Abstract

Title : ANTIPROLIFERATIVE AND CYTOTOXIC ACTIVITY ON GLIOBLASTOMA MULTIFORME (GBM) T98G CELL LINE OF HYDROXYCHAVICOL ISOLATED FROM Piper betel Linn. LEAVES
By : CHUTPONG CHOOTO AND THIPPAWON CHOTPANITSETH
Degree : DOCTOR OF PHARMACY
Advisor : ASST. PROF. PAJAREE TONGNGOK, Ph.D AND KUSUMA JITSAENG, Ph.D
Keywords : GLIOBLASTOMA MULTIFORME, CYTOTOXIC ACTIVITY, HYDROXYCHAVICOL, Piper betle L.
   
Glioblastoma multiforme (GBM) is a disease of the brain tumors or malignant brain cancer and it is the highest grade and the most malignant form of glioblastoma. This is because tumor cells are highly proliferative, poorly differentiated, and greatly invasive into the surrounding tissues. The treatments of most high-grade glioblastoma with selective surgery, radiotherapy, and chemotherapy are often found a recurrence, leading to a poor prognosis and low survival rate in patients. Therefore, the discovery of novel anti-cancer agents has been considerably progressed. Piper betel L. is a vine widely grown medicinal plants and it was traditionally used as herbal medicine for dermal irritation and fungal infection. Several studies revealed that P. betel extracts, especially hydroxychavicol, have antioxidant, antimicrobial, and antimutagenic activities. Objectives= The aims of this study are to isolate the active phenolic compound namely hydroxychavicol from the leaves of P. betel and to investigate the effect of hydroxychavicol on cell viability of human GBM T98G cell line as compared to vehicle-treated controls. Method= To isolated and purify hydroxychavicol, dried P. betel leaves were macerated and filtered with n-hexane and CH2Cl2, respectively. The CH2Cl2. extract was subsequently isolated on silica-columns. To identify hydroxychavicol, the thin layer chromatography (TLC) pattern profiles of some selected fractions were compared to the pattern of previously purified compound. Then, various concentrations of this isolated hydroxychavicol were tested for its cytotoxic activity on T98G cell line using PrestoBlue cell viability assay. Results= A pure compound of hydroxychavicol was isolated from P. betel leaves by means of chromatographic techniques. In addition, it was found that hydroxychavicol at concentration of 500 µM significantly reduced the relative percentage of T98G viable cells to only 52.63 after 24 hour of treatment (p < 0.05). This is significantly relative to the group of control and cells treated with various concentrations of hydroxychavicol (p < 0.05). In fact, administration of hydroxychavicol at concentrations of 50, 100, 150, and 300 µM decreased the relative percentage of T98G viable cells to 90.89, 90.90, 97.68, and 83.71, respectively. Conclusions= This study shows that hydroxychavicol is isolated and purified from P. betel leaves and it has cytotoxic activity on tested T98G cell line. Therefore, further study should be conducted to elucidate its underlying mechanisms of action and ultimately develop to be an anti-cancer therapeutic agent.
   
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