BZL101, a phytochemical extract from the Scutellaria barbata plant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype.
BZL101 is an aqueous extract from the Scutellaria barbata plant shown to have anticancer properties in a variety of human cancers. In order to determine its efficacy on human reproductive cancers, we assessed the responses of two human breast cancer cell lines, estrogen sensitive MCF7 and estrogen insensitive MDA-MB-231, and of two human prostate cancer cell lines, androgen sensitive LNCaP and androgen insensitive PC3 which are human cell lines that represent early and late stage reproductive cancers. BZL101 inhibited reproductive cancer growth in all cell lines by regulating expression levels of key cell cycle components that differ with respect to the cancer cell phenotypes. In early stage estrogen sensitive MCF7 cells, BZL101 induced a G₁ cell cycle arrest and ablated expression of key G₁ cell cycle regulators Cyclin D1, CDK2 and CDK4, as well as growth factor stimulatory pathways and estrogen receptor-α expression. Transfection of luciferase reporter plasmids revealed that the loss of CDK2, CDK4 and estrogen receptor-α transcript expression resulted from the BZL-dependent ablation of promoter activities. BZL101 growth arrests early stage androgen sensitive LNCaP cells in the G₂/M phase with corresponding decreases in Cyclin B1, CDK1 and androgen receptor expression. In late stage hormone insensitive breast (MDA-MB-231) and prostate (PC3) cancer cells, BZL101 induced an S phase arrest with corresponding ablations in Cyclin A2 and CDK2 expression. Our results demonstrate that BZL101 exerts phenotype specific anti-proliferative gene expression responses in human breast and prostate cancer cells, which will be valuable in the potential development of BZL-based therapeutic strategies for human reproductive cancers.
Marconett
Crystal N
CN
Department of Molecular and Cell Biology, University of California at Berkeley, USA.
Morgenstern
Travis J
TJ
San Roman
Adrianna K
AK
Sundar
Shyam N
SN
Singhal
Ankur K
AK
Firestone
Gary L
GL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056751:Cyclin A2 / Q000235:genetics; D056744:Cyclin B1 / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D031363:Scutellaria
D000972:Antineoplastic Agents, Phytogenic; D056751:Cyclin A2; D056744:Cyclin B1; D010936:Plant Extracts; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; C524947:Scutellaria barbata extract; D019938:Cyclin D1; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4