Asiatic acid induces colon cancer cell growth inhibition and apoptosis through mitochondrial death cascade

Cancer is one of the leading causes of death in the world. The triterpenoid compound asiatic acid derived from the tropical medicinal plant Centella asiatica displays cytotoxic activity on fibroblast cells and several other kinds of cells. The present work studies asiatic acid-mediated growth inhibi...

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Veröffentlicht in:Biological & pharmaceutical bulletin Jg. 32; H. 8; S. 1399
Hauptverfasser: Tang, Xue-Lian, Yang, Xin-Ying, Jung, Hyun-Ju, Kim, Sung-Yeon, Jung, Suk-Yul, Choi, Du-Young, Park, Won-Cheol, Park, Hyun
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Japan 01.08.2009
Schlagworte:
Animals
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - isolation & purification
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Blotting, Western
Caspase 3 - metabolism
Caspase 9 - metabolism
Cell Cycle - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Centella - chemistry
Chromatin - metabolism
Colonic Neoplasms - pathology
Colorectal Neoplasms - pathology
Cytochromes c - metabolism
DNA Fragmentation - drug effects
Flow Cytometry
Humans
Membrane Potential, Mitochondrial - drug effects
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Microscopy, Fluorescence
Mitochondria - drug effects
Molecular Structure
Pentacyclic Triterpenes
Poly Adenosine Diphosphate Ribose - metabolism
Stomach Neoplasms - pathology
Triterpenes - chemistry
Triterpenes - isolation & purification
Triterpenes - pharmacology
ISSN:1347-5215, 1347-5215
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Zusammenfassung:Cancer is one of the leading causes of death in the world. The triterpenoid compound asiatic acid derived from the tropical medicinal plant Centella asiatica displays cytotoxic activity on fibroblast cells and several other kinds of cells. The present work studies asiatic acid-mediated growth inhibition of cancer cells and the underlying mechanism. Asiatic acid markedly inhibited cancer cell proliferation. Apoptosis of SW480 human colon cancer cells was induced by asiatic acid as shown by flow cytometry, DNA fragmentation and nuclear chromatin condensation experiments. Through increasing mitochondrial membrane permeability and cytochrome c release from mitochondria into cytosol, asiatic acid induced caspase-9 activity, which further activated caspase-3 and poly(ADP-ribose) polymerase cleavage resulting in irreversible apoptotic death in the tumor cells. Taken together, these results suggest that mitochondrial death apoptosis cascade plays very important roles in asiatic acid-induced cancer apoptosis.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1347-5215
1347-5215
DOI:10.1248/bpb.32.1399