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Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment.

Jakubowicz-Gil J, Langner E, Bądziul D, Wertel I, Rzeski W - Tumour Biol. (2013)

Bottom Line: Our results clearly indicate that quercetin and temozolomide induce apoptosis very significantly, having no effect on autophagy induction.At the molecular level, it was correlated with caspase 3 and 9 activation, cytochrome c release from the mitochondrium and a decrease in the mitochondrial membrane potential.Additionally, it was accompanied by changes in the nuclear morphology from circular to 'croissant like'.

View Article: PubMed Central - PubMed

Affiliation: Department of Comparative Anatomy and Anthropology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland. jjgil@poczta.umcs.lublin.pl

ABSTRACT
Glioblastoma multiforme is the most aggressive primary brain tumour. At the cellular and molecular levels, several mechanisms responsible for apoptosis or autophagy induction are blocked. Identification of molecular targets stimulating cells to initiate programmed cell death should be performed for therapeutic purposes. A promising solution is the combination of temozolomide and quercetin. The aim of our study was to evaluate the effect of both drugs, applied alone and in combinations, on apoptosis and autophagy induction in human glioblastoma multiforme T98G cells. Our results clearly indicate that quercetin and temozolomide induce apoptosis very significantly, having no effect on autophagy induction. At the molecular level, it was correlated with caspase 3 and 9 activation, cytochrome c release from the mitochondrium and a decrease in the mitochondrial membrane potential. Both drugs are also potent Hsp27 and Hsp72 inhibitors. This suggests that the apoptotic signal goes through an internal pathway. Increased expression of caspase 12 and the presence of several granules in the cytoplasm after temozolomide treatment with or without quercetin preceding appearance of apoptosis may suggest that apoptosis is initiated by ER stress. Additionally, it was accompanied by changes in the nuclear morphology from circular to 'croissant like'.

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The mitochondrial membrane potential in T98G cells stained with DiOC6(3), incubated separately with 50 μM of quercetin (Q) and 50 μM of temozolomide (T) or in combination of both drugs for 48 h and analysed by flow cytometry. C control cells, QT cells pre-incubated with quercetin, Q + T simultaneous drug treatment, TQ pre-incubation with temozolomide. *P < 0.05
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Fig4: The mitochondrial membrane potential in T98G cells stained with DiOC6(3), incubated separately with 50 μM of quercetin (Q) and 50 μM of temozolomide (T) or in combination of both drugs for 48 h and analysed by flow cytometry. C control cells, QT cells pre-incubated with quercetin, Q + T simultaneous drug treatment, TQ pre-incubation with temozolomide. *P < 0.05

Mentions: It is known that a decreased mitochondrial membrane potential is a good indicator of apoptotic cell death [4]. In our experiments, both quercetin and temozolomide applied alone or in combination decreased this potential (Fig. 4). The lowest value was observed after treatment with the simultaneous application of quercetin and temozolomide.Fig. 4


Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment.

Jakubowicz-Gil J, Langner E, Bądziul D, Wertel I, Rzeski W - Tumour Biol. (2013)

The mitochondrial membrane potential in T98G cells stained with DiOC6(3), incubated separately with 50 μM of quercetin (Q) and 50 μM of temozolomide (T) or in combination of both drugs for 48 h and analysed by flow cytometry. C control cells, QT cells pre-incubated with quercetin, Q + T simultaneous drug treatment, TQ pre-incubation with temozolomide. *P < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713258&req=5

Fig4: The mitochondrial membrane potential in T98G cells stained with DiOC6(3), incubated separately with 50 μM of quercetin (Q) and 50 μM of temozolomide (T) or in combination of both drugs for 48 h and analysed by flow cytometry. C control cells, QT cells pre-incubated with quercetin, Q + T simultaneous drug treatment, TQ pre-incubation with temozolomide. *P < 0.05
Mentions: It is known that a decreased mitochondrial membrane potential is a good indicator of apoptotic cell death [4]. In our experiments, both quercetin and temozolomide applied alone or in combination decreased this potential (Fig. 4). The lowest value was observed after treatment with the simultaneous application of quercetin and temozolomide.Fig. 4

Bottom Line: Our results clearly indicate that quercetin and temozolomide induce apoptosis very significantly, having no effect on autophagy induction.At the molecular level, it was correlated with caspase 3 and 9 activation, cytochrome c release from the mitochondrium and a decrease in the mitochondrial membrane potential.Additionally, it was accompanied by changes in the nuclear morphology from circular to 'croissant like'.

View Article: PubMed Central - PubMed

Affiliation: Department of Comparative Anatomy and Anthropology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland. jjgil@poczta.umcs.lublin.pl

ABSTRACT
Glioblastoma multiforme is the most aggressive primary brain tumour. At the cellular and molecular levels, several mechanisms responsible for apoptosis or autophagy induction are blocked. Identification of molecular targets stimulating cells to initiate programmed cell death should be performed for therapeutic purposes. A promising solution is the combination of temozolomide and quercetin. The aim of our study was to evaluate the effect of both drugs, applied alone and in combinations, on apoptosis and autophagy induction in human glioblastoma multiforme T98G cells. Our results clearly indicate that quercetin and temozolomide induce apoptosis very significantly, having no effect on autophagy induction. At the molecular level, it was correlated with caspase 3 and 9 activation, cytochrome c release from the mitochondrium and a decrease in the mitochondrial membrane potential. Both drugs are also potent Hsp27 and Hsp72 inhibitors. This suggests that the apoptotic signal goes through an internal pathway. Increased expression of caspase 12 and the presence of several granules in the cytoplasm after temozolomide treatment with or without quercetin preceding appearance of apoptosis may suggest that apoptosis is initiated by ER stress. Additionally, it was accompanied by changes in the nuclear morphology from circular to 'croissant like'.

Show MeSH
Related in: MedlinePlus