Dose- and time-dependent effects of doxorubicin on cytotoxicity, cell cycle and apoptotic cell death in human colon cancer cells

Lüpertz, Regine; Wätjen, Wim; Kahl, Regine; Chovolou, Yvonni

doi:10.1016/j.tox.2010.03.012

Cited by 169 publications

(131 citation statements)

References 36 publications

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“…Recently, the regulation of apoptosis has been proposed as a promising target for cancer chemotherapy [19,20]. Consistent with these reports, the data of our present study show clearly that kaempferol and doxorubicin/cisplatin combination induces strong apoptotic cell death that was ~ 3 fold higher than each agent alone.…”

Section: Combination Effect Of Kaempferol and Chemotherapeutic Drugssupporting

confidence: 92%

“…It is one of the most commonly consumed dietary supplements [8,18]. In recent studies, many reports demonstrated preventive and therapeutic efficacy of kaempferol in several epithelial cancer models [17,19]. Recent epidemiological studies show that many cancer patients use alternative medicine, mostly of herbal origin.…”

Section: Effect Of Kaempferol On Cell Growthmentioning

confidence: 99%

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Synergistic Growth Inhibitory Effect of Flavonol–kaempferol and Conventional Chemotherapeutic Drugs on Cancer Cells

Chepuri

Narasu

Devi

2017

Int J Pharm Pharm Sci

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Objective: The objective of the present study was to evaluate synergistic growth inhibitory effect of a flavonol, kaempferol in combination with chemotherapeutic drugs doxorubicin or cisplatin. Methods:The anti-proliferative activities of kaempferol, doxorubicin and cisplatin on human colorectal cancer cells (HCT-15) and human breast cancer (MDA MB 231) were analyzed by 3-(4,5-dimehylthiaol-2-yl)-2,5-diphenyltetraolium bromide (MTT) assay. Further, combinational studies were performed in both the cell lines to evaluate the interaction of drugs with kaempferol. The combination index (CI) method was used to assess the synergism of kaempferol with doxorubicin or cisplatin. Finally, morphological alterations associated with apoptosis were examined under fluorescent microscope.Results: All compounds showed dose-dependent growth inhibition in both HCT-15 and MDA MB 231 cells. The phytochemical kaempferol showed fifty percent inhibitory concentrations (IC50) at 120±3.2 µg/ml and 64±1.2 µg/ml on HCT-15 and MDA MB 231 respectively. IC50 concentrations of doxorubicin and cisplatin on both the cell lines were achieved at 49.6±0.5 µg/ml, 25.4±2.9 µg/ml and 44±1.8 µg/ml, 40.6±0.8 µg/ml respectively. Further, in vitro therapeutic effect (IC50) of doxorubicin and cisplatin in terms of cell growth inhibition on HCT-15 cells were achieved at their onefifth (10±0.83 µg/ml) and half (10±1.34 µg/ml) concentrations respectively when they were combined with 30 µg/ml of kaempferol individually. Simultaneously, on MDA-MB 231 cell line, the IC50 concentrations were reduced to 18±1.22 µg/ml and 15±1.87 µg/ml respectively i Conclusion:The study reveals the prominent synergism between the phytochemical, kaempferol and chemotherapeutic drugs doxorubicin or cisplatin which helps in elevating the therapeutic efficacy of drugs.n combination with 32 µg/ml of kaempferol. The combinational index studies revealed the synergistic association of kaempferol with doxorubicin and cisplatin individually in each cell line. The fluorescence imaging studies strongly supported the synergistic association between kaempferol and doxorubicin or cisplatin by confirming significant apoptotic cell death in both the cell lines which was ~3 fold higher than each agent alone.

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Section: Combination Effect Of Kaempferol and Chemotherapeutic Drugssupporting

confidence: 92%

Section: Effect Of Kaempferol On Cell Growthmentioning

confidence: 99%

Synergistic Growth Inhibitory Effect of Flavonol–kaempferol and Conventional Chemotherapeutic Drugs on Cancer Cells

Chepuri

Narasu

Devi

2017

Int J Pharm Pharm Sci

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“…20 One feature of DOX is to produce ROS via one-electron reduction to the corresponding semiquinone free radicals that then react rapidly with oxygen to generate superoxide radical anions. 1 The presence of oxidative stress on exposure of cells to SPIO NP may imply DNA damage and the early effect would be evidenced in cell cycle progression. 21 Mahmoudi et al determined the cytotoxicity of SPIO particles and their impact on the cell cycle studied with adhesive mouse fibroblast cell line (L929).…”

Section: Discussionmentioning

confidence: 99%

“…20 Lüpertz et al observed G2/M arrest and p53/p21 induction after treatment with 1 µM DOX and found G1 arrest accompanied by phosphorylation and activation of p53, but not enhanced expression of p21 after treatment with 5 µM DOX. 1 Javid et al observed that NF-κB and bax showed high expression, which caused significant apoptosis in A2780 and OVCAR-3 cell lines, while bcl-2 and surviving proteins had a sharp decrease in both the cell lines in group treated by DOX/POLYMER/SPIO. 11 Next, we investigated the effect of DOX and MagAlg-DOX on C-FOS and C-MYC, key genes involved in the regulation of many processes ongoing in the cell.…”

mentioning

confidence: 99%

In vitro cytotoxicity analysis of doxorubicin-loaded/superparamagnetic iron oxide colloidal nanoassemblies on MCF7 and NIH3T3 cell lines

Tománková¹,

Poláková²,

Pizova³

et al. 2015

IJN

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One of the promising strategies for improvement of cancer treatment is based on magnetic drug delivery systems, thus avoiding side effects of standard chemotherapies. Superparamagnetic iron oxide (SPIO) nanoparticles have ideal properties to become a targeted magnetic drug delivery contrast probes, named theranostics. We worked with SPIO condensed colloidal nanocrystal clusters (MagAlg) prepared through a new soft biomineralization route in the presence of alginate as the polymeric shell and loaded with doxorubicin (DOX). The aim of this work was to study the in vitro cytotoxicity of these new MagAlg–DOX systems on mouse fibroblast and breast carcinoma cell lines. For proper analysis and understanding of cell behavior after administration of MagAlg–DOX compared with free DOX, a complex set of in vitro tests, including production of reactive oxygen species, comet assay, cell cycle determination, gene expression, and cellular uptake, were utilized. It was found that the cytotoxic effect of MagAlg–DOX system is delayed compared to free DOX in both cell lines. This was attributed to the different mechanism of internalization of DOX and MagAlg–DOX into the cells, together with the fact that the drug is strongly bound on the drug nanocarriers. We discovered that nanoparticles can attenuate or even inhibit the effect of DOX, particularly in the tumor MCF7 cell line. This is a first comprehensive study on the cytotoxic effect of DOX-loaded SPIO compared with free DOX on healthy and cancer cell lines, as well as on the induced changes in gene expression.

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“…1,16,17 DMSO was used as the vehicle to deliver PNSE, and the final concentration of DMSO in all experiments was 0.1%. All experiments were done independently in triplicate per experimental point.…”

Section: Cell Culturementioning

confidence: 99%

Antioxidant, Antiproliferative, and Pro-Apoptotic Activities of a Saponin Extract Derived from the Roots of Panax notoginseng (Burk.) F.H. Chen

Zhao

Guo

et al. 2012

Journal of Medicinal Food

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Dietary and medicinal uses of Panax notoginseng have been associated with reduced risk of cancer. This study was designed to investigate the profiles of P. notoginseng saponin extract (PNSE), the major bioactive ingredients in P. notoginseng (Burk.) F.H. Chen, by high-performance liquid chromatography, and, for the first time, the anticancer effect of PNSE in the human colon cancer cell line LoVo was further evaluated. The major saponins present in PNSE were ginsenosides Rg1 (31.1%) and Rb1 (34.4%), and the total content of the eight saponins identified (notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, and Rd, and isomeric ginsenosides Rb2 and Rb3) was 81.7%, indicating that it was a highly purified standardized saponin extract. Furthermore, PNSE was found to have a markedly cytotoxic effect and antiproliferative activity against the LoVo cell line in a dose-and time-dependent manner. Flow cytometry analysis demonstrated that PNSE caused cell cycle arrest at S phase. Moreover, PNSE was found to possess antioxidative capacities in the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and hydroxyl radical scavenging assay in vitro. Taken together, the present results suggest that naturally occurring PNSE may provide significant natural defense against human colon cancer.KEY WORDS: antioxidant activity antitumor activity ginsenoside high-performance liquid chromatography notoginsenoside Panax notoginseng

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Dose- and time-dependent effects of doxorubicin on cytotoxicity, cell cycle and apoptotic cell death in human colon cancer cells

Cited by 169 publications

References 36 publications

Synergistic Growth Inhibitory Effect of Flavonol–kaempferol and Conventional Chemotherapeutic Drugs on Cancer Cells

Synergistic Growth Inhibitory Effect of Flavonol–kaempferol and Conventional Chemotherapeutic Drugs on Cancer Cells

In vitro cytotoxicity analysis of doxorubicin-loaded/superparamagnetic iron oxide colloidal nanoassemblies on MCF7 and NIH3T3 cell lines

Antioxidant, Antiproliferative, and Pro-Apoptotic Activities of a Saponin Extract Derived from the Roots of Panax notoginseng (Burk.) F.H. Chen

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