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Published on: October 30, 2013
Cantharidin induces apoptosis in human bladder cancer TSGH 8301 cells through mitochondria-dependent signal pathways
Jehn-Hwa Kuo1, Yung-Lin Chu, Jai-Sing Yang
1Special Class of Healthcare, Industry Management, Central Taiwan University of Science and Technology, Taichung, Taiwan, ROC.
Abstract:
Cantharidin has shown potent anticancer activities on many types of human cancer cells. This study was performed to elucidate whether mitochondria and caspases are involved in the modulation of apoptosis and cell cycle arrest by cantharidin in human bladder cancer cells. The effect of cantharidin on cell cycle arrest, apoptosis, caspases, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨ(m)) were measured by flow cytometry, and the levels of apoptosis-associated proteins and its regulatory molecules were studied by Western blotting. Cantharidin-induced apoptosis and DNA damage was determined by flow cytometric analysis, DAPI staining and Comet assay. After cantharidin treatment, the active forms of caspase-3, -8 and -9 were promoted. Cantharidin-induced apoptosis was associated with enhanced ROS and Ca(2+) generations, caused DNA damage, decreased the levels of ΔΨ(m) and promoted Endo G and AIF released from mitochondria. Cantharidin-induced G0/G1 arrest was associated with a marked decrease in the protein expressions of cyclin E and Cdc25c but promoted the levels of p21 and p-p53. Cantharidin-induced apoptosis was accompanied with up-regulation of the protein expression of Bax and PARP, but down-regulation of the protein levels of Bcl-2, resulting in dysfunction of mitochondria then led to Endo G and AIF release for causing induction of apoptosis.
Insights
Cantharidin induces apoptosis and cell cycle arrest in human bladder cancer cells by activating caspases and generating reactive oxygen species (ROS). This natural compound disrupts mitochondrial function, leading to DNA damage and programmed cell death.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- Cantharidin exhibits significant anticancer properties against various human cancer cell lines.
- Understanding the molecular mechanisms underlying cantharidin's effects is crucial for its therapeutic development.
Purpose of the Study:
- To investigate the role of mitochondria and caspases in cantharidin-induced apoptosis and cell cycle arrest in human bladder cancer cells.
- To elucidate the signaling pathways involved in cantharidin's cytotoxic effects.
Main Methods:
- Flow cytometry was used to assess cell cycle arrest, apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (ΔΨ(m)).
- Western blotting analyzed apoptosis-associated proteins and regulatory molecules.
- DNA damage was evaluated using DAPI staining and Comet assay.
Main Results:
- Cantharidin treatment promoted active caspase-3, -8, and -9, indicating caspase activation.
- Apoptosis was linked to increased ROS and Ca(2+) levels, DNA damage, decreased ΔΨ(m), and release of Endonuclease G (Endo G) and apoptosis-inducing factor (AIF) from mitochondria.
- Cantharidin induced G0/G1 cell cycle arrest by altering the expression of cyclins (e.g., cyclin E, Cdc25c) and cell cycle regulators (p21, p-p53).
- Upregulation of Bax and PARP, alongside downregulation of Bcl-2, contributed to mitochondrial dysfunction and apoptosis.
Conclusions:
- Cantharidin effectively induces apoptosis and G0/G1 cell cycle arrest in human bladder cancer cells.
- Mitochondrial dysfunction, caspase activation, and ROS generation are key mechanisms mediating cantharidin's anticancer effects.
- The study highlights cantharidin as a potential therapeutic agent for bladder cancer, warranting further investigation.
