Characterisation of Plant Derived Damnacanthal and Nordamnacantbal Induced Cytotoxicity on Human HT29 Colon Adenocarcinoma Cell Line
Nordamnacanthal and damnacanthal are two anthraquinones isolated from the roots of Morinda elliptica. They were found to exhibit cytotoxic activity against HT29 human colon adenocarcinoma cells. The cytotoxic concentrations of damnacanthal and nordamnacanthal that inhibited 50% growth (IC₅₀) of H...
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| Format: | Thesis |
| Language: | English English |
| Published: |
2001
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/8460/1/FSMB_2001_36_IR.pdf http://psasir.upm.edu.my/id/eprint/8460/ |
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| Institution: | Universiti Putra Malaysia |
| Language: | English English |
| Summary: | Nordamnacanthal and damnacanthal are two anthraquinones isolated from the roots of
Morinda elliptica. They were found to exhibit cytotoxic activity against HT29 human
colon adenocarcinoma cells. The cytotoxic concentrations of damnacanthal and
nordamnacanthal that inhibited 50% growth (IC₅₀) of HT29 were 17 µg/ml and 7 µg/ml respectively. For the comparative purposes, the ICsos of several cytotoxic drugs
against HT29 were also determined. The inhibition effect of nordamnacanthal was
found to be comparable to etoposide (IC₅₀ = 7 µg/ml). cisplatin (IC₅₀ = 5 µg/ml) and
doxorubicin (IC₅₀ = 6 µg/ml). The compound was found to be less active than
methotrexate (MTX) (IC₅₀ < 0.05 µg/ml) and leunase (IC₅₀ = 2 µg/ml). On the other
hand, the cytotoxic effect of damnacanthal was less active as compared to all cytotoxic
drugs. However both compounds were found to be less toxic against non-cancerous
fibroblast 3T3 ceJJs with the ICsos of 30 /lglml (damnacanthal) and 21 /lglm]
(nordamnacanthal) respectively. Furthermore, damnacanthal and nordamnacanthal
were found to induce apoptosis on HT29 cells at their ICso concentration as demonstrated by conventional agarose gel electrophoresis and also morphological
alterations. DNA laddering was obtained after 12 hours of treatment by both
compounds in a dose-independent but time-dependent fashion. Both compounds also
caused cell death with apoptotic features such as cell shrinkage, membrane blebbing,
nuclear fragmentation, and the presence of apoptotic bodies. In addition, caspase-3
was found to be activated during the execution of apoptosis induced by these
compounds. This caspase activation was inhibited by a peptide based general caspase
inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-V AD-FMK).
In conclusion, this study demonstrates the potential antitumor activites of
damnacanthal and nordamnacanthal. |
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