Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice

Nikhil, Kumar; Sharan, Shruti; Chakraborty, Ajanta; Bodipati, Naganjaneyulu; Peddinti, Rama Krishna; Roy, Partha

doi:10.1016/j.yexcr.2013.10.015

Cited by 35 publications

(28 citation statements)

References 63 publications

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“…Z-LEHD-FMK, a specific inhibitor of caspase-9, inhibited PTER-ITC-induced apoptosis by 50–55% (p<0.05), while Z-IETD-FMK, a specific inhibitor of caspase-8, inhibited PTER-ITC-induced apoptosis by 65-70% (p<0.05). In contrast, Z-LEHD-FMK inhibited PTER-ITC-induced apoptosis by 66–70% in MCF-7 cells, while Z-IETD-FMK did not effectively block PTER-ITC-induced apoptosis in this cell line, which confirmed previous reports [41]. Our data thus demonstrate that PTER-ITC-induced apoptosis is a caspase-dependent process that involves both caspase-8 and -9 in MDA-MB-231 cells and only caspase-9 in MCF-7 cells.…”

Section: Resultssupporting

confidence: 90%

“…Antibodies to caspase-9, Bax, Bcl-2, survivin, PTEN, PPARγ, β-actin, and small interfering RNA (siRNA) against PPARγ (sc-29455) and control (sc-37007; negative control for targeted siRNA transfection experiments; each consists of a scrambled sequence that will not specifically degrade any known cell mRNA) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA). PTER and PTER-ITC conjugate were synthesized in the asymmetric synthesis laboratory (Department of Chemistry, Indian Institute of Technology Roorkee, India) as reported [41].…”

Section: Methodsmentioning

confidence: 99%

“…The anti-proliferative effect of PTER and PTER-ITC was determined by the MTT assay as described [41]. Briefly, MCF-7 and MDA-MB-231 cells were seeded at a density of ∼5×103 cells/well in a 96-well microtiter plate and incubated overnight.…”

Section: Methodsmentioning

confidence: 99%

“…Recent research from our laboratory showed that PTER-ITC conjugate (Fig. 1A), a novel class of hybrid compound synthesized by appending an isothiocyanate moiety to the PTER backbone, can induce greater cytotoxicity in tumor cells than PTER alone [41], [42]. In human breast and prostate carcinoma cells, PTER-ITC induces strong anticancer activity at a much lower dose than the PTER parent compound [41], [42].…”

Section: Introductionmentioning

confidence: 99%

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Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

et al. 2014

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Trans-3,5-dimethoxy-4′-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARγ involvement in PTER-ITC action. Our results showed that when pre-treated with PPARγ antagonists or PPARγ siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARγ mRNA and protein levels in a dose-dependent manner and modulated expression of PPARγ-related genes in both breast cancer cell lines. This increase in PPARγ activity was prevented by a PPARγ-specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARγ activator. PTER-ITC-mediated upregulation of PPARγ was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARγ ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARγ activation pathway.

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Section: Resultssupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

et al. 2014

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“…In vitro cytotoxicity of MEZA was determined using previously used standard MTT assay (Nikhil et al, 2014). The experiment was performed in triplicate.…”

Section: In Vitro Cytotoxicity Assaymentioning

confidence: 99%

Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage byZanthoxylum alatum

Karmakar

Haldar

Chakraborty

et al. 2015

Pharmaceutical Biology

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Context: Many of the major chemotherapeutic agents are secondary metabolites found in nature. Zanthoxylum alatum Roxb. (Rutaceae) is traditionally used in the treatment of various diseases. Objective: The present study evaluates the apoptotic activity of methanol extract of Z. alatum (MEZA) on Ehrlich ascites tumor (EAT) in Swiss albino mice. Materials and methods: The presence of flavonoids in MEZA was standardized by HPLC. The in vitro cytotoxicity of MEZA was measured by the MTT assay. The in vivo antitumor activity of MEZA (100 and 200 mg/kg b.w., i.p. for 9 days) was also evaluated. On the 10th day, EAT tumor volume, cell viability, and hematological parameters were assayed. Apoptotic morphology was determined by acredine orange/ethedium bromide using fluorescence microscopy. Apoptosis percentage was measured by flow cytometric analysis using annexine-V-FITC. Also, DNA damage and bcl-2/bax were estimated by UV-method and western blot, respectively. Results and discussion: HPLC analysis revealed presence of three flavonoids, rutin, myricetin, and quercetin. MEZA showed satisfactory cytotoxicity in MTT assay (IC 50 ¼ 111.50 mg/ml). The extract significantly (p50.01) changed the tumor volume, viable, non-viable cell count, and hematological parameters towards the normal. Apoptotic activity of MEZA was confirmed by acridine orange/ethidium bromide staining, annexin-V-FITC staining, DNA fragmentation, and Bcl-2/Bax ratio. Conclusion: The study showed that MEZA has antitumor activity which may be due to the presence of flavonoids in the extract.

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Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

et al. 2016

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The serine/threonine kinase AKT/PKB plays a fundamental role in a wide variety of neuronal functions, including neuronal cell development, axonal growth, and synaptic plasticity. Multiple evidence link AKT signaling pathways to regulation of late phase long-term synaptic plasticity, synaptogenesis, and spinogenesis, as well as long-term memory formation. Nevertheless, the downstream effectors mediating the effects of AKT on early phase long-term potentiation (eLTP) are currently unknown. Here we report that using different regimes of pharmacological activation and inhibition of AKT activity in acute hippocampal slices, we found that AKT regulates the post-synaptic expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptors affecting solely the expression of eLTP, with no effect on its induction and maintenance. We further show that both maintenance of basal synaptic activity and expression of eLTP require plasma membrane tethering by activated AKT and that basal synaptic activity may be regulated via the direct effects of AKT1 on the expression level of post-synaptic AMPA receptors bypassing the canonical AKT signaling. Finally, we establish that eLTP expression requires the involvement of both the canonical AKT signaling pathways and the direct effect of AKT1 on AMPA receptor activity/expression in the post-synaptic membrane. © 2016 Wiley Periodicals, Inc.

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Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice

Cited by 35 publications

References 63 publications

Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

Anticancer Activities of Pterostilbene-Isothiocyanate Conjugate in Breast Cancer Cells: Involvement of PPARγ

Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage byZanthoxylum alatum

Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

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