New 13-pyridinealkyl berberine analogues intercalate to DNA and induce apoptosis in HepG2 and MCF-7 cells through ROS mediated p53 dependent pathway: biophysical, biochemical and molecular modeling studies

Chatterjee, Sabyasachi; Mallick, Sumana; Buzzetti, Franco; Fiorillo, Gaetano; Syeda, Tanjia Monir; Lombardi, Paolo; Saha, Krishna Das; Kumar, Gopinatha Suresh

doi:10.1039/c5ra17214d

Cited by 27 publications

(25 citation statements)

References 39 publications

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“…Cancer and normal cell lines were obtained from the National Centre for Cell Science, Pune. Standard protocol as described earlier was used for cell growth . Percentage growth inhibition (GI) values for all the cell lines at a concentration of 1 mg/mL of 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide were performed.…”

Section: Methodsmentioning

confidence: 99%

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Bhattacharjee

Ghosh

Sarkar

et al. 2017

J of Molecular Recognition

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The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single-stranded (ss) poly(A) > double-stranded calf thymus (CT) DNA > double-stranded poly(G)·poly(C) > clover leaf tRNA . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNA , very weak induced circular dichroism perturbation was seen. The interaction was predominantly exothermic, enthalpy driven, and entropy favored with CT DNA and poly(G)·poly(C), while it was entropy driven with poly(A) and tRNA . Intercalated state of harmaline inside poly(A), CT DNA, and poly(G)·poly(C) was shown by viscometry, ferrocyanide quenching, and molecular docking. All these findings unequivocally pointed out preference of harmaline towards ss poly(A) inducing self-structure formation. Furthermore, harmaline administration caused a significant decrease in proliferation of HeLa and HepG cells with GI of 28μM and 11.2μM, respectively. Nucleic acid fragmentation, cellular ultramorphological changes, decreased mitochondrial membrane potential, upregulation of p53 and caspase 3, generation of reactive oxygen species, and a significant increase in the G /M population made HepG more prone to apoptosis than are HeLa cells.

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Section: Methodsmentioning

confidence: 99%

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Bhattacharjee

Ghosh

Sarkar

et al. 2017

J of Molecular Recognition

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“…HepG 2 cells were grown at a density of 2 Â 10 5 cells/ml in 70 mm culture plate and treated with different concentrations of harmalol (7, 14, 21 mM) for 48 h. The other experimental protocol was followed as reported earlier [19].…”

Section: Cell Cycle Inhibition Analysismentioning

confidence: 99%

“…We tested the percentage of cell viability and calculated the GI 50 (50% growth inhibition) values for the above mentioned cell lines by MTT (1 mg/ml of the tetrazolium dye and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dissolved in phosphate buffer saline, pH 7.4) assay as reported earlier [19]. GI 50 was calculated by using the equation…”

Section: Cell Viability Test: Mtt Assaymentioning

confidence: 99%

DNA binding and apoptotic induction ability of harmalol in HepG2: Biophysical and biochemical approaches

Sarkar

Bhattacharjee

Bhadra

2016

Chemico-Biological Interactions

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“…The experimental protocol was followed an earlier report [20,26]. The histograms were obtained by BD Science FACS (Caliber), and the data were analyzed using the Cyflogic software.…”

Section: Cell Cycle Arrest Studymentioning

confidence: 99%

“…Cells were grown in DMEM (HiMedia) medium supplemented with 10% heat inactivated fetal bovine serum (HiMedia) and 1% antibiotic antimycotic solution (HiMedia), at 37°C with 5% CO 2 . The percentage of viable cells were calculated as the GI 50 ( 50% growth inhibition) values for the cell lines by MTT (1 mg/mL of the MTT) assay kit (Sigma), by the following formula as reported earlier [20,26].…”

Section: Mtt Assaymentioning

confidence: 99%

Therapeutic potential of harmaline, a novel alkaloid, against cervical cancer cells in vitro: Apoptotic induction and DNA interaction study

2018

J App Biol Biotech

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The study emphasizes the growth inhibitory effect of harmaline on HeLa (human cervical cancer) cell line and mode and mechanism of binding with CT DNA (calf thymus DNA). The results of cytotoxic study performed through MTT assay indicates that harmaline have concentration dependent growth inhibitory effect on HeLa cell line with GI 50 value of 28 µM. Furthermore, the alkaloid induced DNA damage and changes in mitochondrial membrane potential in the cell line. The alkaloid shows reactive oxygen species dependent cellular damage with significant arrest in G 2 /M population of the cell. Biophysical experiments further established the K i w value (product of cooperative binding affinity and the cooperative factor) of harmaline with CT DNA to be 5.60 × 10 5 M −1. Harmaline showed a progressive quenching of the fluorescence emission spectra. Circular dichroism study shows significant structural changes of DNAwith subsequent induction of optical activity in the bound achiral alkaloid molecule. The alkaloid stabilizes the DNA to 10°C. Intercalated state of harmaline inside DNA helix was shown by viscometric and ferrocyanide quenching. The results highlight the importance of alkaloid-DNA interaction for developing nucleic acid based therapeutic agents.

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New 13-pyridinealkyl berberine analogues intercalate to DNA and induce apoptosis in HepG2 and MCF-7 cells through ROS mediated p53 dependent pathway: biophysical, biochemical and molecular modeling studies

Abstract: A new series of 13-pyridinealkyl berberine analogues was synthesized and their DNA binding efficacy studied by employing spectroscopic, calorimetric and molecular modeling techniques.

Cited by 27 publications

References 39 publications

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

DNA binding and apoptotic induction ability of harmalol in HepG2: Biophysical and biochemical approaches

Therapeutic potential of harmaline, a novel alkaloid, against cervical cancer cells in vitro: Apoptotic induction and DNA interaction study

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