Antitumor Agents LIX: Effects of Quassinoids on Protein Synthesis of a Number of Murine Tumors and Normal Cells

Hall, Iris H.; Liou, Y.F.; Lee, K.H.; Chaney, Stephen G.; Willingham, Walker

doi:10.1002/jps.2600720612

Cited by 21 publications

(12 citation statements)

References 11 publications

(1 reference statement)

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“…Glaucarubinone was previously found to be active against leukemia cells (Ghosh et al, 1977), human nasopharynx epidermoid carcinoma (KB) (Wright et al, 1993), and P-388 lymphocytic leukemia in mice (Kupchan et al, 1976;Grieco et al, 1993). The proposed mechanism of action of quassinoids, including glaucarubinone, is related to the inhibition of the protein synthesis (Hall et al, 1983). Other biological activities of glaucarubinone are reported, like antiprotozoal (Wright et al, 1993), insecticidal (Polonsky et al, 1989) and antilarval (Leskinen et al, 1984).…”

Section: Resultsmentioning

confidence: 93%

Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines

Mesquita

Paula

Pessoa

et al. 2009

Journal of Ethnopharmacology

139

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Section: Resultsmentioning

confidence: 93%

Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines

Mesquita

Paula

Pessoa

et al. 2009

Journal of Ethnopharmacology

139

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“…Inhibition of overall protein synthesis was observed in rabbit reticulocytes, as well as in cell lines derived from lymphocytic leukemia, Ehrlich carcinoma, hepatoma, and lymphoid leukemia (41)(42)(43)(44). It should be noted that nanomolar concentrations of brusatol were used in our study, whereas micromolar concentrations were used in the in vitro studies conducted by the aforementioned groups (42,43). In our study, brusatol (20-80 nM) specifically inhibited the protein level of Nrf2 in a dose-dependent manner (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…This group reported that bruceantin, brucein D, brucein E, bruceoside A, and brusatol inhibited DNA, RNA, and protein synthesis as well as oxidative phosphorylation in p-388 lymphocytic leukemia cells (39,40). Inhibition of overall protein synthesis was observed in rabbit reticulocytes, as well as in cell lines derived from lymphocytic leukemia, Ehrlich carcinoma, hepatoma, and lymphoid leukemia (41)(42)(43)(44). It should be noted that nanomolar concentrations of brusatol were used in our study, whereas micromolar concentrations were used in the in vitro studies conducted by the aforementioned groups (42,43).…”

Section: Discussionmentioning

confidence: 99%

Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism

Ren

Villeneuve

Jiang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

557

506

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The major obstacle in cancer treatment is the resistance of cancer cells to therapies. Nrf2 is a transcription factor that regulates a cellular defense response and is ubiquitously expressed at low basal levels in normal tissues due to Keap1-dependent ubiquitination and proteasomal degradation. Recently, Nrf2 has emerged as an important contributor to chemoresistance. High constitutive expression of Nrf2 was found in many types of cancers, creating an environment conducive for cancer cell survival. Here, we report the identification of brusatol as a unique inhibitor of the Nrf2 pathway that sensitizes a broad spectrum of cancer cells and A549 xenografts to cisplatin and other chemotherapeutic drugs. Mechanistically, brusatol selectively reduces the protein level of Nrf2 through enhanced ubiquitination and degradation of Nrf2. Consequently, expression of Nrf2-downstream genes is reduced and the Nrf2-dependent protective response is suppressed. In A549 xenografts, brusatol and cisplatin cotreatment induced apoptosis, reduced cell proliferation, and inhibited tumor growth more substantially when compared with cisplatin treatment alone. Additionally, A549-K xenografts, in which Nrf2 is expressed at very low levels due to ectopic expression of Keap1, do not respond to brusatol treatment, demonstrating that brusatol-mediated sensitization to cisplatin is Nrf2 dependent. Moreover, a decrease in drug detoxification and impairment in drug removal may be the primary mechanisms by which brusatol enhances the efficacy of chemotherapeutic drugs. Taken together, these results clearly demonstrate the effectiveness of using brusatol to combat chemoresistance and suggest that brusatol can be developed into an adjuvant chemotherapeutic drug.

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“…Simalikalactone D is active against Rous sarcoma oncogenic virus (Pierré et al, 1980), Herpes simplex type 1 virus, Vesicular stomatitis virus, Poliomyelitis and Semliki forest virus (Apers et al, 2002), while shinjulactone is active against HIV virus (Okano et al, 1996). Previous reports also found these compounds elicit anti-inflammatory activity (Guo et al, 2009;Hall et al, 1983). In addition,Beyond them brusatol, as well as samaderins X and B, can be highlighted (Kitagawa et al, 1996).…”

Section: Other Biological Activitiesmentioning

confidence: 86%

Simaroubaceae family: botany, chemical composition and biological activities

Alves

Miranda

Soares

et al. 2014

Revista Brasileira de Farmacognosia

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Antitumor Agents LIX: Effects of Quassinoids on Protein Synthesis of a Number of Murine Tumors and Normal Cells

Cited by 21 publications

References 11 publications

Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines

Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines

Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism

Simaroubaceae family: botany, chemical composition and biological activities

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