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Fiscalin B exerts an anticancer effect through mitochondria-modulated apoptosis and cell cycle arrest in human
Siqi Wang1, Yi Huang1, Songtao Wang2
1Department of Pharmacy, School of Medicine, Jianghan University, Wuhan, China.
Abstract:
Liver cancer remains the leading cause of cancer-related deaths; however, current therapeutic drugs are largely ineffective. This study aimed to investigate the anticancer activity of fiscalin B, a compound extracted from marine fungi, against HepG2 cells and further explore the underlying mechanisms. Our findings revealed that fiscalin B treatment produced overloaded reactive oxygen species (ROS) and induced apoptosis in HepG2 cells, further disrupt the mitochondrial membrane potential, inducing mitochondrial dysfunction. Fluorescence microscopy revealed alterations in the distribution of TOM20 and activation of lysosomes in fiscalin B-treated HepG2 cells. The disruption of mitochondria following fiscalin B treatment marked an improved mitophagy. Moreover, fiscalin B induced G0/G1 cell cycle arrest in HepG2 cells by increasing the phosphorylation of p70S6K and S6, thus affecting the expression of key cell cycle regulators. Overall, fiscalin B exerts an anticancer effect by inducing mitochondria-modulated autophagic cell death and cell cycle arrest in hepatocellular carcinoma (HCC) cells.
Insights
Fiscalin B, a marine fungal compound, shows anticancer effects against liver cancer cells by inducing cell death and halting cell cycle progression. This compound triggers reactive oxygen species overload and mitochondrial dysfunction, leading to autophagic cell death.
Area of Science:
- Marine Natural Products
- Cancer Biology
- Cellular Mechanisms
Background:
- Liver cancer (hepatocellular carcinoma) is a leading cause of cancer mortality with limited effective therapies.
- Marine fungi represent a promising source of novel bioactive compounds for drug discovery.
Purpose of the Study:
- To investigate the anticancer activity of fiscalin B, a marine fungal compound, against human liver cancer cells (HepG2).
- To elucidate the underlying mechanisms of fiscalin B's anti-cancer effects.
Main Methods:
- Treatment of HepG2 cells with fiscalin B.
- Assessment of reactive oxygen species (ROS) levels.
- Analysis of apoptosis, mitochondrial membrane potential, and mitochondrial dysfunction.
- Fluorescence microscopy to observe TOM20 distribution and lysosome activation.
- Evaluation of mitophagy, cell cycle distribution, and key cell cycle regulators.
Main Results:
- Fiscalin B induced significant ROS overload and apoptosis in HepG2 cells.
- Mitochondrial membrane potential was disrupted, indicating mitochondrial dysfunction and enhanced mitophagy.
- Fiscalin B treatment led to G0/G1 cell cycle arrest by modulating key cell cycle regulators.
- Alterations in TOM20 distribution and lysosome activation were observed.
Conclusions:
- Fiscalin B exhibits potent anticancer effects against hepatocellular carcinoma cells.
- The compound induces mitochondria-modulated autophagic cell death and cell cycle arrest.
- Fiscalin B represents a potential therapeutic candidate for liver cancer treatment.
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