Silibinin induces apoptosis and inhibits proliferation of estrogen receptor (ER)-negative breast carcinoma cells through suppression of nuclear factor kappa B activation.
BACKGROUND
Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various types of liver afflictions. In addition, it has recently been considered broadly as a potential chemopreventive agent against many types of cancers. The current study was designed to evaluate the restrictive effects of pharmacological doses of silibinin on SKBR3, an ErbB2-overexpressed and ER-negative human breast carcinoma cell line.


METHODS
Effect of silibinin on metabolic activity and proliferation of human breast carcinoma (SKBR3) cell line were evaluated by MTT and BrdU assays respectively. Furthermore, the proapoptotic effect of silibinin was investigated using flow cytometry. The NF-κB phosphorylation assay was also used to assess the effect of silibinin on NF-κB activation. The alkalizing effect of silibinin on SKBR3 cell line was evaluated by measuring pH of media of the silibinin-treated cells compared to control.


RESULTS
Our results indicate that silibinin inhibited metabolic activity and cell proliferation of SKBR3 cells in a dose-dependent manner. Moreover, silibinin significantly induced apoptosis in SKBR3 cells. On the other hand, silibinin significantly inhibited activation of NF-κB which is known to be highly active in this cell line. Alkalizing effect of silibinin was also observed.


CONCLUSIONS
The results obtained here indicate that silibinin may be an efficacious therapeutic agent against ER-negative breast carcinomas with high inhibitory effect on NF-κB.
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. shghaffari200@yahoo.com.
Meysam
M
Yousefi
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Seyed H
SH
Ghaffari
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Ali
A
Zekri
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Saeed
S
Hassani
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Kamran
K
Alimoghaddam
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Ardeshir
A
Ghavamzadeh
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016328:NF-kappa B; D012838:Silymarin; D000077385:Silybin