Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways

Farha, Arakkaveettil Kabeer; Dhanya, S. R.; Mangalam, Sivasankaran Nair; Geetha, B.; Latha, P. G.; Remani, P.

doi:10.1007/s10565-014-9288-z

Cited by 44 publications

(49 citation statements)

References 38 publications

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“…DOE is a well-known sesquiterpene lactone isolated from E. scaber . DOE inhibited the growth of cancer cells in a time- and dose-dependent manner, and these findings are consistent with previous reports that have demonstrated the cytotoxic nature of DOE 16, 17, 18, 19, 20. The cytotoxic activity of a sesquiterpene lactone is attributable to the presence of α-methylene-γ-lactone moiety in the molecule 22 …”

Section: Discussionsupporting

confidence: 91%

“…Deoxyelephantopin (DOE), a sesquiterpne lactone from Elephantopus scaber , exerts many beneficial effects including hepatoprotective, 13 antiprotozoal, 14 and wound healing 15 . DOE has been reported to have anticancer effect 16, 17, 18, 19, 20. The present study was designed to elucidate underlying mechanisms of action of DOE in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Kabeer

Rajalekshmi

Nair

et al. 2017

Integrative Medicine Research

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BackgroundDeoxyelephantopin (DOE) is a natural bioactive sesquiterpene lactone from Elephantopus scaber, a traditionally relevant herb in Chinese and Indian medicine. It has shown promising anticancer effects against a broad spectrum of cancers.MethodsWe examined the effect of DOE on growth, autophagy, apoptosis, cell cycle progression, metastasis, and various molecular signaling pathways in cancer cells, and endeavored to decipher the molecular mechanisms underlying its effect. The cytotoxicity of DOE was examined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and colony formation assays. The antimetastatic potential of DOE was identified by wound closure, as well as invasion and migration assays. The expression of mRNAs and proteins related to cytotoxicity in cancer cells induced by DOE was investigated using reverse transcription-polymerase chain reaction, flow cytometry, and Western blot analysis.ResultsDOE showed significant cytotoxicity and induced apoptosis in cancer cells. DOE promoted the autophagy of HCT 116 and K562 cells. DOE arrested cell cycle progression in the G2/M phase. DOE treatment caused activation of caspase-8, -9, -3 and -7, reactive oxygen species production, and cleavage of cleavage of poly-ADP-ribose polymerase (PARP), the markers of apoptosis. Moreover, apoptosis induction was associated with mitochondrial permeability and endoplasmic reticulum stress. Treatment of cancer cells with DOE inhibited mitogen-activated protein kinases, nuclear factor-kappa B, phosphatidylinositol 3-kinase (PI3K/Akt), and β-catenin signaling. Furthermore, treatment of DOE increased the expression of p53, phospho-Jun amino-terminal kinases (p-JNK), and p-p38 and decreased the expression of phospho-signal transducer and activator of transcription 3 (p-STAT3) and phospho-mammalian target of rapamycin (p-mTOR) in cancer cells. DOE downregulated matrix metalloproteinase (MMP-2) and MMP-9, urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR) mRNA levels in cancer cells.ConclusionThese findings concluded that DOE may be useful as a chemotherapeutic agent against cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Kabeer

Rajalekshmi

Nair

et al. 2017

Integrative Medicine Research

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“…Since DET was reported to induce ROS generation in HepG2 and TS/A cells [10, 12], the ROS levels of MG-63 and U2OS cells were measured after DET exposure. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Deoxyelephantopin Induces Reactive Oxygen Species-Mediated Apoptosis and Autophagy in Human Osteosarcoma Cells

Zou

Zhang

Sun

et al. 2017

Cell Physiol Biochem

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Background/Aims: Osteosarcoma is the predominant form of primary bone malignancy. Although the combinational application of neoadjuvant chemotherapy and surgical resection significantly increases the survival rate, the therapeutic outcome remains unsatisfactory. Deoxyelephantopin (DET), an active ingredient of Elephantopus scaber, has been reported to have an anti-tumor effect in recent publications. This study aimed to investigate whether DET has antineoplastic effects on osteosarcoma cells and its underlying mechanism. Methods: Cell viability and morphological changes were assessed by MTT and Live/dead assays. Cell apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were detected utilizing Annexin V-FITC/PI double staining, DCFH-DA and JC-1 probes, respectively. Autophagy was detected by mRFP-GFP-LC3 adenovirus transfection and western blot. Results: DET dose-dependently reduced the viability of osteosarcoma cells following the increase in intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) reversed this effect. Furthermore, DET induced mitochondrial apoptosis. Depolarized cells were increased, and apoptosis-related proteins, such as Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3 and cleaved ploy ADP-ribose polymerase, were activated. Additionally, we found that DET could induce autophagy in osteosarcoma cells, but autophagy inhibition did not affect the decrease in cell viability. Conclusion: DET induced apoptosis in osteosarcoma cells through ROS generation, mitochondrial dysfunction and caspase activation; in addition, autophagy was involved in the effects of DET on osteosarcoma cells.

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“…Deoxyele phantopin, a sesquiterpene lactone, had been spotted to exhibit antiproliferative and apoptosis-induced properties in SiHa cells. Recently, Farha et al 30 had elucidated the underlying molecular Data were expressed as mean ± SEM of three independent experiments. *Significant difference between control and COP-treated cells as analyzed by two-way ANOVA followed by Bonferroni post; test **p < 0.01 and ***p < 0.001 versus control group.…”

Section: Discussionmentioning

confidence: 99%

Coptisine-induced cell cycle arrest at G2/M phase and reactive oxygen species–dependent mitochondria-mediated apoptosis in non-small-cell lung cancer A549 cells

et al. 2017

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This study aimed to explore the effect of coptisine on non-small-cell lung cancer and its mechanism through various in vitro cellular models (A549). Results claimed significant inhibition of proliferation by coptisine against A549, H460, and H2170 cells with IC 50 values of 18.09, 29.50, and 21.60 µM, respectively. Also, coptisine exhibited upregulation of pH2AX, cell cycle arrest at G2/M phase, and downregulation of the expression of cyclin B1, cdc2, and cdc25C and upregulation of p21 dose dependently. Furthermore, induction of apoptosis in A549 cells by coptisine was characterized by the activation of caspase 9, caspase 8, and caspase 3, and cleavage of poly adenosine diphosphate ribose polymerase. In addition, coptisine was found to increase reactive oxygen species generation, upregulate Bax/Bcl-2 ratio, disrupt mitochondrial membrane potential, and cause cytochrome c release into the cytosol. Besides, treatment with a reactive oxygen species inhibitor (N-acetyl cysteine) abrogated coptisine-induced growth inhibition, apoptosis, reactive oxygen species generation, and mitochondrial dysfunction. Thus, the mediation of reactive oxygen species in the apoptosisinduced effect of coptisine in A549 cells was corroborated. These findings have offered new insights into the effect and mechanisms of action of coptisine against non-small-cell lung cancer.

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Deoxyelephantopin impairs growth of cervical carcinoma SiHa cells and induces apoptosis by targeting multiple molecular signaling pathways

Cited by 44 publications

References 38 publications

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Deoxyelephantopin Induces Reactive Oxygen Species-Mediated Apoptosis and Autophagy in Human Osteosarcoma Cells

Coptisine-induced cell cycle arrest at G2/M phase and reactive oxygen species–dependent mitochondria-mediated apoptosis in non-small-cell lung cancer A549 cells

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