HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells.

Abstract
Phytoestrogen intake is known to be beneficial to decrease breast cancer incidence and progression. But its molecular mechanisms of action are still unknown. The present study aimed to examine the effect of apigenin on proliferation and apoptosis in HER2-expressing breast cancer cells. In our experiments, apigenin inhibited the proliferation of BT-474 cells in a dose- and time-dependent manner. Apigenin also inhibited clonogenic survival (anchorage-dependent and -independent) of BT-474 cells in a dose-dependent manner. These growth inhibitions were accompanied with an increase in sub-G0/G1 apoptotic populations. Apigenin-induced extrinsic a caspase-dependent apoptosis up-regulating the levels of cleaved caspase-8 and cleaved caspase-3, and inducing the cleavage of poly (ADP-ribose) polymerase (PARP). Whereas, apigenin did not induce apoptosis via intrinsic mitochondrial apoptosis pathway since this compound did not decrease mitochondrial membrane potential without affecting the levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX). Apigenin reduced the expression of phospho-JAK1, phospho-JAK2 and phospho-STAT3 and decreased signal transducer and activator of transcription 3 (STAT3) dependent luciferase reporter gene activity in BT-474 cells. Apigenin inhibited CoCl2-induced VEGF secretion and decreased the nuclear translocation of STAT3. Our study indicates that apigenin induces apoptosis through inhibition of STAT3 signalling and could serve as a useful compound to prevent or treat HER2-overexpressing breast cancer.
AuthorsHye-Sook Seo, Jae Kyung Jo, Jin Mo Ku, Han-Seok Choi, Youn Kyung Choi, Jong-Kyu Woo, Hyo In Kim, Soo-Yeon Kang, Kang Min Lee, Koong Won Nam, Namkyu Park, Bo-Hyoung Jang, Yong Cheol Shin, Seong-Gyu Ko
JournalBioscience reports (Biosci Rep) Vol. 35 Issue 6 (Oct 23 2015) ISSN: 1573-4935 [Electronic] England
PMID26500281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 Authors.
Chemical References
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Apigenin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Caspases
Topics
  • Apigenin (administration & dosage)
  • Apoptosis (drug effects)
  • Breast Neoplasms (drug therapy, genetics, pathology)
  • Caspases (genetics)
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Receptor, ErbB-2 (biosynthesis, genetics)
  • STAT3 Transcription Factor (biosynthesis, genetics)
  • Signal Transduction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: