The Anticancer Agent Prodigiosin Is Not a Multidrug Resistance Protein Substrate

Elahian, Fatemeh; Moghimi, Bahareh; Dinmohammadi, Farideh; Ghamghami, Mahsa; Hamidi, Mehrdad; Mirzaei, Seyed Abbas

doi:10.1089/dna.2012.1902

Cited by 60 publications

(44 citation statements)

References 27 publications

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“…As demonstrated by proliferation assays, obatoclax retained its antiproliferative efficacy in cell lines highly overexpressing BCRP, MRP2 or P‐gp. This indicates that obatoclax is probably not transported by either of these drug transporters because active transport out of the cells is the fundamental principle for efflux transporter‐mediated drug resistance [30,47–51]. This confirms an earlier study on P‐gp transport, where obatoclax was effective irrespective of ABCB1 expression level [12].…”

Section: Discussionsupporting

confidence: 85%

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Obatoclax as a perpetrator in drug–drug interactions and its efficacy in multidrug resistance cell lines

Theile

Allendorf

Köhler

et al. 2015

Journal of Pharmacy and Pharmacology

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Section: Discussionsupporting

confidence: 85%

“…This is a clear advantage compared with other Bcl‐2 inhibitors like ABT‐737 or ABT‐263 being substrates of P‐gp being one cause for resistance towards these drugs [52]. Another advantage of obatoclax is its additional inhibition of Mcl‐1, making it superior to compounds like ABT‐737 [43–55]…”

Section: Discussionmentioning

confidence: 99%

Obatoclax as a perpetrator in drug–drug interactions and its efficacy in multidrug resistance cell lines

Theile

Allendorf

Köhler

et al. 2015

Journal of Pharmacy and Pharmacology

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“…These findings suggest that prodigiosin has a long-term effect on CRCSC self-renewal. Previous studies have shown that prodigiosin is retained in the mitochondria in cancer cells (47) and is not a substrate for multidrug resistance efflux pumps (48). These properties of prodigiosin could contribute to the sustained effects observed.…”

Section: Discussionmentioning

confidence: 96%

Small-Molecule Prodigiosin Restores p53 Tumor Suppressor Activity in Chemoresistant Colorectal Cancer Stem Cells via c-Jun-Mediated ΔNp73 Inhibition and p73 Activation

et al. 2016

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Tumor suppressor p53 is frequently mutated or inactivated in colorectal cancer. In contrast, p53 family member p73 is rarely mutated in colorectal cancer and p73 activation elicits p53-like tumor suppression. Colorectal cancer stem cells (CRCSC) comprise a rare self-renewing subpopulation that contributes to tumor maintenance and chemoresistance. p53 restoration is known to target CRCSCs, but p73 restoration in CRCSCs has not been examined. In this study, we investigated the effects of the small-molecule prodigiosin, which restores the p53 pathway in tumor cells via p73 activation, on CRCSCs in vitro and in vivo. Prodigiosin prevented colonosphere formation independent of p53 status and reduced the viability of self-renewing, 5-fluorouracil-resistant Aldefluor positive [Aldefluor(þ)] CRCSCs in vitro. Furthermore, prodigiosin inhibited the growth of xenograft tumors initiated with Aldefluorþ cells without toxic effects and limited the tumorigenic potential of these cells. Consistently, prodigiosin induced activation of a p53-responsive luciferase reporter in colonospheres, Aldefluor(þ) cells, and tumor xenografts. Mechanistic studies revealed that prodigiosin increased the levels of p73 and reduced levels of the oncogenic N-terminally truncated isoform DNp73 in Aldefluor(þ) cells. Accordingly, p73 knockdown or DNp73 overexpression suppressed prodigiosinmediated inhibition of colonosphere formation. Moreover, prodigiosin increased levels of the transcription factor c-Jun, a regulator of p73 and DNp73, in both the cytoplasm and nucleus. cJun knockdown attenuated prodigiosin-mediated p53-reporter activation, DNp73 downregulation, p73 activation, and cell death. Collectively, our findings highlight the previously uncharacterized use of p73-activating therapeutics to target CRCSCs.

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“…According to the Beer–Lambert equation, the slope of the line obtained by plotting the mean absorbance at any individual wavelengths versus serial dilutions (1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128, 1:256 mg/ml) of the test material represents the extinction coefficient (molar absorptivity). All experiments were performed three independent times …”

Section: Methodsmentioning

confidence: 99%

Diversity and ecotypic variation in the antioxidant and antigenotoxic effects of Thymus kotschyanus Boiss & Hohen

Afshari

Elahian

Ayari

et al. 2016

Flavour & Fragrance J

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Thymus species are amongst the most popular medicinal plants because of their biological effects and pharmacological properties, and they are widely used in folk medicine for many disorders. Fourteen ecotypic Thymus kotschyanus essential oils were isolated, and the biological functionalities of ecotypic oils were characterized in terms of free radical scavenging and antigenotoxic properties. The most abundant ecotypic oil constituents were thymol and carvacrol (27.2–75.6%). The oils produced scavenging capacity, bleaching inhibitory capacity, and COMET‐inhibitory capacity values in a dose‐dependent manner ranging from 0.15 to 4.79 mg/ml, 0.04 to 3.1 mg/ml and 0.03 to 5.00 mg/ml, respectively. The benefits of T. kotschyanus essential oils from different regions vary, and they represent an inexpensive source of natural substances that have the potential to be used as antioxidative and antigenotoxic agents. Although the impacts of the microenvironment, climate difference and agronomical condition on the medical benefits of the plant were complex and highly context dependent, some correlations among the biological effects, main essential constituents, and the geographical environment were predicted. Copyright © 2016 John Wiley & Sons, Ltd.

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The Anticancer Agent Prodigiosin Is Not a Multidrug Resistance Protein Substrate

Cited by 60 publications

References 27 publications

Obatoclax as a perpetrator in drug–drug interactions and its efficacy in multidrug resistance cell lines

Obatoclax as a perpetrator in drug–drug interactions and its efficacy in multidrug resistance cell lines

Small-Molecule Prodigiosin Restores p53 Tumor Suppressor Activity in Chemoresistant Colorectal Cancer Stem Cells via c-Jun-Mediated ΔNp73 Inhibition and p73 Activation

Diversity and ecotypic variation in the antioxidant and antigenotoxic effects of Thymus kotschyanus Boiss & Hohen

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