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 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.
Tang
Xue-Lian
XL
Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk, South Korea.
Yang
Xin-Ying
XY
Jung
Hyun-Ju
HJ
Kim
Sung-Yeon
SY
Jung
Suk-Yul
SY
Choi
Du-Young
DY
Park
Won-Cheol
WC
Park
Hyun
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D028041:Centella / Q000737:chemistry; D002843:Chromatin / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D013274:Stomach Neoplasms / Q000473:pathology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D002843:Chromatin; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D011064:Poly Adenosine Diphosphate Ribose; D045304:Cytochromes c; C017032:asiatic acid; D053148:Caspase 3; D053453:Caspase 9