Tanshinone IIA, an isolated compound from Salvia miltiorrhiza Bunge, induces apoptosis in HeLa cells through mitotic arrest.
OBJECTIVE
Tanshinone IIA (Tan IIA) is a compound isolated from Salvia miltiorrhiza Bunge (Danshen). The aim of this study is to investigate the mechanisms of its anti-cancer effect.


METHODS
To clearly delineate the cell cycle-dependent effects of Tan IIA, we used either synchronized cells or single living cell analysis to conduct our studies. Subcellular fractionation, Western blot analysis, immuno-fluorescence staining and FACS analysis were also employed in our study.


RESULTS
We found that Tan IIA could arrest cancer cells in mitosis by disrupting the mitotic spindle and subsequently triggered cells to enter apoptosis through the mitochondria-dependent apoptotic pathway. Thus, Tan IIA could selectively kill mitotic cells over interphase cells. In comparison with other existing anti-cancer drugs that cause mitotic arrest by interfering with the microtubule structure (such as vincristine or taxol), Tan IIA destroyed only the mitotic spindle during the M phase but not the microtubule structure in interphase cells. Furthermore, Tan IIA could trigger the mitotic arrested cells to enter apoptosis faster than vincristine or taxol.


CONCLUSIONS
Since Tan IIA can selectively induce cancer cells to enter apoptosis through mitotic arrest, it has the potential to be developed into an anti-cancer drug.
Zhou
Lingli
L
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Chan
W K
WK
Xu
Naihan
N
Xiao
Kang
K
Luo
Houwei
H
Luo
Kathy Qian
KQ
Chang
Donald C
DC
D045784:Abietanes; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D045784:Abietanes; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; C021751:tanshinone; D049452:Green Fluorescent Proteins; D004247:DNA