Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway.
Bioactive compounds found in many plant species have been used in Chinese, Unani, and Indian ayurvedic medicine. Accumulative evidences in both in vitro and in vivo studies using berberine demonstrated anti-cancer and anti-inflammatory properties in different cancer cells. In the present study, a putative compound from commercial sample was purified by chromatographic techniques. The structure of the pure compound was confirmed by spectroscopic studies. The purified berberine was tested against breast cancer (MCF-7) and normal human breast epithelial (MCF-12F) cells for 24, 48 and 72 h at various concentrations. Using MTT assay, berberine exhibited a significant cytotoxic effect on the MCF-7 cells (P<0.01) without affecting the breast normal epithelial cell growth at 25 microM concentration. Based on these results, MCF-7 cells were treated with 25 microM berberine for 48 and 72 h for further studies to illustrate induction of apoptosis through cell cycle distribution and DNA fragmentation with agarose gel electrophoresis. Western blotting with treated cells revealed that berberine induces apoptosis in MCF-7 cells through a mitochondria-dependent pathway by increasing levels of cytoplasmic cytochrome c, caspase-9 activity and cleavage of PARP while decreasing levels of Bcl-2. Furthermore, immunoblotting results demonstrated that p53 and p27 were up-regulated suggesting that barberine seems to play a pro-apoptotic role in cancer cells. In conclusion, berberine inhibits the proliferation of MCF-7 breast cancer cells through a mitochondria and caspase dependent apoptotic pathway. It is possible that berberine may serve as a potential naturally occurring compound for breast cancer therapy.
Patil
Jeevitha B
JB
Vegetable and Fruit Improvement Center, Department of Horticulture Sciences, Texas A&M University, College Station, TX 77845-2119, USA.
Kim
Jinhee
J
Jayaprakasha
G K
GK
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D001599:Berberine; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases