Sesquiterpene Antitumor Agents: Inhibitors of Cellular Metabolism

Lee, Kuo Hsiung̀; Hall, Iris H.; Mar, Eng-Chun; Starnes, C.O.; Elgebaly, Salwa A.; Waddell, Thomas G.; Hadgraft, R. I.; Ruffner, C. G.; Weidner, Ivonne

doi:10.1126/science.191909

Cited by 208 publications

(92 citation statements)

References 19 publications

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“…However, our work and several other groups attribute an in vitro as well as in vivo antitumor activity also to helenalin [17,[40][41][42]. Both compounds have been shown to interfere with the signal transduction of NF-κB [35,43] playing a pivotal role both in inflammation and cancer [44,45].…”

Section: Discussionmentioning

confidence: 99%

Helenalin bypasses Bcl-2-mediated cell death resistance by inhibiting NF-κB and promoting reactive oxygen species generation

Hoffmann

Schwarzenberg

López-Antón

et al. 2011

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractEvasion of cell death by overexpression of anti-apoptotic proteins, such as Bcl-2, is commonly observed in cancer cells leading to a lack of response to chemotherapy.Hence, there is a need to find new chemotherapeutic agents that are able to overcome chemoresistance mediated by Bcl-2 and to understand their mechanisms of action. Helenalin, a sesquiterpene lactone ( and free intracellular iron as mediators of helenalin-induced cell death whereas activation of JNK and abrogation of Akt activity did not contribute to helenalin-elicited cell death. Our results highlight the NF-κB inhibitor helenalin as a promising chemotherapeutic agent to overcome Bcl-2-induced cell death resistance.

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Section: Discussionmentioning

confidence: 99%

Helenalin bypasses Bcl-2-mediated cell death resistance by inhibiting NF-κB and promoting reactive oxygen species generation

Hoffmann

Schwarzenberg

López-Antón

et al. 2011

Biochemical Pharmacology

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“…The inhibitory action of lactones may also be attributable to the presence of the O=C-C-CH 2 group which, according to Picman (1986), is responsible for the cytotoxicity. The inhibition of metabolic and enzymatic activities by SL may involve Michael-type reactions (Lee et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Genotoxic action of the sesquiterpene lactone glaucolide B on mammalian cells in vitro and in vivo

Burim¹,

Canalle²,

Lopes³

et al. 1999

Genet. Mol. Biol.

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Glaucolide B is a sesquiterpene lactone isolated from Vernonia eremophila Mart. (Vernonieae, Asteraceae) and has schistosomicidal, antimicrobial and analgesic activities. This study examined the cytotoxic and clastogenic activities of glaucolide B in human cultured lymphocytes and in bone marrow cells from BALB/c mice. The mitotic index (MI) and chromosomal aberrations were analyzed in both of the above systems, whereas sister chromatid exchanges (SCE) and the proliferation index (PI) were determined only in vitro. In human cultured lymphocytes, glaucolide B concentrations greater than 15 µg/ml of culture medium completely inhibited cell growth. At 4 µg/ml and 8 µg/ml of culture medium, glaucolide B significantly increased the frequency of chromosomal aberrations in lymphocytes and was also cytotoxic at concentrations ≥8 µg/ml; there was no increase in the frequency of SCE. Glaucolide B (160-640 mg/kg) did not significantly increase the frequency of chromosomal aberrations in mouse bone marrow cells nor did it affect cell division. Since glaucolide B showed no clastogenic action on mammalian cells in vivo but was cytotoxic and clastogenic in vitro, caution is needed in its medicinal use.

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“…The deviation of the methylene C is a maximum (0.45 A) in jeunicin. In view of the suggestion (see, for instance, Lee et al, 1977) that a lactone carrying an exocyclic methylene group is essential for biological activity, it would be of interest to investigate the correlation, if such exists, between the stereochemical features of the lactone as given in Table 3 and the biological activity of the molecules. It is relevant to mention that jeunicin is the most active in PS and KB tests among the cembranolides referred to here.…”

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confidence: 99%

Structure of peunicin

Chang¹,

Ciereszko²,

Hossain³

et al. 1980

Acta Crystallogr Sect B

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Abstract. C20H2604, M r = 330.4, orthorhombic, P212121, a = 9.5920(6), b = 11.6344 (10), c = 15.6859 (15) A, V = 1750.5 ,/t 3 at 113 + 2 K, Z = 4, D c = 1.213, D m = 1.223 Mg m -3 at 298 K. The compound is a toxic cembranolide extracted from the gorgonian Eunicea succinea. The molecular structure and absolute configuration are determined from X-ray data (2059 reflections measured at 113 K using Cu Ka radiation). The final R factor is 0.038.

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Sesquiterpene Antitumor Agents: Inhibitors of Cellular Metabolism

Cited by 208 publications

References 19 publications

Helenalin bypasses Bcl-2-mediated cell death resistance by inhibiting NF-κB and promoting reactive oxygen species generation

Helenalin bypasses Bcl-2-mediated cell death resistance by inhibiting NF-κB and promoting reactive oxygen species generation

Genotoxic action of the sesquiterpene lactone glaucolide B on mammalian cells in vitro and in vivo

Structure of peunicin

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