Potential biochemical therapy of glioma cancer

Yin, Litian; Fu, Yuejun; Xu, Qinying; Yang, Jun; Liu, Zengli; Liang, Aihua; Fan, Xiaojun; Xu, Chao

doi:10.1016/j.bbrc.2007.07.167

Cited by 27 publications

(21 citation statements)

References 31 publications

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“…Increasing evidence suggests that resistance to apoptosis is a fundamental mechanism through which gliomas evade elimination in the face of conventional or targeted treatments (Ziegler et al, 2008). Recent studies have shown that inhibition of ion channels or pumps has provided a potential new approach for biochemical therapy of the brain tumors (Yin et al, 2007;Lefranc and Kiss, 2008) and inhibition of ion channels or pumps can increase the sensitivity of cancer cells to TRAIL (He et al, 2002;Kaddour-Djebbar et al, 2006;Monteith et al, 2007). Paxilline, an indole alkaloid from Penicillium paxilli, inhibits the activity of large-conductance Ca 2+ -activated K + channels (BK channels) (Sanchez and McManus, 1996) and the sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) (Bilmen et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Paxilline enhances TRAIL-mediated apoptosis of glioma cellsviamodulation of c-FLIP, survivin and DR5

Kang

Kim

et al. 2011

Exp Mol Med

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Abbreviations: FADD, fas-associated protein with death domain; TRAIL, tumor necrosis factor-related apoptosis-induced ligand AbstractTumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIP S ) and the caspase inhibitor, survivin, through proteasome-mediated degradation. Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. Thus, combined treatment regimens involving paxilline and TRAIL may offer an attractive strategy for safely treating resistant gliomas.

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Section: Introductionmentioning

confidence: 99%

Paxilline enhances TRAIL-mediated apoptosis of glioma cellsviamodulation of c-FLIP, survivin and DR5

Kang

Kim

et al. 2011

Exp Mol Med

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“…The observed effect of JAK2 and V617F JAK2 on the large conductance voltage-and Ca 2ϩ -activated K ϩ channels may be relevant for proliferation, migration, and metastasis of tumor cells (15,50,52,54,63,67). However, in some cells other K ϩ channels may functionally replace the BK channels and thus inhibition of BK channels does not necessarily interfere with those functions.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the large conductance voltage- and Ca²⁺-activated K⁺channels by Janus kinase 2

Hosseinzadeh

Almilaji

Honisch

et al. 2014

American Journal of Physiology-Cell Physiology

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The iberiotoxin-sensitive large conductance voltage- and Ca2+-activated potassium (BK) channels (maxi-K+-channels) hyperpolarize the cell membrane thus supporting Ca2+ entry through Ca2+-release activated Ca2+ channels. Janus kinase-2 (JAK2) has been identified as novel regulator of ion transport. To explore whether JAK2 participates in the regulation of BK channels, cRNA encoding Ca2+-insensitive BK channels (BKM513I+Δ899–903) was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, gain-of-function V617FJAK2, or inactive K882EJAK2. K+ conductance was determined by dual electrode voltage clamp and BK-channel protein abundance by confocal microscopy. In A204 alveolar rhabdomyosarcoma cells, iberiotoxin-sensitive K+ current was determined utilizing whole cell patch clamp. A204 cells were further transfected with JAK2 and BK-channel transcript, and protein abundance was quantified by RT-PCR and Western blotting, respectively. As a result, the K+ current in BKM513I+Δ899–903-expressing oocytes was significantly increased following coexpression of JAK2 or V617FJAK2 but not K882EJAK2. Coexpression of the BK channel with V617FJAK2 but not K882EJAK2 enhanced BK-channel protein abundance in the oocyte cell membrane. Exposure of BK-channel and V617FJAK2-expressing oocytes to the JAK2 inhibitor AG490 (40 μM) significantly decreased K+ current. Inhibition of channel insertion by brefeldin A (5 μM) decreased the K+ current to a similar extent in oocytes expressing the BK channel alone and in oocytes expressing the BK channel and V617FJAK2. The iberiotoxin (50 nM)-sensitive K+ current in rhabdomyosarcoma cells was significantly decreased by AG490 pretreatment (40 μM, 12 h). Moreover, overexpression of JAK2 in A204 cells significantly enhanced BK channel mRNA and protein abundance. In conclusion, JAK2 upregulates BK channels by increasing channel protein abundance in the cell membrane.

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“…Eventually, TMZ spontaneously undergoes hydrolysis to the active metabolite MTIC which rapidly breaks down to form the reactive methyl diazonium ion. The cytotoxicity of MTIC is due to the alkylation of DNA at the O6 and N7 positions of guanine [5,6], leading to the formation of O6-methylguanine in DNA, which mispairs with thymine during DNA replication triggering futile cycles of the mismatch repair system and subsequently leads to DNA damage [7,8]. Further, O6-methylguanine lesions induced by alkylating agents activate the p53-controlled DNA damage response pathway.…”

Section: Introductionmentioning

confidence: 99%

ENHANCED p53-DEPENDENT GROWTH INHIBITION OF HUMAN GLIOBLASTOMA CELLS BY COMBINATORIAL TREATMENT OF TEMOZOLOMIDE AND NOVEL PURIFIED NATURAL CARBOHYDRATE OF PLEUROTUS FLORIDA

Maji

Chatterjee

Basu

et al. 2017

Int J Pharm Pharm Sci

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Objective:This study was designed to analyze the combinatorial chemotherapeutic effect of temozolomide (TMZ), the most common drug in glioblastoma treatment and a purified carbohydrate (Fr-II) from the edible mushroom Pleurotus florida, on human glioblastoma cell lines.Methods: Fr-II was purified by size-exclusion chromatography and characterised by different mass spectroscopy analysis. Human glioblastoma cells were treated with TMZ, Fr-II, and combination of TMZ and Fr-II. Cell cytotoxicity was measured by MTT assay, cell cycle phase distribution was determined by cell cycle analysis and followed by the relative p53 protein expression was analyzed by western blot analysis.Results: Chemical analysis of Fr-II confirmed the glycosidically linked two units of glucose with terminally attached mannitol with mass of 506 Da. Fr-II treatment exhibited cytotoxicity in both the cell lines in a dose-dependent manner with most effective dose at 200µg/ml. When Fr-II (200µg/ml) was combined with a dose range of TMZ it showed a more cellular cytotoxicity compared to the cytotoxicity of TMZ alone with most oppressive combinatorial dose at 400µM (TMZ)+200µg/ml (Fr-II). In compliance, with the above results, both cell lines showed a 10% increase in no. of cells (p<0.05) in G2/M phase indicating an arrest of cell cycle and increased p53 protein expression (p<0.05) at the combinatorial dose than TMZ alone at 400µM, but Fr-II alone didn't show any cell cycle arrest nor did it show increased p53 expression. Conclusion:Therefore it confirms that Fr-II synergizes with TMZ to significantly intensify its anti-proliferative properties, thereby emerging as an effective element for combinatorial treatment of glioblastoma.

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Potential biochemical therapy of glioma cancer

Cited by 27 publications

References 31 publications

Paxilline enhances TRAIL-mediated apoptosis of glioma cellsviamodulation of c-FLIP, survivin and DR5

Paxilline enhances TRAIL-mediated apoptosis of glioma cellsviamodulation of c-FLIP, survivin and DR5

Upregulation of the large conductance voltage- and Ca²⁺-activated K⁺channels by Janus kinase 2

ENHANCED p53-DEPENDENT GROWTH INHIBITION OF HUMAN GLIOBLASTOMA CELLS BY COMBINATORIAL TREATMENT OF TEMOZOLOMIDE AND NOVEL PURIFIED NATURAL CARBOHYDRATE OF PLEUROTUS FLORIDA

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Potential biochemical therapy of glioma cancer

Cited by 27 publications

References 31 publications

Paxilline enhances TRAIL-mediated apoptosis of glioma cellsviamodulation of c-FLIP, survivin and DR5

Paxilline enhances TRAIL-mediated apoptosis of glioma cellsviamodulation of c-FLIP, survivin and DR5

Upregulation of the large conductance voltage- and Ca2+-activated K+channels by Janus kinase 2

ENHANCED p53-DEPENDENT GROWTH INHIBITION OF HUMAN GLIOBLASTOMA CELLS BY COMBINATORIAL TREATMENT OF TEMOZOLOMIDE AND NOVEL PURIFIED NATURAL CARBOHYDRATE OF PLEUROTUS FLORIDA

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Upregulation of the large conductance voltage- and Ca²⁺-activated K⁺channels by Janus kinase 2