Chloroform Fraction of<i>Centratherum anthelminticum</i>(L.) Seed Inhibits Tumor Necrosis Factor Alpha and Exhibits Pleotropic Bioactivities: Inhibitory Role in Human Tumor Cells

Arya, Aditya; Achoui, Mouna; Cheah, Shiau‐Chuen; Abdelwahab, Siddig Ibrahim; Narrima, Putri; Mohan, Syam; Mustafa, Mohd Rais; Mohd, Mustafa Ali

doi:10.1155/2012/627256

Cited by 18 publications

(11 citation statements)

References 39 publications

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“…Then the dried fractions were kept at −20°C until further use. In our previous paper, the chloroform extract (CACF) showed highest activity on MTT assay, therefore CACF was chosen for this study [23].…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported that the chloroform, but not hexane or methanol fractions from C. anthelminticum (L.) seeds (CACF) exhibited anti-oxidant property by inhibiting tumor necrosis factor-α (TNF-α)-induced human cancer cell growth by interrupting the activation of nuclear factor-kappa B (NF-κB) [23]. However, the active compounds in CACF were not examined in the previous reports.…”

Section: Introductionmentioning

confidence: 99%

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Induction of Apoptosis in Human Breast Cancer Cells via Caspase Pathway by Vernodalin Isolated from Centratherum anthelminticum (L.) Seeds

et al. 2013

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Background Centratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-α (TNF-α)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously.Methodology/Principal FindingsIn this study, we showed that CACF inhibited growth of MCF-7 human breast cancer cells. CACF induced apoptosis in MCF-7 cells as marked by cell size shrinkage, deformed cytoskeletal structure and DNA fragmentation. To identify the cytotoxic compound, CACF was subjected to bioassay-guided fractionation which yielded 6 fractions. CACF fraction A and B (CACF-A, -B) demonstrated highest activity among all the fractions. Further HPLC isolation, NMR and LC-MS analysis of CACF-A led to identification of vernodalin as the cytotoxic agent in CACF-A, and -B. 12,13-dihydroxyoleic acid, another major compound in CACF-C fraction was isolated for the first time from Centratherum anthelminticum (L.) seeds but showed no cytotoxic effect against MCF-7 cells. Vernodalin inhibited cell growth of human breast cancer cells MCF-7 and MDA-MB-231 by induction of cell cycle arrest and apoptosis. Increased of reactive oxygen species (ROS) production, coupled with downregulation of anti-apoptotic molecules (Bcl-2, Bcl-xL) led to reduction of mitochondrial membrane potential (MMP) and release of cytochrome c in both human breast cancer cells treated with vernodalin. Release of cytochrome c from mitochondria to cytosol triggered activation of caspase cascade, PARP cleavage, DNA damage and eventually cell death.Conclusions/SignificanceTo the best of our knowledge, this is the first comprehensive study on cytotoxic and apoptotic mechanism of vernodalin isolated from the Centratherum anthelminticum (L.) seeds in human breast cancer cells. Overall, our data suggest a potential therapeutic value of vernodalin to be further developed as new anti-cancer drug.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis in Human Breast Cancer Cells via Caspase Pathway by Vernodalin Isolated from Centratherum anthelminticum (L.) Seeds

et al. 2013

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“…We recently reported that CACF inhibited the growth of breast cancer cell lines [17]; however, its effect and detailed mechanism on skin cancer is yet to be investigated. Hence, the aim of this study is to evaluate the therapeutic effect of CACF and the cellular mechanism underlying the anti-cancer effect on melanoma malignancy.…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways

Looi

Moharram

Paydar

et al. 2013

BMC Complement Altern Med

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BackgroundCentratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called “Kayakalp”, commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.MethodsA chloroform fraction was extracted from C. anthelminticum (CACF). Bioactive compounds of the CACF were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Human melanoma cell line A375 was treated with CACF in vitro. Effects of CACF on growth inhibition, morphology, stress and survival of the cell were examined with MTT, high content screening (HSC) array scan and flow cytometry analyses. Involvement of intrinsic or extrinsic pathways in the CACF-induced A375 cell death mechanism was examined using a caspase luminescence assay. The results were further verified with different caspase inhibitors. In addition, Western blot analysis was performed to elucidate the changes in apoptosis-associated molecules. Finally, the effect of CACF on the NF-κB nuclear translocation ability was assayed.ResultsThe MTT assay showed that CACF dose-dependently inhibited cell growth of A375, while exerted less cytotoxic effect on normal primary epithelial melanocytes. We demonstrated that CACF induced cell growth inhibition through apoptosis, as evidenced by cell shrinkage, increased annexin V staining and formation of membrane blebs. CACF treatment also resulted in higher reactive oxygen species (ROS) production and lower Bcl-2 expression, leading to decrease mitochondrial membrane potential (MMP). Disruption of the MMP facilitated the release of mitochondrial cytochrome c, which activates caspase-9 and downstream caspase-3/7, resulting in DNA fragmentation and up-regulation of p53 in melanoma cells. Moreover, CACF prevented TNF-α-induced NF-κB nuclear translocation, which further committed A375 cells toward apoptosis.ConclusionsTogether, our findings suggest CACF as a potential therapeutic agent against human melanoma malignancy.

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“…The observed liver regenerating ability of ESEt in the present study might be by inhibiting the factors that hindered liver tissue regeneration like tumor necrosis factor alpha (TNFα), etc (Kang et al, 2012). Amazingly, chloroform fraction of C. anthelminticum seeds was claimed to inhibit TNF-α in human tumor cells (Arya et al, 2012).…”

Section: Discussionmentioning

confidence: 54%

Centratherum anthelminticum seeds reverse the carbon tetrachloride-induced hepatotoxicity in rats

Qureshi¹,

Rais²,

Usmani³

et al. 2016

Afr. J. Pharm. Pharmacol.

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The present study is the first attempt to evaluate the hepatoprotective effect of ethanolic seeds extract (ESEt) of Centratherum anthelminticum (black cumin) in carbon tetrachloride (CCl 4)-induced liver injury. The test doses (600 and 800 mg/kg) of same extract were found effective in their respective test groups by improving the body and liver weights, serum alanine and aspartate transaminases, γglutamyltranspeptidase, alkaline phosphatase, total proteins, albumin, total bilirubin, especially indirect bilirubin and uric acid levels as compared to CCl 4-induced hepatotoxic control group. In addition, decreased percent inhibitions of antioxidant parameters including catalase, superoxide dismutase and reduced glutathione accompanied with increased percent inhibition of lipid peroxidation observed in both test groups. Histopathological studies also proved the liver regenerating property of ESEt by showing decrease in fatty deposition, necrosis and inflammation around the central vein of liver lobules. Therefore, the ESEt was found to be hepatoprotective and antioxidative in nature.

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Chloroform Fraction ofCentratherum anthelminticum(L.) Seed Inhibits Tumor Necrosis Factor Alpha and Exhibits Pleotropic Bioactivities: Inhibitory Role in Human Tumor Cells

Cited by 18 publications

References 39 publications

Induction of Apoptosis in Human Breast Cancer Cells via Caspase Pathway by Vernodalin Isolated from Centratherum anthelminticum (L.) Seeds

Induction of Apoptosis in Human Breast Cancer Cells via Caspase Pathway by Vernodalin Isolated from Centratherum anthelminticum (L.) Seeds

Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways

Centratherum anthelminticum seeds reverse the carbon tetrachloride-induced hepatotoxicity in rats

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