Natural Products Genomics: A novel approach for the discovery of anti-cancer therapeutics

Li, B.; Gunjan, Samir Kumar; Rogers, Dennis T.; Kulshrestha, Mukul; Falcone, Deane L.; Littleton, John M.

doi:10.1016/j.vascn.2011.04.002

Cited by 10 publications

(6 citation statements)

References 52 publications

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“…There is a continued interest in the investigation of plant extracts for anticancer drug development because of four main reasons. First, plants often produce bioactive compounds that exceed the current capacity of synthetic chemistry 25 , 26 . Second, natural anticancer compounds fit into mechanism-based approach as perfectly as a hand fits into a glove.…”

Section: Introductionmentioning

confidence: 99%

Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells

Khan¹,

Maryam²,

Qazi³

et al. 2015

Int. J. Biol. Sci.

120

119

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Cancer is the second leading cause of deaths worldwide. Despite concerted efforts to improve the current therapies, the prognosis of cancer remains dismal. Highly selective or specific blocking of only one of the signaling pathways has been associated with limited or sporadic responses. Using targeted agents to inhibit multiple signaling pathways has emerged as a new paradigm for anticancer treatment. Icariside II, a flavonol glycoside, is one of the major components of Traditional Chinese Medicine Herba epimedii and possesses multiple biological and pharmacological properties including anti-inflammatory, anti-osteoporosis, anti-oxidant, anti-aging, and anticancer activities. Recently, the anticancer activity of Icariside II has been extensively investigated. Here, in this review, our aim is to give our perspective on the current status of Icariside II, and discuss its natural sources, anticancer activity, molecular targets and the mechanisms of action with specific emphasis on apoptosis pathways which may help the further design and conduct of preclinical and clinical trials.Icariside II has been found to induce apoptosis in various human cancer cell lines of different origin by targeting multiple signaling pathways including STAT3, PI3K/AKT, MAPK/ERK, COX-2/PGE2 and β-Catenin which are frequently deregulated in cancers, suggesting that this collective activity rather than just a single effect may play an important role in developing Icariside II into a potential lead compound for anticancer therapy. This review suggests that Icariside II provides a novel opportunity for treatment of cancers, but additional investigations and clinical trials are still required to fully understand the mechanism of therapeutic effects to further validate it in anti-tumor therapy.

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Section: Introductionmentioning

confidence: 99%

Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells

Khan¹,

Maryam²,

Qazi³

et al. 2015

Int. J. Biol. Sci.

120

119

View full text Add to dashboard Cite

show abstract

“…Four reasons may account for the continued interest in the investigation of phytochemicals for anticancer drug development. First, plants often produce complex bioactive molecules that exceed the current capacity of synthetic organic chemistry [ 8 ]. Second, natural anticancer compounds perfectly fit into a mechanism-based approach.…”

Section: Introductionmentioning

confidence: 99%

Methylferulate from Tamarix aucheriana inhibits growth and enhances chemosensitivity of human colorectal cancer cells: possible mechanism of action

Abaza

Afzal

Al‐Attiyah

et al. 2016

BMC Complement Altern Med

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BackgroundNatural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated. The possible molecular mechanism of MF’s therapeutic efficacy was also assessed.MethodsColumn chromatography and spectral data were used for isolation and identification of MF. MTT, immunofluorescence, flow cytometry, in vitro invasion, fluoremetry, EIA and Real time qPCR were used to measure antiproliferative, chemo-sensitizing effects and other biochemical parameters.ResultsMF showed a dose-dependent anti-proliferative effect on colorectal cancer cells (IC50 = 1.73 – 1.9 mM) with a nonsignificant cytotoxicity toward normal human fibroblast. Colony formation inhibition (P ≤ 0.001, 0.0001) confirmed the growth inhibition by MF. MF arrested cell cycle progression in the S and G2/M phases; induced apoptosis and ROS generation; and inhibited NF-kB DNA-binding activity, proteasomal activities and cell invasion in colorectal cancer cells. MF up-regulated cyclin-dependent kinase inhibitors (p19 INK4D, p21WAF1/CIP1, p27KIP1), pro-apoptotic gene expression (Bax, Bad, Apaf1, Bid, Bim, Smac) and caspases (caspase 2, 3, 6, 7, 8, 9). Moreover, MF down-regulated cyclin-dependent kinases (Cdk1, Cdk2) and anti-apoptotic gene expression (c-IAP-1, c-IAP-2, Bcl2,FLIP). In addition, MF differentially potentiated the sensitivity of colorectal cancer cells to standard chemotherapeutic drugs.ConclusionMF showed a multifaceted anti-proliferative and chemosensitizing effects. These results suggest the chemotherapeutic and co-adjuvant potential of MF.

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“…The A431 cells were cultured in DMEM, supplemented with 10% FBS and 100 U/ml penicillin-streptomycin at 5% CO 2 at a temperature of 37˚C. When they reached 85% confluence, cells were harvested using 0.25% trypsin and then subcultured in flasks measuring 75 cm 2 , as described in the following experiments. Fresh conditioned medium was added every 3 days and subcultures were digested by 0.25% trypsin every 7 or 8 days.…”

Section: Culture Of a Flos-aquaementioning

confidence: 99%

“…Natural products isolated from cyanobacteria have attracted great attention, since they comprise a valuable resource for providing promising drugs for the prevention and treatment of cancer (1,2). Aphanizomenon flos-aquae is a filamentous and heterocytic cyanobacterium (3,4), commonly found in nutrient-rich freshwaters as one of the dominant species in cyanobacterial bloom.…”

Section: Introductionmentioning

confidence: 99%

Extracellular polymeric substance from Aphanizomenon flos-aquae induces apoptosis via the mitochondrial pathway in A431 human epidermoid carcinoma cells

Xue

Liu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Extracellular polymeric substance (EPS) is a substance secreted during algal growth, which has been found to have numerous health-promoting effects. In the present study, A431 human epidermoid carcinoma cells were selected as target cells and cultivated in vitro as an experimental model to investigate the anti-cancer effect of extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) and the possible underlying mechanism. Apoptosis-and cell cycle-associated molecules as well as the mitochondrial membrane potential of the cells were quantified using flow cytometry (FCM). FCM showed that EPS-A induced cell cycle arrest, which led to a loss of mitochondrial function of the A431 cells and an increase in necrotic and late apoptotic cells. In order to evaluate the apoptosis and cell viability, acridine orange/ethidium bromide staining was used, morphological changes were observed using fluorescence microscopy and typical apoptotic characteristics were observed. Following treatment with a high dose of EPS-A, transmission electron microscopy showed nuclear fragmentation, chromosome condensation, cell shrinkage and expansion of the endoplasmic reticulum; apoptotic bodies were also observed. In conclusion, EPS-A caused cell cycle arrest, stimulated cell apoptosis via the mitochondrial pathway and exhibited important anti-cancer activity.

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Natural Products Genomics: A novel approach for the discovery of anti-cancer therapeutics

Cited by 10 publications

References 52 publications

Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells

Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells

Methylferulate from Tamarix aucheriana inhibits growth and enhances chemosensitivity of human colorectal cancer cells: possible mechanism of action

Extracellular polymeric substance from Aphanizomenon flos-aquae induces apoptosis via the mitochondrial pathway in A431 human epidermoid carcinoma cells

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