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Andrographolide induces apoptosis of C6 glioma cells via the ERK-p53-caspase 7-PARP pathway
Shih-Hung Yang1, Seu-Mei Wang2, Jhih-Pu Syu2
1Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No. 7, Zhongshan South Road, Zhongzheng District, Taipei City 100, Taiwan.
Background:
Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo.
Methods:
Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model.
Results And Conclusion:
In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.
Insights
Andrographolide (AND) effectively combats glioblastoma by inducing cancer cell death and inhibiting tumor growth. This natural compound shows promise as a safe and effective glioma treatment, sparing healthy cells.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Glioma represents a highly malignant primary brain tumor requiring novel therapeutic strategies.
- Andrographolide (AND), derived from Andrographis paniculata, exhibits known antitumor properties.
- The efficacy of AND against glioblastoma remains to be elucidated.
Purpose of the Study:
- To investigate the in vitro and in vivo anticancer effects of Andrographolide (AND) on glioblastoma.
- To elucidate the molecular mechanisms underlying AND's cytotoxic effects.
- To assess the safety profile of AND in non-cancerous cells.
Main Methods:
- In vitro apoptosis assays (flow cytometry, nuclear staining) and western blotting to determine signaling pathways.
- In vivo tumor xenograft mouse model to evaluate the impact of AND on tumor growth.
- Assessment of AND's effects on primary astrocyte cells to determine specificity.
Main Results:
- AND triggered significant apoptosis in glioblastoma cells via the ROS-ERK-P53-caspase 7-PARP pathway.
- In vivo studies demonstrated that AND markedly suppressed tumor progression and induced regression of established tumors.
- AND did not induce apoptosis or activate key signaling proteins (ERK, p53) in primary astrocyte cells.
Conclusions:
- AND exhibits potent anti-glioblastoma activity through a defined molecular pathway.
- AND demonstrates significant therapeutic potential for glioma treatment, with a favorable safety profile in normal brain cells.
- AND warrants further investigation as a potential chemotherapeutic agent for glioma.
