Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells.
We previously demonstrated that combined treatment with extracts of the medicinal mushroom Ganoderma lucidum and the herb Duchesnea chrysantha (GDE) significantly suppresses cell growth and selectively induces apoptosis in human leukemia HL-60 cells, but not in normal cells. GDE?s mechanism of action and its activity against HL-60 cells suggest that it could be suitable for the combined-modality treatment of hematological malignancies. In the present study, we examined whether treatment with a combination of GDE and ionizing radiation enhances the therapeutic effect. We demonstrated that, when used in combination with radiation at a clinically relevant dose of 2 Gy, GDE further suppressed cell proliferation and induced apoptosis as well as micronuclei formation in HL-60 cells, leading to increased cell death. Furthermore, GDE pretreatment not only reduced radiation-induced G2/M-phase arrest, but also induced G1-phase arrest. These events are associated with the inhibition of cyclin-dependent kinase 1 (CDK1) phosphorylation and the dephosphorylation of retinoblastoma protein (pRB). Collectively, these data show that combined treatment with GDE and radiation enhances radiation-induced apoptosis and overall cell death. These findings may be clinically relevant and suggest a novel therapeutic strategy for increasing the efficacy of radiotherapy.
Kim
Kug Chan
KC
Department of Radiation Biology, Nuclear Environmental Safety Research Center, Korea Atomic Energy Research Institute, Daejeon 305-353, Korea.
Jun
Hyun Jeong
HJ
Kim
Jin Sik
JS
Kim
In Gyu
IG
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000627:therapeutic use; D018922:HL-60 Cells; D006801:Humans; D015162:Micronucleus Tests; D008928:Mitochondria / Q000187:drug effects / Q000528:radiation effects; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D020940:Reishi; D016160:Retinoblastoma Protein / Q000378:metabolism; D027824:Rosaceae
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011838:Radiation-Sensitizing Agents; D016160:Retinoblastoma Protein; D016203:CDC2 Protein Kinase; C505407:CASP3 protein, human; D053148:Caspase 3