The anticancer agent PB-100, selectively active on malignant cells, inhibits multiplication of sixteen malignant cell lines, even multidrug resistant

Beljanski, Mirko

doi:10.1590/s1415-47572000000100005

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…[58] The blue-fluorescent zwitterionic agent was reported to rapidly accumulate in the nucleoli of U251 glioblastoma cells, but did not enter normal astrocyte control cells. [59] PB-100 appears to have a distinct binding preference for purine-rich nucleic acids.…”

Section: Molecules Interacting With the Nucleolus Or Modulating Nuclementioning

confidence: 99%

The Cell’s Nucleolus: an Emerging Target for Chemotherapeutic Intervention

Pickard

Bierbach

2013

ChemMedChem

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The transient nucleolus plays a central role in the upregulated synthesis of ribosomal RNA (rRNA) to sustain ribosome biogenesis, a hallmark of aberrant cell growth. This function, in conjunction with its unique pathohistological features in malignant cells and its ability to mediate apoptosis, renders this subnuclear structure a potential target for chemotherapeutic agents. In this Minireview, structurally and functionally diverse small molecules are discussed that have been reported to either interact with the nucleolus directly or perturb its function indirectly by acting on its dynamic components. These molecules include all major classes of nucleic acid-targeted agents, antimetabolites, kinase inhibitors, anti-inflammatory drugs, natural product antibiotics, oligopeptides, as well asnano-sized particles. Together, these molecules are invaluable probes of structure and function of the nucleolus. They also provide a unique opportunity to develop novel strategies for more selective and therefore better tolerated chemotherapeutic intervention. In this regard, inhibition of RNA polymerase I-mediated rRNA synthesis appears to be a promising mechanism of cancer cell kill. The recent development of molecules targeted at G-quadruplex forming rRNA gene sequences, which are currently undergoing clinical trials, seems to attest to the success of this approach.

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Section: Molecules Interacting With the Nucleolus Or Modulating Nuclementioning

confidence: 99%

The Cell’s Nucleolus: an Emerging Target for Chemotherapeutic Intervention

Pickard

Bierbach

2013

ChemMedChem

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“…Flavopereirine is a β -carboline alkaloid that can be extracted from the tree bark of several Geissospermum species [ 10 ] or chemically synthesized. Synthetic flavopereirine has been reported to selectively reduce human glioblastoma (U251) cell proliferation but only slightly inhibit normal astrocytes (CRL 1656) at a high concentration of 50 μg/mL [ 11 ]. Recent studies further demonstrated that flavopereirine significantly suppressed colorectal cancer cell growth in vitro and in vivo and induced apoptosis in breast cancer cells [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Chen

Yeh

et al. 2020

IJMS

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Autophagy is a potential target for the treatment of triple negative breast cancer (TNBC). Because of a lack of targeted therapies for TNBC, it is vital to find optimal agents that avoid chemoresistance and metastasis. Flavopereirine has anti-proliferation ability in cancer cells, but whether it regulates autophagy in breast cancer cells remains unclear. A Premo™ Tandem Autophagy Sensor Kit was used to image the stage at which flavopereirine affects autophagy by confocal microscopy. A plasmid that constitutively expresses p-AKT and siRNA targeting p38 mitogen-activated protein kinase (MAPK) was used to confirm the related signaling pathways by Western blot. We found that flavopereirine induced microtubule-associated protein 1 light chain 3 (LC3)-II accumulation in a dose- and time-dependent manner in MDA-MB-231 cells. Confocal florescent images showed that flavopereirine blocked autophagosome fusion with lysosomes. Western blotting showed that flavopereirine directly suppressed p-AKT levels and mammalian target of rapamycin (mTOR) translation. Recovery of AKT phosphorylation decreased the level of p-p38 MAPK and LC3-II, but not mTOR. Moreover, flavopereirine-induced LC3-II accumulation was partially reduced in MDA-MB-231 cells that were transfected with p38 MAPK siRNA. Overall, flavopereirine blocked autophagy via LC3-II accumulation in autophagosomes, which was mediated by the AKT/p38 MAPK signaling pathway.

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“…It is reported that Pao extract has anticancer effects against melanoma and glioblastoma cells in vitro. [4][5][6] Moreover, Pao extract suppresses cell growth and induces apoptosis of androgendependent prostate cancer LNCaP cells in vitro and in vivo. 7 These data suggest that Pao extract is a promising agent against cancer.…”

Section: Introductionmentioning

confidence: 99%

Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling

et al. 2013

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Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in South American medicine. A recent study showed that Pao extract repressed androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao extract asserts its anticancer effects on metastatic castration-resistant prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a dose-and time-dependent manner, through induction of apoptosis and cell cycle arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-x L , and XIAP expression, which were associated with the cleavage of PARP protein. Moreover, Pao extract treatment blocked PC3 cell migration and invasion. Mechanistically, Pao extract suppressed phosphorylation levels of AKT and NFκB/p65, NFκB DNA binding activity, and luciferase reporter activity. Pao inhibited TNFα-induced relocation of NFκB/p65 to the nucleus, NFκB/p65 transcription activity, and MMP9 activity as shown by zymography. Consistently, NFκB/p65 downstream targets involved in proliferation (Cyclin D1), survival (Bcl-2, Bcl-x L , and XIAP), and metastasis (VEGFa, MMP9, and GROα/CXCL1) were also downregulated by Pao extract. Finally, forced expression of NFκB/p65 reversed the growth inhibitory effect of Pao extract. Overall, Pao extract induced cell growth arrest, apoptosis, partially through inhibiting NFκB activation in prostate cancer cells. These data suggest that Pao extract may be beneficial for protection against CRPC.

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The anticancer agent PB-100, selectively active on malignant cells, inhibits multiplication of sixteen malignant cell lines, even multidrug resistant

Cited by 15 publications

References 19 publications

The Cell’s Nucleolus: an Emerging Target for Chemotherapeutic Intervention

The Cell’s Nucleolus: an Emerging Target for Chemotherapeutic Intervention

Flavopereirine Inhibits Autophagy via the AKT/p38 MAPK Signaling Pathway in MDA-MB-231 Cells

Pao Pereira Extract Suppresses Castration-Resistant Prostate Cancer Cell Growth, Survival, and Invasion Through Inhibition of NFκB Signaling

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