Antiproliferative Activity, Cell‐Cycle Dysregulation, and Cellular Differentiation: Salicyl‐ and Catechol‐Derived Acyclic 5‐Fluorouracil <i>O</i>,<i>N</i>‐Acetals against Breast Cancer Cells

Marchal, Juan A.; Rodríguez-Serrano, Fernando; Caba, Octavio; Aránega, Antonia; Gallo, Miguel Á.; Espinosa, Antonio; Campos, Joaquı́n M.

doi:10.1002/cmdc.200700142

Cited by 3 publications

(2 citation statements)

References 25 publications

(40 reference statements)

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“…3,15–18 The MCF-7 human breast cancer cell line has been used as an excellent experimental model 19,20 to improve the efficiency of different therapies before they are used on patients. The MCF-7 cell line is a useful cell line that can be used in many cancer researches and it is also an estrogen receptor-negative.…”

Section: Introductionmentioning

confidence: 99%

“…23,24 5-FU plays an important role in standard chemotherapy protocols for a range of solid tumors, including breast and colorectal cancers. 20,21 Considering the carcinogenic and mutagenic effects of Cd on healthy living cells, it seems beneficial to use a cancer cellular line, such as MCF-7. 3 It is particularly resistant to harmful solicitations of toxic metals, which provoke alterations to both cytoplasmic organelles and cytoskeleton proteins of different cellular lines.…”

Section: Introductionmentioning

confidence: 99%

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Cadmium influences the 5-Fluorouracil cytotoxic effects on breast cancer cells

Asara¹,

Marchal²,

Bandiera³

et al. 2012

Eur J Histochem

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The aim of the research was to evaluate a heavy metal, cadmium (Cd), which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-fluorouracil (5-FU), after exposure to different concentrations of cd. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 µM) to the cells treated with Cd (5 µM–20 µM) did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cadmium influences the 5-Fluorouracil cytotoxic effects on breast cancer cells

Asara¹,

Marchal²,

Bandiera³

et al. 2012

Eur J Histochem

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The selective cytotoxic activity in breast cancer cells by an anthranilic alcohol-derived acyclic 5-fluorouracil O,N-acetal is mediated by endoplasmic reticulum stress-induced apoptosis

Caba

Rodríguez-Serrano

Díaz‐Gavilán

et al. 2012

European Journal of Medicinal Chemistry

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Curcumin Reduces Cytotoxicity of 5-Fluorouracil Treatment in Human Breast Cancer Cells

Ferguson

Orlando²

2015

Journal of Medicinal Food

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Antimetabolites have proven successful as therapeutics for advanced-stage breast cancers, but are often accompanied by severe side effects that can limit treatment regimens. 5-Fluorouracil (5-FU), an antimetabolite that inhibits cell proliferation, has served an important role in standard chemotherapy protocols for a variety of solid tumors. Although reasonable response rates have been reported for 5-FU, continued exploration is necessary to improve clinical outcomes and reduce cytotoxic side effects that are an inherent problem for chemotherapeutic interventions. Because of its diverse anticancer properties, we explored whether by combining the natural product curcumin with 5-FU, synergistic improvements in preventing breast cancer cell proliferation and/or provide protection against 5-FU-induced cytotoxicity could be achieved. Indeed both curcumin and 5-FU inhibit DNA synthesis in MDA-MB-231 cells using BrdU incorporation assays; however, combined treatment showed no synergistic improvement. We next established the cytotoxicity profile for 5-FU in MDA-MB-231 cells using a tetrazolium-based cell viability assay and obtained an LD50 value of 28 μM. When 5-FU incubations were repeated with the addition of curcumin, the LD50 value increased to 200-300 μM, representing a 7-10-fold protection by curcumin against 5-FU cytotoxicity. These findings suggest that the addition of curcumin as an adjuvant therapy during 5-FU treatment might enhance the chemotherapeutic effectiveness of 5-FU by protecting normal cells from reduced viability and thus permitting higher dosing or longer treatment times. This would be especially important to those individuals who are plagued with severe cytotoxicities and require frequent interruptions, or even early termination of their treatment regimens.

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Antiproliferative Activity, Cell‐Cycle Dysregulation, and Cellular Differentiation: Salicyl‐ and Catechol‐Derived Acyclic 5‐Fluorouracil O,N‐Acetals against Breast Cancer Cells

Cited by 3 publications

References 25 publications

Cadmium influences the 5-Fluorouracil cytotoxic effects on breast cancer cells

Cadmium influences the 5-Fluorouracil cytotoxic effects on breast cancer cells

The selective cytotoxic activity in breast cancer cells by an anthranilic alcohol-derived acyclic 5-fluorouracil O,N-acetal is mediated by endoplasmic reticulum stress-induced apoptosis

Curcumin Reduces Cytotoxicity of 5-Fluorouracil Treatment in Human Breast Cancer Cells

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