Xylodiol from Xylopia langsdorfiana induces apoptosis in HL60 cells

Castello-Branco, Marianna Vieira S.; Tavares, Josean Fechine; Silva, Marcelo S.; Barbosa-Filho, José Maria; Anazetti, Maristella Conte; Frungillo, Lucas; Haun, Marcela; Diniz, Margareth F. F. Melo; Melo, Patrícia S.

doi:10.1590/s0102-695x2011005000135

Cited by 14 publications

(8 citation statements)

References 24 publications

(24 reference statements)

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“…In the present study, we showed that L-securinine inhibits HL-60 cell growth, induces apoptosis and enhances the expression of genes involved in the PI3K/AKT/mTOR signaling pathway in a dose-dependent manner. (28). Thus, our data demonstrated that L-securinine exhibits in vitro cytotoxic activity in HL-60 cells.…”

Section: Discussionsupporting

confidence: 63%

L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway

Han

Zhang

et al. 2014

Oncology Reports

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Abstract.The Securinega alkaloids are a class of natural products isolated from plants of the Euphorbiaceae family. L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 indicating its potential as an efficient natural antitumor drug with low toxicity. The aim of the present study was to investigate the apoptotic effects of L-securinine on HL-60 cells and to explore its potential underlying molecular mechanism(s) as an antitumor agent. HL-60 cells were cultured with L-securinine. The proliferation and changes in cell morphology were evaluated by Cell Counting Kit-8 (CCK-8) assay and electron microscopy, respectively. Induction of apoptosis and cell cycle progression were investigated by flow cytometry. The PI3K/AKT/mTOR pathway gene expression was measured by quantitative PCR (qPCR). L-securinine decreased the viability of HL-60 cells in a dose-and time-dependent manner, with IC 50 values at 24, 48 and 72 h post-treatment of 47.88, 23.85 and 18.87 µmol/l, respectively. Numerous apoptotic bodies were observed in the HL-60 cells treated with 25 µmol/l L-securinine for 48 h. L-securinine at 12.5, 25 and 50 µmol/l increased the rate of apoptosis in HL-60 cells, and G1/S phase progression was retarded. Furthermore, L-securinine induced downregulation of PI3K, AKT and mTOR gene expression and upregulation of PTEN gene expression in a dose-dependent manner. In conclusion, L-securinine induces apoptosis and inhibition of cell cycle progression in HL-60 cells by modulation of the PI3K/ AKT/mTOR pathway gene expression. These observations indicate the potential of L-securinine as an antitumor agent.

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Section: Discussionsupporting

confidence: 63%

L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway

Han

Zhang

et al. 2014

Oncology Reports

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“…Natural products still serve as the major source of new therapeutic agents [2,3]. More than two thirds of the drugs used in cancer treatment come directly from natural products or are developed using knowledge gained from the activity of their ingredients [4].…”

Section: Introductionmentioning

confidence: 99%

Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla

Xavier

Pita

Brito

et al. 2015

Zeitschrift Für Naturforschung C

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The chemical composition, antitumor activity and toxicity of the essential oil from Lippia microphylla leaves (OEL) were investigated. The major constituents were thymol (46.5%), carvacrol (31.7%), p-cymene (9%), and γ-terpinene (2.9%). To evaluate the toxicity of OEL in non-tumor cells, the hemolytic assay with Swiss mice erythrocytes was performed. The concentration producing 50% hemolysis (HC50) was 300 μg/mL. Sarcoma 180 tumor growth was inhibited in vivo 38% at 50 mg/kg, and 60% at 100 mg/kg, whereas 5-FU at 50 mg/kg caused 86% inhibition. OEL displays moderate gastrointestinal and hematological toxicity along with causing some alteration in liver function and morphology. However, the changes were considered reversible and negligible in comparison to the effects of several anticancer drugs. In summary, OEL displays in vivo antitumor activity and a moderate toxicity, which suggests further pharmacological study.

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“…Extracts of the bark, wood, and stem of X. aromatica [2,27] as well as numerous acetogenins isolated from this species [28,29] showed cytotoxicity to several tumor cell lines. In X. langsdorffiana, the isolated compound xylodiol was able to inhibit cell proliferation probably by involvement of the induction of cell differentiation and apoptosis induction [3,30]. Pita et al [31] showed that trachylobane-360, a diterpene isolated from X. langsdorffiana, displays antitumor effects in vitro and in vivo, without substantial systemic toxicity.…”

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confidence: 99%

Chemical Constituents and Anticancer Effects of the Essential Oil from Leaves of Xylopia laevigata

et al. 2013

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Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential.

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Xylodiol from Xylopia langsdorfiana induces apoptosis in HL60 cells

Cited by 14 publications

References 24 publications

L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway

L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway

Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla

Chemical Constituents and Anticancer Effects of the Essential Oil from Leaves of Xylopia laevigata

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