The methylene chloride fraction of Trichosanthis Fructus induces apoptosis in U937 cells through the mitochondrial pathway.
Trichosanthis kirilowii MAXIM has been used as a folk remedy to treat diabetes, leukemia, and breast cancer. In the present study, the apoptotic mechanism of the methylene chloride fraction of Trichosanthis Fructus (MCTF) was investigated in human leukemic U937 cells. MCTF exhibited antiproliferative effectsagainst U937 cells (IC50=ca. 8 microg/ml). Apoptotic bodies were observed in MCTF-treated U937 cells in the TUNEL assay. We also confirmed that MCTF significantly increases annexin V(+)/propidium iodide-cells using FACS analysis. MCTF treatment activated caspase-8, -9 and -3, and led to cleaved poly (ADP-ribose) polymerase and release of cytochrome c into cytosol in a concentration-dependent manner, while MCTF did not affect Bax or Bcl-2 protein levels as shown by Western blot analysis. Taken together, these results indicate that MCTF can induce apoptosis in U937 cells chiefly via a mitochondrial-mediated pathway and suggest that Trichosanthis Fructus can be used in cancer treatment as a chemopreventive agent.
Lee
Eun-Ok
EO
Department of Oncology, Graduate School of East-West Medical Science, Yongin, Republic of Korea.
Lee
Ju-Ryoung
JR
Kim
Kwan-Hyun
KH
Baek
Nam-In
NI
Lee
Soo-Jin
SJ
Lee
Bog-Hieu
BH
Cho
Kyung-Dong
KD
Ahn
Kyoo-Seok
KS
Kim
Sung-Hoon
SH
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002855:Chromatography, Thin Layer; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007723:Korea; D008752:Methylene Chloride / Q000737:chemistry*; D008928:Mitochondria / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D010944:Plants / Q000737:chemistry*; D012997:Solvents; D020298:U937 Cells
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012997:Solvents; D008752:Methylene Chloride; D045304:Cytochromes c