Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells.
Crude extract of Scutellaria baicalensis (S. baicalensis) has cytotoxic effect on human myelogenous leukemia cells (HL-60). We invesigated which compound from the crude extract is responsible for the cytotoxic effect on HL-60 cells. We identified 29 compounds from the crude extract using high performance liquid chromatography mass spectrometry (HPLC/MS). Two of the compounds, baicalin and wogonoside, are converted to baicalein and wogonin, respectively, after treatment with beta-glucuronidase. We observed a dose-dependent reduction in cell viability when cells with either wogonin or aqueous extract of S. baicalensis. Several of the apoptotic features including deoxyribonucleic acid (DNA) fragmentation and increased caspase-3 activity were found in cells treated with wogonin and aqueous extract. The changes were associated with down-regulation of Bcl-2, and not Bax. Furthermore, treatment of HL-60 cells with wogonin or S. baicalensis led to the inhibition of human telomerase reverse transcriptase (hTERT), human telomerase-associated protein 1 (hTP1) and c-myc messenger ribonucleic acid (m-RNA) expression. Wogonin and S. baicaleisis down-regulated the telomerase activity. Our findings suggest that wogonin may be the major compound in S. baicalensis responsible for HL-60 growth inhibition in vitro. The inhibition of HL-60 cell growth is mediated partly through the induction of Bax/Bcl-2 apoptosis and by telomerase inhibition through suppression of c-myc, which is a promoter of hTERT.
Huang
Sheng-Teng
ST
Department of Chinese Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan. shenteng@adm.cgmh.org.tw
Wang
Chen-Yu
CY
Yang
Rong-Chi
RC
Chu
Chih-Ju
CJ
Wu
Hsiao-Ting
HT
Pang
Jong-Hwei S
JH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D031364:Scutellaria baicalensis / Q000737:chemistry; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D044950:Flavanones; C116115:MYCBP protein, human; D026901:Membrane Transport Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; C103676:SEC62 protein, human; C499814:Scutellaria baicalensis extract; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D019098:Telomerase; C085514:wogonin