DNA Polymerase β Inhibitors from <i>Baeckea gunniana</i>

Deng, Junwen; Starck, Shelley R.; Hecht, Sidney M.

doi:10.1021/np990240w

Cited by 40 publications

(21 citation statements)

References 28 publications

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“…OA was previously shown to have an inhibitory effect on proliferation of human colon carcinoma cells through a reduction in the population of S phase cells along with a concomitant increase in the population of the G0/G1 cells indicating a possible role for OA in the G0/G1 checkpoint [5]. OA compounds were also previously shown to inhibit DNA polymerase beta and DNA topoisomeras [8,9], supporting our conclusion that Dex-OA could bring about its antiproliferation effect through inhibition of DNA replication.…”

Section: Discussionsupporting

confidence: 82%

Oleanolic acid derivative Dex-OA has potent anti-tumor and anti-metastatic activity on osteosarcoma cells in vitro and in vivo

Hua¹,

Zhang

et al. 2009

Invest New Drugs

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This study was undertaken to investigate the inhibitory effects of triterpenoid compound oleanolic acid and its synthetic derivatives on osteosarcoma cells in order to identify new therapeutic candidates for the treatment of this disease. We used the 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl tetrazolium bromide assay to assess the effect of oleanolic acid compounds on the proliferation of osteosarcoma cells. The effect of dextrose-oleanolic acid (the most potent oleanolic acid derivative) on apoptosis of osteosarcoma cells was evaluated using the Annexin-V method. The cell cycle of dextrose-oleanolic acid-treated cells was examined by flow cytometry, and the in vivo effects of dextrose-oleanolic acid were evaluated in a mouse osteosarcoma model. Oleanolic acid compounds had an overall inhibitory effect on the proliferation of osteosarcoma cells. Our in vitro data showed that the dextrose-oleanolic acid derivative brought about maximal inhibition of proliferation of osteosarcoma cells while inducing apoptosis. It could also inhibit the growth of osteosarcoma and decreased the rate of lung metastasis in vivo. Of the oleanolic acid derivatives, dextrose-oleanolic acid exhibited the most potent anti-osteosarcoma activity; it may represent a new frontier in the treatment of osteosarcoma.

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Section: Discussionsupporting

confidence: 82%

Oleanolic acid derivative Dex-OA has potent anti-tumor and anti-metastatic activity on osteosarcoma cells in vitro and in vivo

Hua¹,

Zhang

et al. 2009

Invest New Drugs

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“…DNA polymerase β plays a role in the repair of damaged DNA, as mentioned earlier. Oleanolic acid (83) inhibited all three of these enzymes, albeit weakly in the case of aromatase, and 90 was an effective DNA polymerase β inhibitor (Ganßer and Spiteller, 1995;Sun et al, 1999;Deng et al, 1999Deng et al, , 2000Hecht, 2003;Mizushina et al, 2003).…”

Section: Cancermentioning

confidence: 99%

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

et al. 2007

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Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook. f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-γ). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

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“…Compounds were isolated from Brackenridgea nitida [68], Bleasdalea bleasdalei [68], Freziera sp . [66], Baeckea gunniana [64], Tetracera boiviniana [63] and Sandoricum koetjape [70]. None yielded compounds with IC 50 values lower than 2 µM.…”

Section: Inhibiting Polβ-dependent Dna Synthesismentioning

confidence: 99%

Targeting DNA Polymerase ß for Therapeutic Intervention

Goellner

Svilar²,

Almeida³

et al. 2012

CMP

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DNA damage plays a causal role in numerous disease processes. Hence, it is suggested that DNA repair proteins, which maintain the integrity of the nuclear and mitochondrial genomes, play a critical role in reducing the onset of multiple diseases, including cancer, diabetes and neurodegeneration. As the primary DNA polymerase involved in base excision repair, DNA polymerase β (Polβ) has been implicated in multiple cellular processes, including genome maintenance and telomere processing and is suggested to play a role in oncogenic transformation, cell viability following stress and the cellular response to radiation, chemotherapy and environmental genotoxicants. Therefore, Polβ inhibitors may prove to be effective in cancer treatment. However, Polβ has a complex and highly regulated role in DNA metabolism. This complicates the development of effective Polβ-specific inhibitors useful for improving chemotherapy and radiation response without impacting normal cellular function. With multiple enzymatic activities, numerous binding partners and complex modes of regulation from post-translational modifications, there are many opportunities for Polβ inhibition that have yet to be resolved. To shed light on the varying possibilities and approaches of targeting Polβ for potential therapeutic intervention, we summarize the reported small molecule inhibitors of Polβ and discuss the genetic, biochemical and chemical studies that implicate additional options for Polβ inhibition. Further, we offer suggestions on possible inhibitor combinatorial approaches and the potential for tumor specificity for Polβ-inhibitors.

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DNA Polymerase β Inhibitors from Baeckea gunniana

Cited by 40 publications

References 28 publications

Oleanolic acid derivative Dex-OA has potent anti-tumor and anti-metastatic activity on osteosarcoma cells in vitro and in vivo

Oleanolic acid derivative Dex-OA has potent anti-tumor and anti-metastatic activity on osteosarcoma cells in vitro and in vivo

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

Targeting DNA Polymerase ß for Therapeutic Intervention

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