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CeReS-18, a novel cell surface sialoglycopeptide, induces cell cycle arrest and apoptosis in a calcium-sensitive
N A Betz1, H K Fattaey, B A Westhoff
1Center for Basic Cancer Research, Division of Biology, Kansas State University, Manhattan 66506, USA.
Abstract:
Very few growth inhibitors have been identified which can inhibit the proliferation of a broad spectrum of human breast cancer cell lines. CeReS-18, a novel cell surface sialoglycopeptide growth inhibitor, can reversibly inhibit the proliferation of both estrogen receptor positive (MCF-7) and negative (BT-20) human breast cancer cell lines. In addition, at concentrations above those required for the reversible inhibition of cell proliferation, CeReS-18 can also induce cell death in MCF-7 cells. Changes in nuclear and cytoplasmic morphology, characteristic of apoptosis, were detected in MCF-7 cells treated with a cytotoxic concentration of CeReS-18, and internucleosomal DNA cleavage was also observed. The sensitivity of MCF-7 and BT-20 cells to the biological properties of CeReS-18 could be influenced by altering the calcium concentration in the extracellular growth medium, such that when the calcium concentration in the environment was decreased, and increased sensitivity to CeReS-18-induced growth inhibition and cytotoxicity were observed. The addition of the calcium chelating agent EGTA to MCF-7 cells, cultured in a normal calcium environment, could mimic the increased sensitivity to the biological effects of CeReS-18 observed under reduced calcium conditions.
Insights
A novel growth inhibitor, CeReS-18, effectively halts proliferation in diverse human breast cancer cells. Its efficacy, including inducing apoptosis, is enhanced by lower calcium levels, offering new therapeutic avenues.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Limited availability of broad-spectrum growth inhibitors for human breast cancer.
- Need for novel therapeutic agents targeting both estrogen receptor-positive and negative cell lines.
Purpose of the Study:
- To investigate the anti-proliferative and cytotoxic effects of CeReS-18 on human breast cancer cell lines.
- To explore the role of extracellular calcium concentration in modulating CeReS-18's biological activity.
Main Methods:
- Treatment of MCF-7 (ER+) and BT-20 (ER-) breast cancer cell lines with CeReS-18.
- Assessment of cell proliferation inhibition and induction of apoptosis (morphological changes, DNA fragmentation).
- Manipulation of extracellular calcium concentrations and use of EGTA to study calcium's influence.
Main Results:
- CeReS-18 demonstrated reversible inhibition of proliferation in both MCF-7 and BT-20 cells.
- Higher CeReS-18 concentrations induced apoptosis in MCF-7 cells, evidenced by morphological changes and DNA cleavage.
- Reduced extracellular calcium significantly enhanced sensitivity to CeReS-18's growth inhibitory and cytotoxic effects.
Conclusions:
- CeReS-18 is a novel sialoglycopeptide with broad-spectrum anti-cancer activity against human breast cancer cells.
- Extracellular calcium concentration is a critical factor influencing CeReS-18's efficacy.
- Targeting calcium levels could potentiate CeReS-18-based cancer therapies.