Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28

Wong, Pooi-Fong; Cheong, Wei-Fun; Shu, Meng-Hooi; Teh, Chin-Hoe; Chan, Kit‐Lam; AbuBakar, Sazaly

doi:10.1016/j.phymed.2011.07.001

Cited by 62 publications

(52 citation statements)

References 30 publications

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“…Natural-product based drugs are gaining their popularity as preventive medicines or for health management, and hence this has spurred an intensive search for bioactive plant-derived anticancer compounds [15]. The genus Phyllanthus is one of the most widely distributed plants throughout the Amazon rainforests as well as other tropical and subtropical regions.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Raf-MEK-ERK and Hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line

Lee

Jaganath

Manikam

et al. 2013

BMC Complement Altern Med

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BackgroundLung cancer constitutes one of the malignancies with the greatest incidence and mortality rates with 1.6 million new cases and 1.4 million deaths each year. Prognosis remains poor due to deleterious development of multidrug resistance resulting in less than 15% lung cancer patients reaching five years survival. We have previously shown that Phyllanthus induced apoptosis in conjunction with its antimetastastic action. In the current study, we aimed to determine the signaling pathways utilized by Phyllanthus to exert its antimetastatic activities.MethodsCancer 10-pathway reporter array was performed to screen the pathways affected by Phyllanthus in lung carcinoma cell line (A549) to exert its antimetastatic effects. Results from this array were then confirmed with western blotting, cell cycle analysis, zymography technique, and cell based ELISA assay for human total iNOS. Two-dimensional gel electrophoresis was subsequently carried out to study the differential protein expressions in A549 after treatment with Phyllanthus.ResultsPhyllanthus was observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via suppression of Raf protein. Inhibition of this pathway resulted in the suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis. Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1α that led to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of proteins downregulated by Phyllanthus that were involved in metastatic processes, including invasion and mobility proteins (cytoskeletal proteins), transcriptional proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species tested, P. urinaria showed the greatest antimetastatic activity.ConclusionsPhyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways that led to suppression of various critical proteins for A549 invasion and migration.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Raf-MEK-ERK and Hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line

Lee

Jaganath

Manikam

et al. 2013

BMC Complement Altern Med

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“…Eurycomanone is cytotoxic to HepG2 cells and induces apoptosis through the up-regulation of p53 and Bax, and downregulation of Bcl-2 (Mahfudh and Pihie, 2008;Zakaria et al, 2009). Eurycomanone exhibits pro-apoptotic, anti-proliferative and anticlonogenic cell growth effects and suppression of the tumor markers and several known cancer cell growth-associated genes (Wong et al, 2012;Zakaria et al, 2009). In general, quassinoids and their derivatives possess promising antiangiogenic properties (Wong et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Eurycomanone exhibits pro-apoptotic, anti-proliferative and anticlonogenic cell growth effects and suppression of the tumor markers and several known cancer cell growth-associated genes (Wong et al, 2012;Zakaria et al, 2009). In general, quassinoids and their derivatives possess promising antiangiogenic properties (Wong et al, 2012). Furthermore, quassinoids are capable of inducing an array of biological responses (Fukamiya et al, 2005;Salamah et al, 2009) including inhibition of protein synthesis (Cuendet, and Pezzuto, 2004;Liao et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function

Al-Salahi

Chan

Majid

et al. 2013

Microvascular Research

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“…Among the isolates, 9, 10-dimethoxycanthin-6-one, 10-hydroxy-9-methoxycanthin-6-one and dihydroniloticin, showed strong toxicity and an isolate, 14-deacetyleurylene displayed stronger activity than standard drug, the Fluorouracil. Wong et al (2012) studied the effect of eurycomanone on lung cancer cells (A549) proliferation, clonogenic cell growth, expression of lung cancer markers and cancer related genes. The result showed that eurycomanone inhibited lung cancer cell proliferation in a dose dependent manner in a concentration ranging from 5 to 20 µg mLG 1 and the concentration that inhibited 50% cell growth was 5.1 µg mLG 1 .…”

Section: Anti-cancer Effectmentioning

confidence: 99%

Review on Eurycoma longifolia Pharmacological and Phytochemical Properties

Mohamed¹,

Vejayan²,

Yusoff³

2015

J. of Applied Sciences

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A B S T R A C TEurycoma longifolia or Tongkat Ali is famous for its aphrodisiac property and the traditional uses range from tonic after childbirth to treating malaria. Phytochemical studies revealed the presence of bioactive compounds such as quassinoids, alkaloids, squalene derivatives, tirucallane-type triterpenes and biphenylneolignans. Existing research revealed that plant has potential to treat various diseases and to replace the current treatment. Purpose of this article is to evaluate and summarize the existing literatures concerning phytochemical, biological and toxicological studies of E. longifolia. It is expected that critical evaluation will be useful for researchers working on the potential role of E. longifolia in treating diseases or for product development.

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Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28

Cited by 62 publications

References 30 publications

Inhibition of Raf-MEK-ERK and Hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line

Inhibition of Raf-MEK-ERK and Hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line

Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function

Review on Eurycoma longifolia Pharmacological and Phytochemical Properties

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