Phenoxodiol – an isoflavone analog – induces apoptosis in chemoresistant ovarian cancer cells

Kamsteeg, Marijke; Rutherford, Thomas J.; Sapi, Eva; Hanczaruk, Bozena; Shahabi, Shoreh; Flick, Maryann B.; Brown, David; Mor, Gil

doi:10.1038/sj.onc.1206422

Cited by 175 publications

(182 citation statements)

References 41 publications

(35 reference statements)

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“…We found that SK-N-SH and SK-N-AS expressed high levels of XIAP. These findings correlated with previous studies showing that IAPs are highly expressed in many tumours and contribute to the resistance of cancers to apoptosis (Deveraux et al, 1998;Salvesen and Duckett, 2002;Kamsteeg et al, 2003). Treatment of the neuroblastoma cells with gold(III) porphyrin 1a inhibited the expression of XIAP.…”

Section: Discussionsupporting

confidence: 80%

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Xie

Sun

et al. 2009

Br J Cancer

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BACKGROUND: Gold(III) porphyrin 1a is a new class of anticancer drug, which inhibits cell proliferation of wide range of human cancer cell lines and induces apoptosis in human nasopharyngeal carcinoma cells. However, the underlying signalling mechanism by which gold(III) porphyrin 1a modifies the intracellular apoptosis pathways in tumour cells has not been explained in detail in neuroblastoma cells. METHODS: Cell proliferation and apoptosis were determined by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V binding, respectively. Western blot assay was used to detect proteins involved in apoptotic and Akt pathways. In vivo tumour growth was assessed by inoculating tumour cells to nude mice subcutaneously, and gold(III) porphyrin 1a was administrated intravenously. RESULTS: This study assessed the antitumour effect and mechanism of gold(III) porphyrin 1a on neuroblastoma in vitro and in vivo. Gold(III) porphyrin 1a displayed a growth inhibition and induction of apoptosis in neuroblastoma cells effectively in vitro, which was accompanied with release of cytochrome c and Smac/DIABLO and caspases activation. Further studies indicated that gold(III) porphyrin 1a inhibited X-linked inhibitor of apoptosis (XIAP). However, we found that gold(III) porphyrin 1a can induce a survival signal, Akt activation within minutes and could last for at least 24 h. To further confirm association between activation of Akt and the effectiveness of gold(III) porphyrin 1a, neuroblastoma cells were treated with API-2, an Akt-specific inhibitor. API-2 sensitised cells to gold(III) porphyrin 1a-induced apoptosis and growth inhibition. CONCLUSION: These results suggested that Akt may be considered as a molecular 'brake' that neuroblastoma cells rely on to slow down gold(III) porphyrin 1a-induced apoptosis and antiproliferation. Gold(III) porphyrin 1a is a mitochondrial apoptotic stimulus but also activates Akt, suggesting an involvement of Akt in mediating the effectiveness to growth inhibition and apoptosis by gold(III) porphyrin 1a and that inhibition of Akt can enhance the anticancer activity of gold(III) porphyrin 1a in neuroblastoma.

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Section: Discussionsupporting

confidence: 80%

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Xie

Sun

et al. 2009

Br J Cancer

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“…Protein extraction was done as previously described (Kamsteeg et al, 2003). Briefly, cell pellets were lysed on ice in 1 Â phosphate-buffered saline with 1% NP40, 0.1% SDS and freshly added 20 ml/ml protease inhibitor cocktail (Sigma Chemical, St Louis, MO, USA) and 2 mM phenylmethylsulfonyl fluoride (Sigma Chemical).…”

Section: Protein Preparationmentioning

confidence: 99%

“…A quantity of 20 mg of each protein sample was denatured in sample buffer and subjected to 12% SDS-polyacrylamide gel electrophoresis (PAGE) as previously described (Kamsteeg et al, 2003). The following antibodies were used: rabbit antihuman MyD88 (1:1,000), mouse anti-human IkBa (1:1,000), rabbit anti-human IKKa (1:1,000), rabbit anti-human IKKb (1:2,000) and rabbit anti-human b-actin (1:10,000).…”

Section: Sds-page and Western Blotsmentioning

confidence: 99%

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Regulation of IKKβ by miR-199a affects NF-κB activity in ovarian cancer cells

et al. 2008

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“…XIAP reagents have been identified and are in preclinical as well as clinical trial testing. 4,5,16,17 XIAP expression in non-small cell lung carcinoma has been reported in cell culture and animal models. [18][19][20][21] However, immunohistochemical studies specifically addressing XIAP expression in human lung adenocarcinoma and alveolar hyperplasias are lacking.…”

mentioning

confidence: 99%

Immunohistochemical detection of XIAP and p63 in adenomatous hyperplasia, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and well-differentiated adenocarcinoma

Orta

Gil

et al. 2008

Modern Pathology

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The critical distinction of bronchioloalveolar carcinoma (BAC), well-differentiated adenocarcinoma (WDAC) of lung, adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH), is based on morphological criteria alone, and is therefore potentially subjective. We examined expression of two markers, X-linked inhibitor of apoptosis protein (XIAP), the most potent of the inhibitor of apoptosis protein (IAP) family, and p63, a marker of bronchial reserve cells (BRC) and squamous cells, in these entities. H&E slides of 37 tissue blocks from 27 patients were reviewed and classified as AH (n ¼ 7), AAH (n ¼ 8), BAC (n ¼ 9) and WDAC (n ¼ 13). Immunostaining was performed on 4 lm sections with monoclonal anti-XIAP and monoclonal anti-p63. Granular or heterogeneous cytoplasmic staining for XIAP and nuclear staining for p63 were considered positive. Neither XIAP nor p63 were detected in normal lung alveolar cells. All seven AHs were negative for XIAP and negative or focally positive for p63. All eight AAHs were positive for XIAP and displayed p63 positivity in scattered cells. All BACs displayed XIAP positivity, which ranged from focal/weak to diffuse/strong. p63 was negative in seven and focally positive in two of nine BACs. Twelve of 13 WDACs showed XIAP positivity in a similar pattern to BAC; all were negative for p63. One aberrant case diagnosed on H & E as WDAC was negative for XIAP but strongly positive for p63. Significant XIAP expression appears to be useful for distinguishing AAH from AH. Commonality of XIAP staining in AAH, BAC and WDAC supports the possibility that AAH may be a premalignant lesion. The rarity of p63 expression confirms previous reports and supports a nonbronchial histogenesis of these entities. In contrast, diffuse p63 staining may facilitate the identification of rare cases that may have been misclassified as alveolar in origin based on morphology but may be of BRC origin.

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Phenoxodiol – an isoflavone analog – induces apoptosis in chemoresistant ovarian cancer cells

Cited by 175 publications

References 41 publications

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Regulation of IKKβ by miR-199a affects NF-κB activity in ovarian cancer cells

Immunohistochemical detection of XIAP and p63 in adenomatous hyperplasia, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and well-differentiated adenocarcinoma

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