Cytotoxicity studies of chromium(III) complexes on human dermal fibroblasts

Shrivastava, H. Yamini; Ravikumar, T.; Natesan, Shanmugasundaram; Babu, Mary; Nair, Balachandran Unni

doi:10.1016/j.freeradbiomed.2004.09.029

Cited by 70 publications

(67 citation statements)

References 42 publications

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“…The bulk of evidence indicates that Cr (VI) readily crosses the cell membrane through the sulfate anion channel transport system [Jennette, 1979;Sugiyama, 1992], because the tetrahedral anionic structure of Cr (VI) is structurally similar to phosphate or sulfate ions and allows it to mimic these ions [Sugden and Stearns, 2000]. By contrast, Cr (III), which is octahedral [Shrivastava et al, 2005], does not readily cross the cell membrane. Once Cr (VI) is inside the cell, the studies of Gruber and Jennette [1978] indicate that the enzymes bound to the endoplasmic reticulum reduce it to Cr (III).…”

Section: Reduction Of Cr (Vi) To Cr (Iii) Via Interaction With Cellulmentioning

confidence: 99%

An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)

McCarroll

Keshava

Chen

et al. 2009

Environ and Mol Mutagen

100

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In response to the 2005 revised U.S Environmental Protection Agency's (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with additional information to determine whether the initiating step in carcinogenesis is through a mutagenic mode of action (MOA). This information is necessary to decide if age-dependent adjustment factors (ADAFs) should be applied to the risk assessment. Chromium (VI) [Cr (VI)], a carcinogen in animals and humans via inhalation, was reassessed by the National Toxicology Program (NTP) in 2-year drinking water studies in rodents. From these data, NTP concluded that the results with Cr (VI) showed clear evidence of carcinogenicity in male and female mice and rats. Cr (VI) is also mutagenic, in numerous in vitro assays, in animals (mice and rats) and in humans. Accordingly, Cr (VI) was processed through the MOA framework; postulated key steps in tumor formation were interaction of DNA with Cr (VI) and reduction to Cr (III), mutagenesis, cell proliferation, and tumor formation. Within the timeframe and tumorigenic dose range for early events, genetic changes in mice (single/double-stranded DNA breaks) commence within 24 hr. Mechanistic evidence was also found for oxidative damage and DNA adduct formation contributing to the tumor response. The weight of evidence supports the plausibility that Cr (VI) may act through a mutagenic MOA. Therefore, the Cancer Guidelines recommend a linear extrapolation for the oral risk assessment. Cr (VI) also induces germ cell mutagenicity and causes DNA deletions in developing embryos; thus, it is recommended that the ADAFs be applied.

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Section: Reduction Of Cr (Vi) To Cr (Iii) Via Interaction With Cellulmentioning

confidence: 99%

An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)

McCarroll

Keshava

Chen

et al. 2009

Environ and Mol Mutagen

100

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“…From (8) and (10), the plots of k obs versus [Lac]are straight lines through the grid origin, and the plots of 1/k obs versus 1/[H + ] are linear with positive intercept. The rate constants of the rate determining step and activation parameters were obtained and presented in Table 2.…”

Section: Mechanismmentioning

confidence: 99%

“…The main sources of chromium pollution are mining, leather tanning, cement industries, electro plating, production of steel and other metal alloys, photographic material, and corrosive paints [5][6][7]. The hexavalent form of chromium has been demonstrated to be associated with the toxic parameters and classified as human carcinogen and mutagen [8]. Breathing high levels of hexavalent chromium can damage and irritate nose, lungs, stomach, and intestine [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Kinetic and Mechanistic Study of the Reduction of Chromium(VI) by Lactic Acid

Wang

Song

et al. 2008

International Journal of Inorganic Chemistry

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The kinetics and mechanism of the reduction of chromium(VI) by lactic acid (Lac) in aqueous acidic medium was studied with spectrophotometry in a temperature range of 298.15 K∼313. . There is no salt effect. Based on the experimental results, a probable reaction mechanism of oxidation was proposed. The rate equation derived from the mechanism could explain all the experimental phenomena. Activation parameters along with rate constant of the rate-determining step have been evaluated.

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“…Flow cytometry is regarded as one of the most powerful and specific methods for the integrated study of molecular and morphological events occurring during cell death and cell proliferation 37 . Generally, anticancer drugs inhibit the proliferation of cancer cell either by induction of cell cycle arrest or by apoptosis, or by the combination of both these modes.…”

Section: Impact Of Compound 4c On Cell Cycle Checkpoints and Apoptotimentioning

confidence: 99%

Novel thiosemicarbazides induced apoptosis in human MCF-7 breast cancer cells via JNK signaling

Malki

Elbayaa

Ashour

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this study, novel thiosemicarbazides and 1,3,4-oxadiazoles were synthesized and evaluated for their anticancer effects on human MCF-7 breast cancer cell lines. Among the synthesized derivatives studied, compound 2-(3-(4-chlorophenyl)-3-hydroxybutanoyl)-N-phenylhydrazinecarbothioamide 4c showed the highest cytotoxicity against MCF-7 breast cancer cells as it reduced cell viability to approximately 15% compared to approximately 25% in normal breast epithelial cells. Therefore, we focused on 4c for further investigations. Our data showed that 4c induced apoptosis in MCF-7 cells which was further confirmed by TUNEL assay. Western blotting analysis showed that compound 4c up-regulated the pro-survival proteins Bax, Bad and ERK1/2, while it down-regulated anti-apoptotic proteins Bcl-2, Akt and STAT-3. Additionally, 4c induced phosphorylation of SAPK/JNK in MCF-7 cells. Pretreatment of MCF-7 cells with 10 mM of JNK inhibitor significantly reduced 4c-induced apoptosis. Molecular docking results suggested that compound 4c showed a binding pattern close to the pattern observed in the structure of the lead fragment bound to JNK1. Collectively, the data of current study suggested that the thiosemicarbazide 4c might trigger apoptosis in human MCF-7 cells by targeting JNK signaling.

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Cytotoxicity studies of chromium(III) complexes on human dermal fibroblasts

Cited by 70 publications

References 42 publications

An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)

An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)

Kinetic and Mechanistic Study of the Reduction of Chromium(VI) by Lactic Acid

Novel thiosemicarbazides induced apoptosis in human MCF-7 breast cancer cells via JNK signaling

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