Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway

Zhang, Yu; Bao, Yong; Wu, Yin; Yu, Chun; Huang, Yan; Sun, Yu; Li, Zheng; Li, Yu Xin

doi:10.3892/mmr.2013.1640

Cited by 40 publications

(30 citation statements)

References 34 publications

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“…In the current study, apoptosis was induced in the C2C12 myoblasts only at the 24 h period following exposure to geigerin (Figure 3). Previous studies have reported induction of apoptosis by sesquiterpene lactones in cultured cells (Dirsch, Stuppner & Vollmar 2001; Zhang, Ong & Shen 2004; Zhang et al 2005, 2013). The presence of apoptotic cells was furthermore confirmed by TEM after exposure to geigerin (Figure 5).…”

Section: Discussionmentioning

confidence: 95%

Geigerin-induced cytotoxicity in a murine myoblast cell line (C2C12)

Botha

Clift

Ferreira

et al. 2017

Onderstepoort j. vet. res.

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Geigeria poisoning in sheep, locally known as ‘vermeersiekte’, is an economically important plant poisoning in southern Africa. The toxic principles contained by the toxic plants are believed to be several sesquiterpene lactones, such as geigerin, vermeeric acid and vermeerin, which cause striated muscle lesions in small stock. Because of ethical issues surrounding the use of live animals in toxicity studies, there is currently a dire need to establish an in vitro model that can be used to replace traditional animal experimentation. The objective of this study was to determine the cytotoxicity of geigerin in a murine myoblast cell line (C2C12) using methyl-thiazol-tetrazolium (MTT) and lactate dehydrogenase (LDH) assays, annexin V and propidium iodide (PI) flow cytometry and transmission electron microscopy (TEM). Mouse myoblasts were exposed to 2.0 mM, 2.5 mM and 5.0 mM geigerin for 24, 48 and 72 h. A concentration-dependent cytotoxic response was observed. Apoptosis was detected by means of annexin V flow cytometry during the first 24 h and apoptotic bodies were also visible on TEM. According to the LDH and PI flow cytometry results, myoblast cell membranes were not injured. We concluded that the murine myoblast cell line (C2C12) is a suitable model for future studies planned to evaluate the cytotoxicity of other and combinations of sesquiterpene lactones, with and without metabolic activation, implicated in ‘vermeersiekte’ and to elucidate the subcellular effects of these myotoxins on cultured myoblasts.

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Section: Discussionmentioning

confidence: 95%

Geigerin-induced cytotoxicity in a murine myoblast cell line (C2C12)

Botha

Clift

Ferreira

et al. 2017

Onderstepoort j. vet. res.

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“…Khan et al (15) demonstrated that alantolactone induced cell apoptosis via GSH depletion and ROS generation in glioblastoma cells. Zhang et al (24) reported that alantolactone induced cell apoptosis via ROS generation in RKO cells.…”

Section: Discussionmentioning

confidence: 99%

Alantolactone induces apoptosis of human cervical cancer cells via reactive oxygen species generation, glutathione depletion and inhibition of the Bcl-2/Bax signaling pathway

Jiang

Wang

2016

Oncology Letters

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Abstract.Alantolactone is the active ingredient in frankincense, and is extracted from the dry root of elecampane. It has a wide variety of uses, including as an insect repellent, antibacterial, antidiuretic, analgesic and anticancer agent. In addition, alantolactone induces apoptosis of human cervical cancer cells, however, its mechanism of action remains to be elucidated. Therefore, the present study investigated whether alantolactone was able to induce apoptosis of human cervical cancer cells, and its potential mechanisms of action were analyzed. Treatment of HeLa cells with alantolactone (0, 10, 20, 30, 40, 50 and 60 µM) for 12 h significantly inhibited growth in a dose-dependent manner. Cells treated with 30 µM of alantolactone for 0, 3, 6 and 12 h demonstrated marked induction of apoptosis in a time-dependent manner. Treatment of HeLa cells with 30 µM of alantolactone for 0, 3, 6 and 12 h significantly induced the generation of reactive oxygen species (ROS) and inhibited glutathione (GSH) production in HeLa cells in a dose-dependent manner. Alantolactone additionally markedly inhibited the Bcl-2/Bax signaling pathway in HeLa cells. Therefore, administration of alantolactone induced apoptosis of human cervical cancer cells via ROS generation, GSH depletion and inhibition of the Bcl-2/Bax signaling pathway.

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“…These are the death receptor pathway and the mitochondria pathway [1-3]. Caspases, a family of cysteine proteases, play a critical role in apoptosis [4]. In addition, mitochondrial-dependent apoptosis is regulated principally by the Bcl-2 family proteins, such as Bax, Bcl-2 and Bak [5].…”

Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

Dong

Yin

et al. 2017

Cell Physiol Biochem

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Background/Aims: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. Methods: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were determined by flow cytometry, while the expression of apoptosis-related proteins was determined by Western blot analysis. Results: Treatment with aloe-emodin significantly reduced cell viability and induced apoptosis in HepaRG cells in a dose- and time-dependent manner. It provoked ROS generation and depolarization of MMP in HepaRG cells when compared with controls. Aloe-emodin dose-dependently increased release of mitochondrial cytochrome c, and levels of Fas, p53, p21, Bax/Bcl-2 ratio, as well as activation of caspase-3, caspase-8, caspase-9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). It also induced S-phase cell cycle arrest by increasing the expression of p21 and cyclin E proteins while significantly decreasing the expression of cyclin A and CDK2. Conclusion: These results suggest that aloe-emodin inhibits cell proliferation and induces apoptosis in HepaRG cells, most probably through a mechanism involving both Fas death pathway and the mitochondrial pathway by generation of ROS. These findings underscore the need for risk assessment of human exposure to aloe-emodin.

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Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway

Cited by 40 publications

References 34 publications

Geigerin-induced cytotoxicity in a murine myoblast cell line (C2C12)

Geigerin-induced cytotoxicity in a murine myoblast cell line (C2C12)

Alantolactone induces apoptosis of human cervical cancer cells via reactive oxygen species generation, glutathione depletion and inhibition of the Bcl-2/Bax signaling pathway

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

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