HER2 Support Group Forums - View Single Post - BPH-715 (revised Zoledronate) A New Weapon Against Tumor Cells

Rich66 · 07-18-2009, 12:58 PM

1: Cancer Lett. 2009 Jul 2. [Epub ahead of print] Links: Zoledronic acid induces apoptosis and changes the TRAIL/OPG ratio in breast cancer cells.

Rachner TD, Singh SK, Schoppet M, Benad P, Bornhäuser M, Ellenrieder V, Ebert R, Jakob F, Hofbauer LC.
Division of Gastroenterology and Endocrinology, Department of Medicine, Philipps-University, Marburg, Germany; Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technical University, Dresden, Germany.
Breast cancer has a propensity to metastasize to bone, thus causing pathological fractures. Bisphosphonates are established drugs in the treatment of bone metastasis that inhibit osteoclast activity and interrupt the vicious cycle of osteoclast-tumor cell interactions. We evaluated the direct effects of zoledronic acid on estrogen receptor (ER)-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells. While zoledronic acid (100muM) inhibited MDA-MB-231 cell proliferation after 72h, and induced apoptosis via activation of caspase-3 and -7, it had only minor effects on MCF-7 cells. In addition, zoledronic acid induced apoptosis by up-regulating TNF-related apoptosis-inducing ligand (TRAIL) in MDA-MB-231 cells (p<0.01), but had no effect on the expression of its decoy receptor osteoprotegerin (OPG). In MCF-7 cells, both cytokines were suppressed by zoledronic acid. In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer.
PMID: 19577359 [PubMed - as supplied by publisher]

Hmmmm. So..it showed little response in Er+ cells despite suppresssing more cytokines than when used on ER-????

07-18-2009, 12:58 PM	#19
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	1: Cancer Lett. 2009 Jul 2. [Epub ahead of print] Links Zoledronic acid induces apoptosis and changes the TRAIL/OPG ratio in breast cancer cells. Rachner TD, Singh SK, Schoppet M, Benad P, Bornhäuser M, Ellenrieder V, Ebert R, Jakob F, Hofbauer LC. Division of Gastroenterology and Endocrinology, Department of Medicine, Philipps-University, Marburg, Germany; Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technical University, Dresden, Germany. Breast cancer has a propensity to metastasize to bone, thus causing pathological fractures. Bisphosphonates are established drugs in the treatment of bone metastasis that inhibit osteoclast activity and interrupt the vicious cycle of osteoclast-tumor cell interactions. We evaluated the direct effects of zoledronic acid on estrogen receptor (ER)-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells. While zoledronic acid (100muM) inhibited MDA-MB-231 cell proliferation after 72h, and induced apoptosis via activation of caspase-3 and -7, it had only minor effects on MCF-7 cells. In addition, zoledronic acid induced apoptosis by up-regulating TNF-related apoptosis-inducing ligand (TRAIL) in MDA-MB-231 cells (p<0.01), but had no effect on the expression of its decoy receptor osteoprotegerin (OPG). In MCF-7 cells, both cytokines were suppressed by zoledronic acid. In conclusion, zoledronic acid enhanced the TRAIL-to-OPG ratio in TRAIL-sensitive MDA-MB-231 cells, indicating that the TRAIL/OPG cytokine system is a bisphosphonate-responsive target in breast cancer. PMID: 19577359 [PubMed - as supplied by publisher] Hmmmm. So..it showed little response in Er+ cells despite suppresssing more cytokines than when used on ER-????