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Cytotoxic Components Against Human Oral Squamous Cell Carcinoma Isolated from Andrographis paniculata
Ryuichiro Suzuki1, Yasuaki Matsushima1, Noriyuki Okudaira2
1Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
Background:
The 5-year survival rate of patients with oral cancer has remained approximately 50% during the past 30 years, possibly due to the poor tumor selectivity of conventional anticancer drugs. This prompted us to search for new candidates for anticancer drugs that have higher cytotoxicity and tumor selectivity.
Materials And Methods:
Dried leaves of Andrographis paniculata were supplied from a market in Shanghai. The methanolic fraction of A. paniculata was further fractionated to identify cytotoxic principles by spectroscopic analysis and comparison with literature values. Viable cell number was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method, and tumor specificity was calculated by relative cytotoxicity against oral squamous cell carcinoma cell lines compared to that against normal oral cells. Apoptosis induction was detected by cleaved poly (ADP-ribose) polymerase and caspase-3 on western blot analysis.
Results:
Major cytotoxicity in the methanol extract of a leaf of A. paniculata was recovered by partitioning with EtOAc, followed by silica gel chromatography. Further purification with reversed-phase high-performance liquid chromatography led to isolation of four known cytotoxic compounds, 14-deoxyandrographolide, andrographolide, neoandrographolide and deoxyandrographiside. Among them, andrographolide had the greatest cytotoxicity and tumor specificity, also inducing caspase-3 activation of HSC-2 oral squamous cell carcinoma cells.
Conclusion:
The present study identified andrographolide as a major antitumor principle in the methanolic extract of leaves of A. paniculata.
Insights
Researchers identified andrographolide from Andrographis paniculata leaves as a potent anticancer compound. This natural product shows high cytotoxicity and tumor selectivity against oral cancer cells.
Area of Science:
- Phytochemistry
- Pharmacology
- Oncology
Background:
- Oral cancer survival rates remain stagnant at approximately 50% over 30 years.
- Conventional anticancer drugs exhibit poor tumor selectivity, limiting efficacy.
- There is a critical need for novel anticancer agents with enhanced cytotoxicity and tumor specificity.
Purpose of the Study:
- To identify and isolate cytotoxic compounds from Andrographis paniculata leaves.
- To evaluate the tumor selectivity and apoptotic effects of isolated compounds against oral cancer.
Main Methods:
- Methanolic extraction and fractionation of Andrographis paniculata leaves.
- Silica gel chromatography and reversed-phase high-performance liquid chromatography for compound isolation.
- Cytotoxicity assays (MTT) and apoptosis detection (Western blot for cleaved PARP and caspase-3).
Main Results:
- Four known cytotoxic compounds were isolated: 14-deoxyandrographolide, andrographolide, neoandrographolide, and deoxyandrographiside.
- Andrographolide demonstrated the highest cytotoxicity and tumor selectivity against oral squamous cell carcinoma cells.
- Andrographolide induced caspase-3 activation in HSC-2 oral cancer cells, indicating apoptosis.
Conclusions:
- Andrographolide is identified as a major antitumor principle from Andrographis paniculata leaves.
- The findings suggest andrographolide's potential as a targeted therapy for oral cancer.
- Further research into andrographolide's mechanism of action and clinical application is warranted.
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