Use of raw Euphorbia tirucalli extract for inhibition of ascitic Ehrlich tumor

Santos, Orlando José dos; Filho, Euler Nicolau Sauaia; Nascimento, Flávia R.F.; Júnior, Francisco Cardoso Silva; Fialho, Eder Magalhães Silva; Santos, Rayan Haquim Pinheiro; Santos, Rennan Abud Pinheiro; Serra, Izabel Cristina Portela Bogéa

doi:10.1590/0100-69912016001005

Cited by 8 publications

(9 citation statements)

References 21 publications

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“…It has also been shown that autophagic structures are present in gliomas in vivo after treatments [38]. Moreover, our results agree with other studies, which have used TMZ, arsenic trioxide and berberine (natural compound) to induce autophagic cell death in malignant glioma cells, and shown that Baf enhanced the effect of TMZ and arsenic trioxide, by inducing apoptosis [39,40]. In summary, these results suggest that autophagy plays a crucial role in the antiproliferative mechanism of euphol against glioma cells, and that inhibiting autophagy will improve the effectiveness of treatment.…”

Section: Discussionsupporting

confidence: 92%

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

et al. 2018

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Glioblastoma (GBM) is the most frequent and aggressive type of brain tumor. There are limited therapeutic options for GBM so that new and effective agents are urgently needed. Euphol is a tetracyclic triterpene alcohol, and it is the main constituent of the sap of the medicinal plant Euphorbia tirucalli. We previously identified anti-cancer activity in euphol based on the cytotoxicity screening of 73 human cancer cells. We now expand the toxicological screening of the inhibitory effect and bioactivity of euphol using two additional glioma primary cultures. Euphol exposure showed similar cytotoxicity against primary glioma cultures compared to commercial glioma cells. Euphol has concentration-dependent cytotoxic effects on cancer cell lines, with more than a five-fold difference in the IC values in some cell lines. Euphol treatment had a higher selective cytotoxicity index (0.64-3.36) than temozolomide (0.11-1.13) and reduced both proliferation and cell motility. However, no effect was found on cell cycle distribution, invasion and colony formation. Importantly, the expression of the autophagy-associated protein LC3-II and acidic vesicular organelle formation were markedly increased, with Bafilomycin A1 potentiating cytotoxicity. Finally, euphol also exhibited antitumoral and antiangiogenic activity in vivo, using the chicken chorioallantoic membrane assay, with synergistic temozolomide interactions in most cell lines. In conclusion, euphol exerted in vitro and in vivo cytotoxicity against glioma cells, through several cancer pathways, including the activation of autophagy-associated cell death. These findings provide experimental support for further development of euphol as a novel therapeutic agent for GBM, either alone or in combination chemotherapy.

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Section: Discussionsupporting

confidence: 92%

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

et al. 2018

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“…Meroterpenoids Ehrlich's tumor exhibits strong inflammatory phenomena, including edema and inflammatory infiltrates, which are believed to play an essential role in tumor growth in various types of cancer [42,43,44,45,46]. But the anti-inflammatory effects were reported by meroterpenoids [47] and were observed in this research showing that the extract reduces inflammation, reducing the tumor by an indirect route.…”

Section: P Purpurogenum Extract Showed Activity Against Ehrlich's Somentioning

confidence: 60%

Penicillium purpurogenumexerts antitumor effects and ameliorates inflammations in Erlich mice model

Teles

Pontes

Guimarães

et al. 2020

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ABSTRACTBackgroundThe bioactive metabolites production contributes to the resistance of fungi towards adverse environmental conditions. Some metabolites often have interesting health-promoting activities. This study addressed the anti-tumoural properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil.MethodsThe extract obtained from the polished environment strain P. purpurogenum was fermented, filtered, concentrated and lyophilized, giving rise to the Ethyl Acetate Extracellular Extract (EAE). The metabolites of the extracellular extract of P. purpurogenum were studied using direct infusion mass spectrometry. The solid Ehrlic tumor model was used to evaluate the extract antitumor activity. Female Swiss mice were divided in groups (n=10/group) as follow: Negative control (CTL-) treated with phosphate buffered solution; Positive Control (CTL+) treated with cyclophosphamide (25mg/mL); Extracts treatment at doses 4, 20 and 100mg/Kg; Animals without tumor or treatment (Sham); and animals without tumor treated with intermediate dose (EAE20). All treatments were performed intraperitoneally, daily during 15 days. After, the animals were eutanized and the tumor, lymphoid organs and serum were used for immunological, histological and biochemical parameters evaluation.ResultsThe extract was rich in meroterpenoids. All doses of the extract significantly reduced tumor size compared to CLT- and were associated with 100% survival. Histologically, the 20 and 100mg/kg doses reduced tumour-associated inflammation and tumour necrosis. The extract also reduced cellular infiltration of lymphoid organs and circulating TNF-α levels when compared with CLT-. The extract did not induce weight loss and renal or hepatic toxic changes.ConclusionsThese results indicate that P. purpurogenum from a polluted marine environment produce hybrid natural products of the terpenoid pathway that exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a biotechnological approach for the production of antitumour agents.

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“…These results indicated that euphol is an active ingredient of E. tirucalli that exerts anticancer effects, possibly by arresting cell cycle progression of cancer cells. Santos et al (13) also demonstrated that E. tirucalli extract inhibited the growth of Ehrlich ascites tumor. Furthermore, euphol inhibited the growth of human gastric cancer cells by modulating apoptosis mediated by ERK1/2 and cyclin D1 (7).…”

Section: Introductionmentioning

confidence: 94%

“…Recently, Palharini et al (12) investigated eutirucallin, a lectin with antitumor and antimicrobial properties. Some of these active components have been reported to have biological activities, such as preventive anticancer activity, antitumor, antimutagenic, antibacterial, laxative, antiseptic, disinfectant, anti-inflammatory, antistreptococcal, antiparasitic, antiulcer, analgesic, antiasthmatic and expectorant properties, as well as anticancer effects against specific types of cancer of the breast, lung, cervix, esophagus and mouth (13).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of Euphorbia tirucalli latex on murine B16/F10 melanoma cells and lung metastasis

et al. 2019

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Euphorbia tirucalli (E. tirucalli) is a tropical and subtropical plant that produces a latex which is used for several purposes. The components of E. tirucalli latex include triterpenes, diterpenes and steroids. The aim of the present study was to evaluate the effects of diluted E. tirucalli latex on murine B16/F10 melanoma cells and lung metastasis. For this purpose, an in vitro study was first performed, in which B16/F10 cells were treated with diluted (1/2 to 1/11,192) E. tirucalli latex. In a second study, B16/F10 melanoma cells were inoculated into the tail vein of mice to generate lung metastases; the mice then received 0.467 µg of latex diluted in 200 ml saline by gavage for 14 days. A significant decrease in B16/F10 cell viability was observed using the MTT assay at 24 and 48 h after treatment with E. tirucalli latex. In addition, a significant decrease in the volume fraction occupied by B16/F10 metastatic colonies in the lungs was observed in mice treated with E. tirucalli latex. These results confirm the antineoplastic effects of diluted E. tirucalli latex.

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Use of raw Euphorbia tirucalli extract for inhibition of ascitic Ehrlich tumor

Abstract: Treatment with ETHE after inoculation of Ehrlich Tumor decreases its development and increases survival and the bone marrow cellularity, thus reducing the myelosuppression present in the Ehrlich Tumor bearing mice.

Cited by 8 publications

References 21 publications

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

Euphol, a tetracyclic triterpene, from Euphorbia tirucalli induces autophagy and sensitizes temozolomide cytotoxicity on glioblastoma cells

Penicillium purpurogenumexerts antitumor effects and ameliorates inflammations in Erlich mice model

Inhibitory effects of Euphorbia tirucalli latex on murine B16/F10 melanoma cells and lung metastasis

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