A botanical extract from channel flow inhibits cell proliferation, induces apoptosis, and suppresses CCL5 in human endometriotic stromal cells.
Growing evidence suggests that medicinal herbs have direct actions on endometrial cells. By screening multiple herbs using an in vitro model of endometriosis, we found that a commonly used herbal formula exerted considerable antiproliferative effects. Our purpose was to investigate the effects of this antiendometriosis herbal mixture on cell proliferation, apoptosis, and CCL5 expression and secretion in endometriotic stromal cells in vitro. Isolated normal endometrial, eutopic, and ectopic endometriotic stromal cells were cultured under established conditions. Cell proliferation, apoptosis, and CCL5 gene expression protein secretion was evaluated after incubation with different concentrations of an antiendometriosis herbal mixture extract. Cell proliferation was assessed by cell counting, (3)H-thymidine incorporation, and MTS assays. Apoptosis was determined by blotting using anti-cleaved caspase 3 antibodies and by a TUNEL assay. CCL5 gene expression and protein secretion were determined by transient transfection of gene promoter reporters and ELISAs in cell supernatants. Extracts of a traditional herbal mixture dose-dependently decreased cell proliferation in normal, eutopic, and ectopic endometriotic stromal cells. (3)H-Thymidine uptake and MTS confirmed these findings. The herbal extracts induced apoptosis, as evidenced by activation of caspase 3 and the presence of TUNEL-positive cells after treatment. The herbal extracts also suppressed CCL5 gene transcription and protein secretion in endometriotic stromal cells, even when corrected for cell number. Extracts from a medicinal herbal mixture have direct effects on cell proliferation, apoptosis, and CCL5 production in endometriotic stromal cells. Our findings support the further investigation of novel, potentially safe and well-tolerated botanical products as future endometriosis treatments.
Wieser
Fritz
F
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA. fwieser@emory.edu
Yu
Jie
J
Park
John
J
Gaeddert
Andrew
A
Cohen
Misha
M
Vigne
Jean-Louis
JL
Taylor
Robert N
RN
D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004715:Endometriosis / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D019684:Magnoliopsida / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000378:metabolism; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014162:Transfection; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D004365:Drugs, Chinese Herbal; D048069:Tumor Necrosis Factors; D053148:Caspase 3