The in vitro study of apoptosis in NB4 cell induced by citral

Xia, Hailong; Liang, Wei; Qin, Song; Chen, Xiaowen; Chen, Xin; Hong, Jian

doi:10.1007/s10616-012-9453-2

Cited by 43 publications

(24 citation statements)

References 16 publications

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“…A major hurdle in the use of citral as an anti-cancer therapeutic is the lack of understanding of the mechanism by which this monoterpenoid induces cancer cell death. While previous reports have demonstrated an increase in cleaved caspase-3 in cancer cells treated with citral34, the upstream mechanisms that result in the activation of this apoptosis-mediating caspase in these experiments are unclear.…”

mentioning

confidence: 73%

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Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation

Kapur

Felder

Fass

et al. 2016

Sci Rep

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The monoterpenoid, citral, when delivered through PEG-b-PCL nanoparticles inhibits in vivo growth of 4T1 breast tumors. Here, we show that citral inhibits proliferation of multiple human cancer cell lines. In p53 expressing ECC-1 and OVCAR-3 but not in p53-deficient SKOV-3 cells, citral induces G1/S cell cycle arrest and apoptosis as determined by Annexin V staining and increased cleaved caspase3 and Bax and decreased Bcl-2. In SKOV-3 cells, citral induces the ER stress markers CHOP, GADD45, EDEM, ATF4, Hsp90, ATG5, and phospho-eIF2α. The molecular chaperone 4-phenylbutyric acid attenuates citral activity in SKOV-3 but not in ECC-1 and OVCAR-3 cells. In p53-expressing cells, citral increases phosphorylation of serine-15 of p53. Activation of p53 increases Bax, PUMA, and NOXA expression. Inhibition of p53 by pifithrin-α, attenuates citral-mediated apoptosis. Citral increases intracellular oxygen radicals and this leads to activation of p53. Inhibition of glutathione synthesis by L-buthionine sulfoxamine increases potency of citral. Pretreatment with N-acetylcysteine decreases phosphorylation of p53 in citral-treated ECC-1 and OVCAR-3. These results define a p53-dependent, and in the absence of p53, ER stress-dependent mode of action of citral. This study indicates that citral in PEG-b-PCL nanoparticle formulation should be considered for treatment of breast and other tumors.

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mentioning

confidence: 73%

“…In vitro studies have reported on the ability of citral to induce cell death of breast cancer as well as leukemia cells34. In a model for chemically-induced skin cancer, chronic application of citral resulted in a decrease in the number of animals developing tumors5.…”

mentioning

confidence: 99%

Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation

Kapur

Felder

Fass

et al. 2016

Sci Rep

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“…In fact, suppression of NF-jB activity has become an interesting approach to render cancer cells more susceptible to chemotherapy (Karin et al, 2002). A recent study in leukemic NB4 cells illustrated that an inhibition of NF-jB protein involved in apoptotic effects of citral on these cells (Xia et al, 2013). It may be possible that citral may exert potentiating activity by this manner but this hypothesis needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it inhibited human breast cancer cell MCF-7 growth and induced cycle arrest in G2/M phase (Chaouki et al, 2009). Recently, Xia et al (2013) found that citral has apoptotic activity on acute promyelocytic leukemia cell lines (NB4 cells) and this effect was attributed to the activation of caspase-3 and down-regulation of nuclear factor kappa B (NF-jB) expression. Similarly, previous work from our laboratory have found that citral induced human lymphoma Ramos cell apoptosis by activating caspase activity in a concentration and time-dependent manner but has no effect on cell distribution in the cell cycle (unpublished observation).…”

Section: Introductionmentioning

confidence: 99%

Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells

Dangkong

Limpanasithikul

2014

Pharmaceutical Biology

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Context: Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass. Objectives: We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells. Materials and methods: Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 mM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR. Results: Citral had cytotoxicity on cells with an IC 50 value of 77.19 ± 4.95 mM. Citral at concentrations of 10, 20, and 40 mM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC 50 (mM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 mM) in combination with doxorubicin (1.5 mM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of antiapoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug. Discussion and conclusion: Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.

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“…Por tanto, la capacidad de los terpenos para inducir la muerte celular programada, es de gran interés oncológico (8)(9)(10).…”

Section: Introduccciónunclassified

Linalool effect on mitochondrial bioenergetics rat liver

Bueno-Duarte

Méndez‐Sánchez

2015

Vitae

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RESUMENAntecedentes: El linalool (2,6-dimetil-2,7-octadien-6-ol) es un monoterpeno presente en más de 200 tipos de plantas, y constituye el componente mayoritario de varios aceites esenciales. El linalool posee una amplia variedad de potenciales propiedades farmacológicas; que van desde propiedades antisépticas, ansiolíticas, anti-inflamatorias, antifúngicas, antimicrobianas y proapotóticas en diferentes líneas de cé-lulas tumorales. Sin embargo, su principal uso está relacionado como una molécula odorante o fragancia en productos de uso tópico en productos cosméticos y en la industria del perfume. Objetivo: En este estudio se evaluó el efecto del linalool sobre la bioenergética de mitocondrias aisladas de hígado de rata. Métodos: El linalool en concentraciones entre (5-100μg/mL) fue evaluado en mitocondrias aisladas de ratas machos albinas raza Wistar, de acuerdo al método descrito por Voss et al (1961). Inicialmente, se determinó el consumo de oxígeno en mitocondrias intactas mediante un método polarográfico por medio de un oxígrafo. Posteriormente, se determinó el efecto del compuesto sobre las enzimas de la cadena respiratoria mitocondrial usando métodos polarográficos y espectrofotométricos. Resultados: Los resultados obtenidos indican que el linalool en las concentraciones de 5, 10, 50 y 100μg/mL, afecta la velocidad de consumo de oxígeno en el estado 3 y 4 de mitocondrias energizadas con glutamato-malato y succinato. Sin embargo, el efecto inhibitorio es mayor al usar glutamato-malato como sustrato. Por su parte, el análisis de la actividad de las enzimas de la cadena respiratoria mitocondrial mostró que el linalool (50μg/mL) inhibe los complejos I, III y la actividad ATPasa. Conclusiones: El linalool inhibe el complejo I, complejo III y la ATPasa, esta inhibición podría aumentar la generación de especies reactivas de oxígeno.Palabras clave: Linalool, mitocondria, enzimas, consumo de oxígeno. ABSTRACTBacground: The linalool (2,6-dimethyl-2 ,7-octadiene-6-ol) is a monoterpene present in more than 200 types of plants, and it is the major component of several essential oils. The linalool has a wide range of potential pharmacological properties, such as antiseptic, anxiolytic, anti-inflammatory, antifungal, antimicrobial and proapoptotic in different tumor cell lines. However, its primary use is associated as

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The in vitro study of apoptosis in NB4 cell induced by citral

Cited by 43 publications

References 16 publications

Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation

Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation

Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells

Linalool effect on mitochondrial bioenergetics rat liver

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