Parthenolide suppresses tumor growth in a xenograft model of colorectal cancer cells by inducing mitochondrial dysfunction and apoptosis.
Parthenolide (PT), a principal active component in medicinal plants, has been used conventionally to treat migraine and inflammation. This component has recently been reported to induce apoptosis in cancer cells, through mitochondrial dysfunction. In the present study, we investigated PT-mediated cell death signaling pathway by focusing on the involvement of Bcl-2 family members in human colorectal cancer cells. We also investigated the inhibitory effect of PT on tumor growth in xenografts. Using the human colorectal cancer cell lines HT-29, SW620 and LS174T, we demonstrated that treatment of these cancer cells with PT induces apoptosis using MTT, Annexin V assay and Hoechst 33258 staining. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, cytochrome c release and caspase activation. Moreover, intraperitoneal injection of PT showed significant inhibition of tumor growth, angiogenesis in the xenograft model. These results demonstrate that PT exhibits anti-cancer activity in human colorectal cancer in vitro and in vivo. These findings may also provide a novel approach for the treatment of colorectal cancer.
Department of Internal Medicine and Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University, Jeonju 561-712, Republic of Korea.
Se-Lim
SL
Kim
Kieu The Thu
KT
Trang
Seong Hun
SH
Kim
In Hee
IH
Kim
Seung Ok
SO
Lee
Soo Teik
ST
Lee
Dae Ghon
DG
Kim
Sang-Wook
SW
Kim
D017209:Apoptosis / Q000187:drug effects*; D063646:Carcinogenesis / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D019254:Genes, bcl-2 / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D012717:Sesquiterpenes; C002669:parthenolide; D045304:Cytochromes c