Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells.

Abstract

ETHNOPHARMACOLOGY RELEVANCE:

Oldenlandia diffusa (OD) has long been known as an apoptotic inducer in breast tumors in ethnomedicine.

AIM OF THE STUDY:

To scientifically confirm the anti-breast cancer effects of water, methanol (MeOH) and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)-1 and intracellular signaling in MCF-7 breast cancer cells.

MATERIALS AND METHODS:

MeOH extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their ability to inhibit phorbol myristate acetate (PMA)-induced matrix metalloproteinase (MMP)-9 and intercellular adhesion molecule (ICAM)-1 expressions in MCF-7 human breast cancer cells. Additionally, transwell migration, invasion and transcriptional activity were assessed. Results of immunofluorescence confocal microscopy for translocation of NF-κB and p-ERK and p-p38 were also checked. Finally, apoptotic signals including processed caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined.

RESULTS:

MOD and BOD specifically inhibited PMA-induced MMP-9 expression as well as invasive and migration potential via ICAM-1. The inhibitory activity was also based on the suppressed transcriptional activity in MCF-7 breast cancer cells. Results of immunofluorescence confocal microscopy showed that translocation of NF-κB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD activated apoptosis-linked proteins including enzymatically active forms of processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with increased expression of mitochondrial apoptotic protein, Bax and decreased expression of Bcl-2.

CONCLUSION:

The results indicate that OD as an anti-metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and NF-κB, thus reducing the invasion capacity of MCF-7 breast cancer cells through inhibition of MMP-9 and ICAM-1 expression and plays an important role in the regulation of breast cancer cell apoptosis.

• Authors: Tae-Wook Chung, Hyunju Choi, Ji-Min Lee, Sun-Hyung Ha, Choong-Hwan Kwak, Fukushi Abekura, Jun-Young Park, Young-Chae Chang, Ki-Tae Ha, Seung-Hak Cho, Hyeun Wook Chang, Young-Choon Lee, Cheorl-Ho Kim
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 195 Pg. 309-317 (Jan 04 2017) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 27876502 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Apoptosis Regulatory Proteins
• Butanols
• ICAM1 protein, human
• NF-kappa B
• Plant Extracts
• Water
• Intercellular Adhesion Molecule-1
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Methanol

Topics

• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Breast Neoplasms (drug therapy, enzymology, genetics, pathology)
• Butanols (chemistry)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• MCF-7 Cells
• Matrix Metalloproteinase 9 (metabolism)
• Methanol (chemistry)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Oldenlandia (chemistry)
• Phosphorylation
• Phytotherapy
• Plant Extracts (isolation & purification, pharmacology)
• Plants, Medicinal
• Signal Transduction (drug effects)
• Transcription, Genetic (drug effects)
• Transfection
• Water (chemistry)
• p38 Mitogen-Activated Protein Kinases (metabolism)