Antineoplastic effects of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, on lung adenocarcinoma (A549) cells

Kabeer, Farha Arakkaveettil; Sreedevi, Geetha B.; Nair, Mangalam S.; Rajalekshmi, Dhanya Sethumadhavan; Gopalakrishnan, Latha P.; Sujathan, K.; Remani, P.

doi:10.3736/jintegrmed2013040

Cited by 39 publications

(29 citation statements)

References 26 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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“…Notably, DET is also observed to be superior to paclitaxel (PTX) in prolonging the lifespan/survival rate in TS/A mammary tumor isograft bearing mice (19). In addition, DET has been reported to possess anti-lung adenocarcinoma (23), nasopharyngeal carcinoma (24) and human lymphocyte proliferation in vitro and anti-ascites tumor in vivo (25). Together, we consider DET as a novel lead compound for further modification or optimization of its structure to create a more potent drug lead for cancer management.…”

Section: Introductionmentioning

confidence: 99%

A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice

Feng

Nakagawa‐Goto

Lee

et al. 2016

Molecular Cancer Therapeutics

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Acquired resistance to vemurafenib develops through reactivation of RAF/MEK/ERK signaling or bypass mechanisms. Recent combination therapies such as a MEK inhibitor combined with vemurafenib show improvement in major clinical end points but the percentage of patients with adverse toxic events is higher than with vemurafenib monotherapy and most patients ultimately relapse. Therefore, there is an urgent need to develop new anti-melanoma drugs and/or adjuvant agents for vemurafenib therapy. In this study, we created a novel semi-organically modified derivative, DETD-35, from deoxyelephantopin (DET), a plant sesquiterpene lactone demonstrated as an anti-inflammatory and anti-mammary tumor agent. Our results show that DETD-35 inhibited proliferation of a panel of melanoma cell lines, including acquired vemurafenib resistance A375 cells (A375-R) established in this study, with superior activities to DET and no cytotoxicity to normal melanocytes. DETD-35 suppressed tumor growth and reduced tumor mass as effectively as vemurafenib in A375 xenograft study. Furthermore, DETD-35 also reduced tumor growth in both acquired (A375-R) and intrinsic (A2058) vemurafenib resistance xenograft models, where vemurafenib showed no anti-tumor activity. Notably, the combination of DETD-35 and vemurafenib exhibited the most significant effects in both in vitro and in vivo xenograft studies due to synergism of the compound and the drug. Mechanistic studies suggested that DETD-35 overcame acquired vemurafenib resistance at least in part through deregulating MEK-ERK, Akt, and STAT3 signaling pathways and promoting apoptosis of cancer cells. Overall, our results suggest that DETD-35 may be useful as a therapeutic or adjuvant agent against BRAFV600E mutant and acquired vemurafenib resistance melanoma.

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“…These results indicate that CGII induces caspase-dependent apoptosis through both the intrinsic and extrinsic pathways. Indeed, growing evidence has suggested that cytotoxic natural compounds have the ability to inhibit malignant cell growth by cell cycle arrest and by induction of apoptosis through both extrinsic and intrinsic pathways [24]. The induction of caspase-dependent apoptosis by CGII was further confirmed by the pan-caspase inhibitor z-VAD-fmk, which partially reduced the CGII-induced loss of cell viability in SGC-7901 cells.…”

Section: Discussionmentioning

confidence: 97%

A C₂₁-Steroidal Glycoside Isolated from the Roots ofCynanchum auriculatumInduces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells

Wang

Zhang

Hong

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Caudatin 3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside (CGII) is one of the C21-steroidal glycosides isolated from the roots of Cynanchum auriculatum ROYLE ex WIGHT. This study aimed to determine the cell growth, cell proliferation, and apoptotic cell death of human gastric cancer cells after CGII treatment. MTT assay was used to determine cell growth; fluorescence-activated cell sorting analysis was used to evaluate cell cycle distribution and apoptotic cell death. Immunoblotting was applied for measuring the expression of proteins involved in the cell cycle progression. The activities of caspase-3, -8, and -9 were detected by colorimetric caspase activity assays. CGII inhibited cell growth of human gastric cancer SGC-7901 cells in a concentration- and time-dependent manner. Treatment of SGC-7901 cells with CGII resulted in G1 phase cell cycle arrest, accompanied with decreased expression of cyclin D1 and cyclin-dependent kinases 4 and 6. CGII induced cell apoptosis and activated caspase-3, caspase-8, and caspase-9. In contrast, pan-caspase inhibitor z-VAD-fmk partially abolished the CGII-induced growth inhibition of SGC-7901 cells. In conclusion, CGII inhibits cell growth of human gastric cancer cells by inducing G1 phase cell cycle arrest and caspase-dependent apoptosis cascades.

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Antineoplastic effects of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, on lung adenocarcinoma (A549) cells

Cited by 39 publications

References 26 publications

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice

A C₂₁-Steroidal Glycoside Isolated from the Roots ofCynanchum auriculatumInduces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells

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Antineoplastic effects of deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber, on lung adenocarcinoma (A549) cells

Cited by 39 publications

References 26 publications

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

A Novel Plant Sesquiterpene Lactone Derivative, DETD-35, Suppresses BRAFV600E Mutant Melanoma Growth and Overcomes Acquired Vemurafenib Resistance in Mice

A C21-Steroidal Glycoside Isolated from the Roots ofCynanchum auriculatumInduces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells

Contact Info

Product

Resources

About

A C₂₁-Steroidal Glycoside Isolated from the Roots ofCynanchum auriculatumInduces Cell Cycle Arrest and Apoptosis in Human Gastric Cancer SGC-7901 Cells