Bioassay-guided isolation of a sesquiterpene lactone of deoxyelephantopin from Elephantopus scaber Linn. active on Trypanosome brucei rhodesience

Zahari, Zuriati; Jani, Nor Akmalazura; Amanah, Azimah; Latif, Mohd Naffidi Abdul; Majid, Mohamed Isa Abdul; Adenan, Mohd Ilham

doi:10.1016/j.phymed.2013.09.011

Cited by 21 publications

(13 citation statements)

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“…This often acts as a Michael acceptor for nucleophiles such as the thiol group commonly found in the target protein and enzyme (Kupchan et al, 1971;Lee et al, 1971;Picman, 1986). Biological activities, such as hepatoprotective (Huang et al, 2013), antitrypanosomal (Zahari et al, 2014), and anti-cancer cell activities (Farha et al, 2014;Geetha et al, 2012;Kabeer et al, 2013;Lee et al, 2010;Lee and Shyur, 2012;Su et al, 2011;Zou et al, 2008) have been reported for plant sesquiterpene lactones. Our recent studies have also revealed that DET possesses potent activity against TS/A (ERþ) mammary tumor growth and metastasis in syngeneic mice through inhibiting m-calpain activity and induction of centrosomal ubiquitinated protein aggregates, protein carbonylation and ER stress-mediated apoptosis that led to significant attenuation of cancer cell motility and metastasis (Huang et al, 2010;Lee et al, 2010;Lee and Shyur, 2012).…”

Section: Introductionmentioning

confidence: 99%

Novel sesquiterpene lactone analogues as potent anti‐breast cancer agents

et al. 2016

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Triple-negative breast cancer (TNBC) is associated with high grade, metastatic phenotype, younger patient age, and poor prognosis. The discovery of an effective anti-TNBC agent has been a challenge in oncology. In this study, fifty-eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD-35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA-MB-231, without inhibiting normal mammary cells M10. DETD-35 exhibited a better effect than parental DET on inhibiting migration, invasion, and motility of MDA-MB-231 cells in a concentration-dependent manner. Comparative study of DETD-35, DET and chemotherapeutic drug paclitaxel (PTX) showed that PTX mainly caused a typical time-dependent G2/M cell-cycle arrest, while DETD-35 or DET treatment induced cell apoptosis. In vivo efficacy of DETD-35 was evaluated using a lung metastatic MDA-MB-231 xenograft mouse model. DETD-35 significantly suppressed metastatic pulmonary foci information along with the expression level of VEGF and COX-2 in SCID mice. DETD-35 also showed a synergistic antitumor effect with PTX in vitro and in vivo. This study suggests that the novel compound DETD-35 may have a potential to be further developed into a therapeutic or adjuvant agent for chemotherapy against metastatic TNBC.

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Section: Introductionmentioning

confidence: 99%

Novel sesquiterpene lactone analogues as potent anti‐breast cancer agents

et al. 2016

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“…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.…”

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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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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“…The sesquiterpene lactone compounds, DET and IDET, are major components of Elephantopus scaber and Elephantopus carolinianus which belong to the family Asteraceae [ 16 , 17 , 18 ]. Elephantopus scaber Linn, a medicinal plant of the Asteraceae family, is commonly known as “elephant’s food” in English, “tutup bumi” in Malaysian, “didancao” in Chinese, and “gobhi” in Hindi [ 19 , 20 , 21 ]. The herb is widely distributed all over the world especially in East Asia, Southeast Asia, Africa, Australia, India, and South America [ 20 , 21 , 22 ].…”

Section: Natural Sources and Biological Activitiesmentioning

confidence: 99%

Deoxyelephantopin and Isodeoxyelephantopin as Potential Anticancer Agents with Effects on Multiple Signaling Pathways

et al. 2017

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Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of “Elephantopus scaber and Elephantopus carolinianus”, traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation. Recently, the anticancer activity of DET and IDET has been widely investigated. Here, our aim is to review the current status of DET and IDET, and discuss their anticancer activity with specific emphasis on molecular targets and mechanisms used by these compounds to trigger apoptosis pathways which may help to further design and conduct research to develop them as lead therapeutic drugs for cancer treatments. The literature has shown that DET and IDET induce apoptosis through multiple signaling pathways which are deregulated in cancer cells and suggested that by targeting multiple pathways simultaneously, these compounds could selectively kill cancer cells. This review suggests that DET and IDET hold promising anticancer activity but additional studies and clinical trials are needed to validate and understand their therapeutic effect to develop them into potent therapeutics for the treatment of cancer.

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Bioassay-guided isolation of a sesquiterpene lactone of deoxyelephantopin from Elephantopus scaber Linn. active on Trypanosome brucei rhodesience

Cited by 21 publications

References 32 publications

Novel sesquiterpene lactone analogues as potent anti‐breast cancer agents

Novel sesquiterpene lactone analogues as potent anti‐breast cancer agents

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Deoxyelephantopin and Isodeoxyelephantopin as Potential Anticancer Agents with Effects on Multiple Signaling Pathways

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