Identification of a potent herbal molecule for the treatment of breast cancer.
BACKGROUND
Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.


METHODS
To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.


RESULTS
PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-kappaB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER+ and ER- BCa cells.


CONCLUSIONS
These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.
Koduru
Srinivas
S
Department of Clinical Sciences, College of Health Sciences, University of Kentucky, Lexington, KY 40536, USA. srinivas.koduru@uky.edu
Sowmyalakshmi
Srinivasan
S
Kumar
Raj
R
Gomathinayagam
Rohini
R
Rohr
Jürgen
J
Damodaran
Chendil
C
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D010936:Plant Extracts; D011960:Receptors, Estrogen