Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.

Činátl, Jindřich; Kotchetkov, Rouslan; Vogel, Jens‐Uwe; Woodcock, Barry G.; Matoušek, Jaroslav; Poučková, P; Kornhuber, B.

doi:10.3892/ijo.15.5.1001

Cited by 29 publications

(34 citation statements)

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“…SK-N-SH cell line possesses multidrug resistance (MDR) phenotype and SK-N-AS cell line is non-MDR phenotype. (Cinatl et al, 1999) Mice were administered gold(III) porphyrin 1a (10.0 mg kg À1 ) every 3 days intravenously till day 21 postinoculation. Control group received vehicle alone.…”

Section: Effects Of Gold(iii) Porphyrin 1a On Tumour Growth In Vivomentioning

confidence: 99%

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: Effects Of Gold(iii) Porphyrin 1a On Tumour Growth In Vivomentioning

confidence: 99%

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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“…[1][2][3][4][5] The antitumor activity was shown for BS-RNase from bovine seminal, [6][7][8][9] onconase from oocytes of Rana pipiens, [10][11][12] bovine pancreatic RNase A, 13 cSBL and jSBL RNases from Rana catesbeiana and Rana japonica, 14 microbial RNases [15][16][17] and conjugates of RNases with various molecules. [18][19][20] One of the properties that are important for potential therapeutic application of RNases is their ability to induce cancer cell death by apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells

et al. 2013

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“…LP117 also sensitized a range of further ABCB1-expressing cell lines to vincristine, including two other neuroblastoma cell lines with acquired resistance to vincristine (IMR-32 r VCR 10 , UKF-NB-2 r VCR 10 ), UKF-NB-3 sub-lines adapted to doxorubicin (UKF-NB-3 r DOX 20 ) or paclitaxel (UKF-NB-3 r PCL 10 ), and the intrinsically ABCB1-expressing neuroblastoma cell line UKF-NB-4 [20,22,24] but did not sensitize UKF-NB-3 r DOX 20 or UKF-NB-3 r VCR 10 cells to the non-ABCB1 substrate cisplatin. These data, together with the finding that LP117 stimulates ABCB1 ATPase activity, suggest that LP117 and other pirinixic derivatives interfere with ABCB1 function, possibly being substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Table 3). LP117 (2μM) also sensitized the vincristine-resistant ABCB1-expressing neuroblastoma cell lines IMR-32 r VCR 10 and UKF-NB-2 r VCR 10 , the ABCB1-expressing neuroblastoma cell line UKF-NB-4 that was isolated as multi-drug resistant cell line from a patient [19,20,22], the ABCB1-expressing doxorubicin-resistant UKF-NB-3 sub-line UKF-NB-3 r DOX 20 , and the ABCB1-expressing paclitaxel-resistant UKF-NB-3 sub-line UKF-NB-3 r PCL 10 to vincristine ( Figure 3B, Suppl. Table 4).…”

Section: Effects Of Selected Pirinixic Acid Derivatives On the Viabilmentioning

confidence: 99%

Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport

Michaelis¹,

Rothweiler²,

Wurglics³

et al. 2016

European Journal of Cancer

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Pirinixic acid derivatives, a new class of drug candidates for a range of diseases, interfere with targets including PPARa, PPARg, 5-lipoxygenase (5-LO), and microsomal prostaglandin and E2 synthase-1 (mPGES1). Since 5-LO, mPGES1, PPARa, and PPARg represent potential anti-cancer drug targets, we here investigated the effects of 39 pirinixic acid derivatives on prostate cancer (PC-3) and neuroblastoma (UKF-NB-3) cell viability and, subsequently, the effects of selected compounds on drug-resistant neuroblastoma cells. Few compounds affected cancer cell viability in low micromolar concentrations but there was no correlation between the anti-cancer effects and the effects on 5-LO, mPGES1, PPARa, or PPARg. Most strikingly, pirinixic acid derivatives interfered with drug transport by the ATP-binding cassette (ABC) transporter ABCB1 in a drug-specific fashion. LP117, the compound that exerted the strongest effect on ABCB1, interfered in the investigated concentrations of up to 2μM with the ABCB1-mediated transport of vincristine, vinorelbine, actinomycin D, paclitaxel, and calcein-AM but not of doxorubicin, rhodamine 123, or JC-1. In silico docking studies identified differences in the interaction profiles of the investigated ABCB1 substrates with the known ABCB1 binding sites that may explain the substrate-specific effects of LP117. Thus, pirinixic acid derivatives may offer potential as drug-specific modulators of ABCB1-mediated drug transport.

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Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis.

Cited by 29 publications

References 0 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

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells

Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport

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