Tumor inhibitors. XLV. Crotepoxide, a novel cyclohexane diepoxide tumor inhibitor from Croton macrostachys

Kupchan, S. Morris; Hemingway, R.J.; Smith, R. M.

doi:10.1021/jo01264a033

Cited by 92 publications

(47 citation statements)

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“…This corroboration is demonstrated by Bridelia cathartica (Moshi et al, 2004;Suffness et al, 1988), Croton macrostachys (Moshi et al, 2004;Kupchan et al, 1969), Maytenus putterlickioides (Moshi et al, 2004;Shibuta, 1984), Ozoroa insignis (Moshi et al, 2004;Abreu et al, 1999), Psorospermum febrifugum (Moshi et al, 2006;Abou-Shoer et al, 1988;Kupchan et al, 1980), Phyllanthus engleri (Moshi et al, 2006;Ratnayake et al, 2009) and Ximenia americana (Moshi et al, 2004;Asres et al, 2001. This cutoff point has also been suggested elsewhere (Geran et al, 1972).…”

Section: Discussionsupporting

confidence: 65%

Brine shrimp toxicity of some plants used as traditional medicines in Kagera Region, north western Tanzania

Moshi

Innocent

Magadula

et al. 2010

Tanzania J Hlth Res

108

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__________________________________________________________________________________Abstract: Dichloromethane and/or ethanol extracts of 30 plants used as traditional medicines in Bukoba district, northwestern Tanzania were evaluated for brine shrimp toxicity. Among the 50 extracts tested, 32 extracts (64%) showed very low toxicity with LC50 values above 100 μg/ml. Among these 12 (24%) which had LC50 >500 μg /ml can be categorized as being practically non-toxic. Among the remaining extracts 19 (38%) which showed LC50 >100 < 500 μg /ml are also considered to be nontoxic. Extracts that showed LC50 results between 30-100 μg/ml have been categorized as mildly toxic; these include ethanol extracts of Lantana trifolia (LC50 32.3 μg/ml), Vernonia bradycalyx (LC50 33.9 μg/ml), Antiaris toxicaria (LC50 38.2 μg /ml) and Rubus rigidus (LC50 41.7 μg /ml) and the dichloromethane extracts of Gynura scandens (LC50 36.5 μg /ml) and Bridelia micrantha (LC50 32.0 μg /ml). The dichloromethane extracts of Picralima nitida (LC50 18.3 μg/ml) and Rubus rigidus (LC50 19.8 μg /ml), were only moderately toxic. Picralima nitida and Rubus rigidus extracts are only 1.1 and 1.2 less toxic than the standard drug, cyclophosphamide (LC50 16.3 μg /ml). In conclusion, the results indicate that among the 30 plants used as traditional medicines, 28 are safe for short term use. Picralima nitida and Rubus rigidus extracts are mildly toxic, but by comparison have a remote possibility to yield active anticancer compounds. _________________________________________________________________________________

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Section: Discussionsupporting

confidence: 65%

Brine shrimp toxicity of some plants used as traditional medicines in Kagera Region, north western Tanzania

Moshi

Innocent

Magadula

et al. 2010

Tanzania J Hlth Res

108

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“…1A), a highly substituted cyclohexane diepoxide linked with anticancer activity, was first isolated from the fruit of Croton macrostachys (1,2). More recently, crotepoxide was identified as a main component in Kaempferia rotunda (3), a member of the Zingiberaceae, or ginger family whose tuber has traditionally been used to treat pneumonia, bronchitis, abdominal pain, dysentery, diarrhea, cold, and obesity (4,5).…”

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confidence: 99%

Crotepoxide Chemosensitizes Tumor Cells through Inhibition of Expression of Proliferation, Invasion, and Angiogenic Proteins Linked to Proinflammatory Pathway

Prasad

Yadav

Sundaram

et al. 2010

Journal of Biological Chemistry

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Crotepoxide (a substituted cyclohexane diepoxide), isolated from Kaempferia pulchra (peacock ginger), although linked to antitumor and anti-inflammatory activities, the mechanism by which it exhibits these activities, is not yet understood. Because nuclear factor B (NF-B) plays a critical role in these signaling pathways, we investigated the effects of crotepoxide on NF-B-mediated cellular responses in human cancer cells. We found that crotepoxide potentiated tumor necrosis factor (TNF), and chemotherapeutic agents induced apoptosis and inhibited the expression of NF-B-regulated gene products involved in anti-apoptosis (Bcl-2, Bcl-xL, IAP1, 2 MCl-1, survivin, and TRAF1), apoptosis (Bax, Bid), inflammation (COX-2), proliferation (cyclin D1 and c-myc), invasion (ICAM-1 and MMP-9), and angiogenesis (VEGF). We also found that crotepoxide inhibited both inducible and constitutive NF-B activation. Crotepoxide inhibition of NF-B was not inducer-specific; it inhibited NF-B activation induced by TNF, phorbol 12-myristate 13-acetate, lipopolysaccharide, and cigarette smoke. Crotepoxide suppression of NF-B was not cell type-specific because NF-B activation was inhibited in myeloid, leukemia, and epithelial cells. Furthermore, we found that crotepoxide inhibited TAK1 activation, which led to suppression of IB␣ kinase, abrogation of IB␣ phosphorylation and degradation, nuclear translocation of p65, and suppression of NF-B-dependent reporter gene expression. Overall, our results indicate that crotepoxide sensitizes tumor cells to cytokines and chemotherapeutic agents through inhibition of NF-B and NF-B-regulated gene products, and this may provide the molecular basis for crotepoxide ability to suppress inflammation and carcinogenesis.Several chemotherapeutic, cytotoxic, and immunomodulating agents are commonly used to treat cancer. However, most modern medicines tend to target only one gene product or pathway at a given time. This is perhaps one of the major reasons that some of the recently discovered medicines are less effective. Besides being prohibitively expensive, many of these drugs are also associated with serious side effects and morbidity. Still, the search continues for an ideal treatment that has minimal side effects and is cost-effective. Therefore, traditional medicine, usually derived from plants is one of the alternatives to treat the chronic diseases including cancer. Although plantderived products have been used for centuries to treat various ailments, their active components and mechanisms are not fully understood. Identifying the active chemical entities and their molecular targets would facilitate the discovery of new clinical uses for such products.Crotepoxide (Fig. 1A), a highly substituted cyclohexane diepoxide linked with anticancer activity, was first isolated from the fruit of Croton macrostachys (1, 2). More recently, crotepoxide was identified as a main component in Kaempferia rotunda (3), a member of the Zingiberaceae, or ginger family whose tuber has traditionally been used to treat pneumonia, b...

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“…The 13 C NMR spectrum gave a total of eighteen carbon signals and together with the DEPT and HMQC spectra further confirmed that thirteen of these were protonated carbon signals while the other five were quaternary carbon signals. The compound was isolated and reported for the first time in 1968 from the fruits of the C. macrostachyus which was collected from Ethiopia [7] but the authors did not report the 13 C NMR. However, the authors reported only the chemical shifts of the protons and they reported five aromatic protons as a multiplet [7] but during our investigation the 1 H NMR spectra of the compound showed these five aromatic protons separately at different chemical shifts (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…The compound was isolated and reported for the first time in 1968 from the fruits of the C. macrostachyus which was collected from Ethiopia [7] but the authors did not report the 13 C NMR. However, the authors reported only the chemical shifts of the protons and they reported five aromatic protons as a multiplet [7] but during our investigation the 1 H NMR spectra of the compound showed these five aromatic protons separately at different chemical shifts (Table 1). Furthermore, the compound was also isolated and reported in 2004 from the fruits of the C. macrostachyus [3] but the authors reported the compound along with one novel compound without reporting the NMR data of crotepoxide.…”

Section: Resultsmentioning

confidence: 99%

Isolation of non-cytotoxic crotepoxide from the root bark of Croton macrostachyus and the reassignment of its structure

Desta¹,

Sewald²

2018

Bull. Chem. Soc. Eth.

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ABSTRACT.Crotepoxide was isolated for the first time from the root bark of Croton macrostachyus along with other known compounds. This compound along with other compounds was investigated for cytotoxicity and found to be not active against the human cervix carcinoma KB-3-1 cells in micromolar ranges. In addition, the 13 C NMR of crotepoxide is reassigned. The structures of the compounds in general were elucidated on the basis of extensive spectroscopic (1D and 2D) studies and literature data.

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Tumor inhibitors. XLV. Crotepoxide, a novel cyclohexane diepoxide tumor inhibitor from Croton macrostachys

Cited by 92 publications

References 1 publication

Brine shrimp toxicity of some plants used as traditional medicines in Kagera Region, north western Tanzania

Brine shrimp toxicity of some plants used as traditional medicines in Kagera Region, north western Tanzania

Crotepoxide Chemosensitizes Tumor Cells through Inhibition of Expression of Proliferation, Invasion, and Angiogenic Proteins Linked to Proinflammatory Pathway

Isolation of non-cytotoxic crotepoxide from the root bark of Croton macrostachyus and the reassignment of its structure

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