including cell viability assays, western blotting, molecular docking, and animal models. Here are the key findings:
-Inhibition of Cell Proliferation and Metastasis: Sanguinarine significantly inhibited the proliferation and metastasis of HCC cells. In vitro experiments showed reduced colony formation and changes in cell morphology indicative of cell death.
-Induction of Necroptosis: This article highlights that sanguinarine induced necroptosis, a regulated form of cell death different from apoptosis. The researchers observed increased levels of necroptosis markers, such as phosphorylated RIP3 (pRIP3) and MLKL (pMLKL), in treated cells.
-Targeting PKM2: Transcriptome sequencing identified PKM2 as a significant target of sanguinarine. Molecular docking studies further confirmed a strong binding affinity between sanguinarine and PKM2, inhibiting its activity and disrupting glycolysis.
ng>-Reduction in Aerobic Glycolysis: Sanguinarine-treated cells showed decreased lactate production and glucose uptake, indicating a reduction in glycolysis. Protein levels of key glycolytic enzymes were also reduced.
-Mitochondrial Dysfunction: Sanguinarine disrupted mitochondrial structure and function, leading to increased reactive oxygen species (ROS) production, mitochondrial membrane potential depolarization, and excessive opening of mitochondrial permeability transition pores (MPTP).
-Impact on PKM2/β-Catenin Axis: Sanguinarine inhibited the translocation of PKM2 into the nucleus and reduced the interaction between PKM2 and β-catenin. This disruption affected the transcriptional activity of PKM2/β-catenin signaling and its downstream genes, such as cyclin D1 and c-Myc.
In Vivo Evidence
The study extended its findings to animal models to validate the effects of sanguinarine in a physiological context. Mice treated with sanguinarine showed reduced tumor nodules and decreased levels of PKM2 and β-catenin in liver tissues. Histological analysis revealed less neoplastic clustering and a more organized hepatic structure in treated mice compared to controls.
Potential Clinical Implications
The promising results from this study suggest that sanguinarine could be developed as a therapeutic agent for HCC. By targeting PKM2 and disrupting cancer cell metabolism, sanguinarine induces necroptosis, which could overcome the resistance often seen with traditional apoptosis-inducing therapies.
Conclusion
This study provides substantial evidence supporting the anti-tumor potential of sanguinarine in hepatocellular carcinoma. By inducing necroptosis and targeting the PKM2/β-catenin axis, sanguinarine disrupts the metabolic processes essential for cancer cell survival and proliferation. Further research and clinical trials are necessary to explore the full potential of sanguinarine as a cancer therapy.
The study findings were published in the peer-reviewed journal: Cancers.
https://www.mdpi.com/2072-6694/16/14/2533
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