Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition.

Abstract

BACKGROUND:

Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis.

METHODOLOGY:

BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancer cells was assayed.

PRINCIPAL FINDINGS:

Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells.

CONCLUSIONS:

Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.

• Authors: Zhen Liu, Biao Zhang, Kun Liu, Zonghui Ding, Xun Hu
• Journal: PloS one (PLoS One) Vol. 7 Issue 7 Pg. e40480 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22848381 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cyclooctanes
• Lignans
• Polycyclic Compounds
• schizandrin A

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Bone Neoplasms (drug therapy, pathology, secondary)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cyclooctanes (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Humans
• Lignans (pharmacology)
• Lung Neoplasms (drug therapy, pathology, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Neoplasm Transplantation
• Polycyclic Compounds (pharmacology)
• Transplantation, Heterologous
• Xenograft Model Antitumor Assays