Cratoxy formosum leaf extract inhibits proliferation and migration of human breast cancer MCF-7 cells.
In this study we investigated how Cratoxy formosum (CF) leaf extract affects the viability and migration of human breast cancer cells including the mechanism(s) responsible. Our results showed that CF leaf extract strongly induced MCF-7 cell death in a concentration- and time-dependent manner, with IC50values of 85.70±4.52μg/mL and 53.74±3.02μg/mL at 24h and 48h, respectively. Additionally, CF leaf extract potentiated the activity of 4 anticancer drugs with the greatest synergy occurring between CF and 5-FU. CF leaf extract also caused a dose-dependent decrease in colony forming ability with IC50values of 36.37+1.80 μg/mL and cell migration, with IC50values of 43.68±0.86μg/mL. Moreover, CF significantly induced ROS formation, increased caspase 3 activities, and reduced the mitochondrial membrane potential, leading to cancer cell apoptosis and cell death. In addition, the extract inhibited cancer cell migration at 25μg/mL by reducing MMP 2 and MMP 9 protein expression. Moreover, CF leaf extracts strongly decreased expression of the cell cycle regulatory protein Rac1 and downstream protein, cdk6. CF leaf extract significantly stimulated p21 and this correlated with a reduction in cyclin D1 protein levels. In summary, CF leaf extract can inhibit cell proliferation, induce cell apoptosis, and reduce cell migration in the MCF-7 cell line. It could also be beneficial for enhancing the activity of anticancer drugs used to treat breast cancer.
Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand. Electronic address: buranrat@gmail.com.
Benjaporn
B
Buranrat
Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand.
Nootchanat
N
Mairuae
Applied Thai Traditional Medicine, Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand.
Ampa
A
Konsue
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D019938:Cyclin D1; D051361:Cyclin-Dependent Kinase 6; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005472:Fluorouracil
Breast cancer; Cell migration; Cratoxy formosum (CF); Cytoxicity; Matrix metalloproteinases (MMP)