Antiausterity Agents from <i>Uvaria dac</i> and Their Preferential Cytotoxic Activity against Human Pancreatic Cancer Cell Lines in a Nutrient-Deprived Condition

Awale, Suresh; Ueda, Junichi; Athikomkulchai, Sirivan; Abdelhamed, Sherif; Yokoyama, Satoru; Saiki, Ikuo; Miyatake, Ryuta

doi:10.1021/np300295h

Cited by 43 publications

(27 citation statements)

References 32 publications

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“…Among the 5 plant extracts sensitizing breast cancer cells to TRAIL, U. dac and its active constituent (+) grandifloracin showed anti-austerity activity against PANC-1 human pancreatic cancer cells in a nutrition-deficient tumor-mimicking environment (18). The extract of A. vulgaris has been reported to have cytotoxicity against MCF-7 cells (19).…”

Section: Discussionmentioning

confidence: 99%

Identification of plant extracts sensitizing breast cancer cells to TRAIL

et al. 2013

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Abstract. Triple-negative breast cancer (TNBC) is an aggressive heterogeneous cancer subgroup with a higher rate of distant recurrence and a poorer prognosis compared to other subgroups. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive molecule that induces cell death in various tumor cells without causing cytotoxicity to normal cells; however, primary or acquired resistance to TRAIL often limits its efficacy in cancer patients. To develop combination therapies to improve TRAIL efficacy and/or to overcome the resistant mechanism, we screened 138 medicinal plant extracts against TRAIL-sensitive and -insensitive TNBC cell lines, MDA-MB-231 and MDA-MB-468. Among them, 5 plant extracts, Uvaria dac, Artemisia vulgaris, Cortia depressa, Dichasia bengalensis and Cinnamomum obtusifolium did not cause apparent cytotoxicity (<20%) as a single regimen, but showed significant synergistic effects in combination with TRAIL against both cell lines. Moreover, Uvaria dac, Artemisia vulgaris and Cinnamomum obtusifolium were found to suppress the phosphorylation of p65 that is involved in TRAIL-resistant mechanisms. These observations suggest that the identified plant extracts in combination with TRAIL could lead to potential therapeutic benefits for cancer patients in the clinical setting. IntroductionBreast cancer is one of the most frequently diagnosed types of cancer and is also the leading cause of cancer-related mortality among women, representing 23% of total cancer cases and 14% of cancer-related mortality (1). Breast cancer is classified into different categories according to the expression of three receptors, estrogen receptor (ER), progesterone receptor (PR), and HER2/Neu (2). A triple-negative breast cancer (TNBC), which is ER-negative, PR-negative, and HER2-negative, is one of the most aggressive forms that accounts for 15-25% of all breast cancer cases and is associated with a poor prognosis and unresponsiveness to the usual endocrine therapies (3-5).The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate apoptosis via the activation of death receptor 4 (DR4) and death receptor 5 (DR5). As TRAIL can selectively induce apoptosis in cancer cells, including breast cancer cells, without causing toxicity to normal cells (6-8), it could be a safe medication for cancer patients; however, primary or acquired resistance to TRAIL is often observed which may limit its efficacy in cancer patients (6). Therefore, increasing TRAIL efficacy by combining with natural medicines or other chemotherapeutic agents is an important strategy in the treatment of breast cancer in the clinical setting. We previously identified that vanillin, an active constituent of vanilla, enhances TRAIL-induced apoptosis in cancer cells via suppression of NF-κB (9). This finding prompted us to search for other natural products that can sensitize cancer cells to TRAIL or that can overcome the TRAIL-resistant mechanism.In the present study, we screened 138 medicin...

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Section: Discussionmentioning

confidence: 99%

Identification of plant extracts sensitizing breast cancer cells to TRAIL

et al. 2013

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“…Over 130 compounds are identified in various organs of the tree of A. altilis, more than 70 of which derived from the phenylpropanoid pathway, including a number of prenylated dihydrochalcones [16][17][18][19][20][21][22][23][24][25], prenylated flavonoids [21][22][23][25][26][27][28][29][30][31][32], and prenylated aurones [25,33] together with some triterpenoids and phenolic compounds [34][35][36][37] ( Fig. 1-4).…”

Section: Chemical Constituents Of a Altilismentioning

confidence: 99%

“…Based on this strategy, many reports demonstrated that there were many natural products possessed antiausterity activity from medicinal plants such as Artocarpus altilis, Boesenbergia pandurata, Uvaria dac, Caesalpinia sappan, etc. [16][17][18][19]. In this chapter, we focus on A. altilis.…”

Section: Introductionmentioning

confidence: 99%

Prenylated Dihydrochalcones from Artocarpus altilis as Antiausterity Agents

Nguyen

Awale

2015

Mechanism of the Anticancer Effect of Phytochemicals

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“…A single flower at the end of twig reaches 6-12 cm diameter when blooming. Phytochemical investigation of U. grandiflora demonstrated the presence of several groups of natural chemical, including polyoxygenated cyclohexenes and aromatic derivatives, also showed interesting antitumour, antimalarial [1][2][3][4] , and antipancreatic cancer activities 5,6 . Polyoxygenated cyclohexenes have a rather simple molecular skeleton of 1-methylcyclohex-4-ene.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and anticancer activities of (−)-zeylenol from stems of Uvaria grandiflora

Seangphakdee¹,

Pompimon²,

Meepowpan³

et al. 2013

ScienceAsia

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Uvaria grandiflora has stimulated rigorous phytochemical investigation aimed at determining chemical structures and biological activities. In recent years, many polyoxygenated cyclohexenes have been isolated from this genus. This study reports that zeylenol isolated from the stems of U. grandiflora possess potential anti-inflammatory, anticancer, and caspase-3 activities. The structure of this compound was elucidated from spectroscopic analysis, particularly 2D NMR techniques. The anti-inflammatory effect and toxicity of zeylenol were evaluated in animal models and compared to that of reference drugs. In addition, the cytotoxicity of the isolated compound against human breast cancer MDA-MB231 and hepatocellular carcinoma HepG2 cell lines were studied. The test (−)-zeylenol at the dose of 1 mg/ear significantly inhibited oedema formation by 90%, 69%, 52%, and 52% after 15, 30, 60, and 120 min, respectively. Zeylenol was found to be toxic to both MDA-MB231 and HepG2 cells in a dose response manner with IC50 values of 54 ± 10 and > 80 µM, respectively. The compound induced MDA-MB231 cell apoptosis via caspase-3 activation. Zeylenol probably possesses anti-inflammatory activity by inhibiting the synthesis or release of various inflammatory mediators and might be used to induce human breast cancer MDA-MB231 cell apoptosis.

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Antiausterity Agents from Uvaria dac and Their Preferential Cytotoxic Activity against Human Pancreatic Cancer Cell Lines in a Nutrient-Deprived Condition

Cited by 43 publications

References 32 publications

Identification of plant extracts sensitizing breast cancer cells to TRAIL

Identification of plant extracts sensitizing breast cancer cells to TRAIL

Prenylated Dihydrochalcones from Artocarpus altilis as Antiausterity Agents

Anti-inflammatory and anticancer activities of (−)-zeylenol from stems of Uvaria grandiflora

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