Cytotoxicity of etidronic acid to human breast cancer cells.

INTRODUCTION: Bisphosphonates have been used to treat Paget's disease, osteoporosis, and cancer metastases to the bone. The cancer chemotherapeutic potential of a first-generation bisphosphonate, etidronic acid, was evaluated by using MCF-7 human breast cancer cells. METHODS: In vitro cytotoxicity of etidronic acid to MCF-7 cells was estimated on the basis of clonogenicity assays, while cell cycle effects were determined by using flow cytometry. Mutagenicity of etidronic acid was detected by using denaturing high-pressure liquid chromatography analysis of cellular DNA amplified by PCR with primers for exons 5 through 8 of the human p53 gene. RESULTS: A 24-hour treatment with etidronic acid (10 mM) with or without strontium chloride was cytototoxic to MCF-7 cells. Etidronic acid caused a decrease in the S-phase population and an increase in the G2/M population. Mutations in the p53 gene were detected in MCF-7 cells treated with etidronic acid. Strontium chloride was not cytotoxic to cells. CONCLUSIONS: Cytotoxicity of etidronic acid to breast cancer cells may complement its inhibitory effects on bone resorption at the site of bone metastasis. Within the cell cycle, late S-phase cells are the most radioresistant, while cells at the G2/M border are the most sensitive. Therefore the decrease in S-phase population with corresponding increase in G2/M would make the cells more radiosensitive. This may be useful if etidronic acid were combined with radioactive strontium (89Sr, metastron) or external-beam radiotherapy for treating bone metastases. Tumor cells that survive etidronic acid treatment may acquire drug resistance because of mutations in the p53 tumor-suppressor gene.

Nicotine decreases the cytotoxicity of doxorubicin towards MCF-7 and KB-3.1 human cancer cells in culture.

The harmful effects of tobacco use and nicotine are well known. There is strong epidemiological evidence for smoking as a risk factor for cancer of the lung and oral cavity. The evidence for second-hand smoke as a risk factor for breast cancer is rapidly accumulating. The anthracycline doxorubicin is used in the treatment of many types of malignancies, including breast cancer. The effect of nicotine on doxorubicin toxicity was evaluated in MCF-7 and KB-3.1 cancer cell cultures. Nicotine partially inhibited doxorubicin toxicity towards MCF-7 and KB-3.1 cells, as judged by clonogenicity and flow cytometry assays. Flow cytometric analysis showed that < 10% of cells treated with doxorubicin underwent apoptosis, while necrosis was the major mode of cell death. Inhibition of apoptosis and necrosis in cancer cells by nicotine can diminish the effectiveness of doxorubicin in cancer therapy.

Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience.

More than two-thirds of the patients with osseous metastases experience debilitating bone pain, requiring some form of pain relief. Analgesics are limited in their efficacy. Palliative application of hemi-body external beam radiation therapy in the treatment of multiple osseous metastases also is limited due to toxicity associated with large treatment ports. Intravenous injections of bone seeking radioisotopes are effective in the palliation of pain with fewer side effects. Forty-one patients with multiple osseous metastases due to prostate and breast cancer were treated with strontium chloride 89 (89Sr) at the department of radiation oncology, in a university hospital. A retrospective analysis of these patients indicated that all subjects had severe pain that diminished their quality of life. Most of these patients had multiple co-morbid factors. Many were on opioids leading to adverse effects such as nausea, constipation, and drowsiness that required additional medication. Objective findings and evaluation of the responses were not always available for all patients. Following treatmentwith 89Sr, over two-thirds of the patients responded favorably and required lower doses of opioids.