Antitumor effect of BPR-DC-2, a novel synthetic cyclic cyanoguanidine derivative, involving the inhibition of MDR-1 expression and down-regulation of p-AKT and PARP-1 in lung cancer

Li, Shunlai; Huang, Chun Che; Lin, Chih‐Chan; Huang, Zih-Ning; Chern, Jyh-Haur; Lien, Hsiao-Yin; Wu, Yongyi; Cheng, Chia-Hui; Chang, Chia Yu; Chuu, Jiunn-Jye

doi:10.1007/s10637-009-9337-2

Cited by 10 publications

(2 citation statements)

References 38 publications

(39 reference statements)

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“…This phenomenon could further support the hypothesis that MDR reversal caused by P110-knockout may not be dependent on AKT expression levels. As some researchers have previously suggested, AKT activated by PI3K might be associated with the MDR of cancer cells [30,31]. Our studies proposed that the AKT-mediated MDR-enhancing pathway might be independent of the regulation of ABC transporter-mediated MDR and may be activated during crisis conditions, such as when the ABC transporters fail to efficiently pump toxins out of the cells.…”

Section: Crispr/cas9 Knockout Of the Pi3k 110α And 110β Subunits In Tmentioning

confidence: 49%

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Zhang

Wang

et al. 2020

Mol Cancer

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Background: PI3K/AKT is a vital signaling pathway in humans. Recently, several PI3K/AKT inhibitors were reported to have the ability to reverse cancer multidrug resistance (MDR); however, specific targets in the PI3K/AKT pathways and the mechanisms associated with MDR have not been found because many of the inhibitors have multiple targets within a large candidate protein pool. AKT activation is one presumed mechanism by which MDR develops during cancer treatment. Methods: The effects of inhibiting PI3K 110α and 110β by BAY-1082439 treatment and CRISPR/Cas9 knockout were examined to determine the possible functions of BAY-1082439 and the roles of PI3K 110α and 110β in the reversal of MDR that is mediated by the downregulation of P-gp and BCRP. Inhibition of AKT with GSK-2110183 showed that the downregulation of P-gp and BCRP is independent of generalized AKT inactivation. Immunofluorescence, immunoprecipitation, MTT, flow cytometry and JC-1 staining analyses were conducted to study the reversal of MDR that is mediated by P-gp and BCRP in cancer cells. An ATPase assay and a structural analysis were also used to analyze the potential mechanisms by which BAY-1082439 specifically targets PI3K 110α and 110β and nonspecifically influences P-gp and BCRP. Results: By inhibiting the activation of the PI3K 110α and 110β catalytic subunits through both the administration of BAY-1082439 and the CRISPR/Cas9 deletion of Pik3ca and Pik3cb, the ATP-binding cassette transporters P-gp/ ABCB1 and BCRP/ABCG2 were downregulated, thereby reestablishing the drug sensitivity of human epidermoid carcinoma and non-small cell lung cancer (NSCLC) MDR cells. Inhibition of AKT did not reverse the MDR mediated by P-gp or BCRP. The ABC family proteins and AKT may play MDR-enhancing roles independently. Conclusions: The reversal of the dual functions of ABC-transporter-mediated and AKT-activation-enhanced MDR through the inhibition or knockout of PI3K 110α or 110β promises to improve current strategies based on combined drug treatments to overcome MDR challenges.

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Section: Crispr/cas9 Knockout Of the Pi3k 110α And 110β Subunits In Tmentioning

confidence: 49%

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Zhang

Wang

et al. 2020

Mol Cancer

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“…Many natural occurring metabolites found in varieties of organisms contain guanidine moiety [3]. They have immense applications, especially in the field of medicines as neurotransmitter [6], cardiovascular, antihypertensive drugs [7], antibiotics [8,9], cytotoxic agents [10] and as an inhibitor of urokinase, responsible for a large number of malignancies including breast, lung, bladder, stomach, cervix, kidney and brain cancers [11][12][13]. On the other hand, ferrocene is one of the most favored building blocks in the construction of sensing platforms based on redox-active units due to the availability, stability and tailor ability of most of its derivatives [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Some New Ferrocenyl Phenyl Guanidines as Antibacterial, Antifungal Agents

Gul¹,

Nawaz²,

Badshah³

et al. 2016

JDDMC

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A series of new ferrocenylphenylguanidines (d-1 to d-4) were synthesized via multistep protocol. The purity of synthesized compounds were determined by melting point and TLC and their structures were established by various analytical techniques such as elemental analysis, multinuclear (1 H and 13 C) NMR and FTIR spectroscopy. The newly synthesized compounds were screened for antimicrobial activity against a panel of microorganisms (five bacterial strains, i.e three Gram positive, Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 6538), Bacillus subtilis (ATCC 6633) and two Gram negative, Klebsiella pneumonia (ATCC 43816), Escherichia coli (ATCC 15224) and three fungal strains, i.e. Fusa riumm oniliforme, Aspergillus fumigates and Aspergillusflavus. These compounds were found to have moderate antibacterial and good antifungal activities, especially for compounds having electronegative substituent on phenyl group.

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DNA/BSA Binding and Antimicrobial Properties of Biguanide‐Cu(II) Complexes

Ballı,

Gungor,

Kocer

et al. 2024

Chemistry & Biodiversity

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The biguanide Cu(II) complexes [Cu(L1‐4)2](ClO4)2 were synthesized and spectroscopic/analytical techniques were used to clarify their structures. Single crystals of complex [Cu(L4)2](ClO4)2 was obtained and its definite structure was determined by single crystal X‐ray diffraction study. The complexes [Cu(L1‐4)2](ClO4)2 were screened for their FSds‐DNA interactions by using UV‐Vis absorption and fluorescence spectroscopies. The complexes [Cu(L2)2](ClO4)2 and [Cu(L3)2](ClO4)2 were shown to exhibit higher affinity for binding DNA. Examining the EB‐DNA interaction, it is believed that the complexes interact with DNA through a groove binding mechanism. The interaction of complexes with BSA were observed through the quenching of the fluorescence emission. Complexes [Cu(L2)2](ClO4)2 and [Cu(L3)2](ClO4)2 show moderate binding affinity to BSA through a static mode. Additionally, the Cu(II) complexes were screened for their antibacterial activities against various bacterial strains. Complexes showed potential antimicrobial activity against Salmonella typhimurium, Bacillus cereus, Salmonella typhimurium and S. aureus.

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Antitumor effect of BPR-DC-2, a novel synthetic cyclic cyanoguanidine derivative, involving the inhibition of MDR-1 expression and down-regulation of p-AKT and PARP-1 in lung cancer

Cited by 10 publications

References 38 publications

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

The PI3K subunits, P110α and P110β are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

Synthesis and Biological Evaluation of Some New Ferrocenyl Phenyl Guanidines as Antibacterial, Antifungal Agents

DNA/BSA Binding and Antimicrobial Properties of Biguanide‐Cu(II) Complexes

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