Caspase‐3 is not essential for DNA fragmentation in MCF‐7 cells during apoptosis induced by the pyrrolo‐1,5‐benzoxazepine, PBOX‐6

Hyland, Edel M.; Campiani, Giuseppe; Ramunno, Anna; Nacci, Vito; Zisterer, Daniela M.

doi:10.1016/s0014-5793(02)02440-7

Cited by 93 publications

(61 citation statements)

References 14 publications

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“…They can be divided into two major subgroups, initiator (caspases-2, -8, -9, and -10), which activate the effector caspases (caspases-3, -6 and -7). Initiator caspases are activated by apoptotic signals, resulting in the activation of the effector caspases (Devarajan et al, 2002;Mc Geea et al, 2002). One of the major pathways for activation of caspase-9 (initiator caspase) involves calcium overload of mitochondria to trigger cytochrome c release , leading to the activation of caspase-9, and the subsequent activation of caspase-3.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

Fattahi

Ardekani²,

Zabihi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r 2 =0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC 50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

Fattahi

Ardekani²,

Zabihi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Depending on the cell model and the apoptotic agent used, it has been controversial in the past whether DNA fragmentation could occur in Casp3 Ϫ/Ϫ cells. These studies have been performed in hepatocytes and thymocytes (Zheng et al, 1998), P7 granule neurons (D'Mello et al, 2000), E16.0 and E19.0 neurons (Keramaris et al, 2000) from the mixed 129-B6 background, or the human MCF-7 cell line naturally lacking caspase-3 (Wolf et al, 1999;Mc Gee et al, 2002). Detection of DNA fragmentation in these various models was dependent on the apoptotic agent used, cell type, developmental stage, and sensitivity of the assay used.…”

Section: Discussionmentioning

confidence: 99%

Caspase-7 Expanded Function and Intrinsic Expression Level Underlies Strain-Specific Brain Phenotype ofCaspase-3-Null Mice

Houde¹,

Banks²,

Coulombe³

et al. 2004

J. Neurosci.

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Caspase-3-deficient mice of the 129S1/SvImJ (129) strain show severe brain development defects resulting in brain overgrowth and perinatal lethality, whereas on the C57BL/6J (B6) background, these mice develop normally. We therefore sought to identify the straindependent ameliorating gene. We biochemically isolated caspase-7 from B6-caspase-3-null (Casp3 Ϫ/Ϫ ) tissues as being the enzyme with caspase-3-like properties and capability of performing a caspase-3 surrogate function, apoptotic DNA fragmentation. Moreover, we show that, in contrast to the human enzymes, mouse caspase-7 is as efficient as caspase-3 at cleaving and thus inactivating ICAD (inhibitor of caspase-activated DNase), the inhibitor of apoptotic DNA fragmentation. Low levels of caspase-7 expression and activation correlate with lack of DNA fragmentation in 129-Casp3 Ϫ/Ϫ apoptotic precursor neurons, whereas B6-Casp3 Ϫ/Ϫ cells, which can fragment their DNA, show higher levels of caspase-7 expression and activation. The amount of caspase-7 activation in apoptotic precursor neurons is independent of the presence of caspase-3. Together, our findings demonstrate for the first time a strong correlation between caspase-7 activity, normal brain development, and apoptotic DNA fragmentation in Casp3 Ϫ/Ϫ mice.

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“…Our research group have established that some members of the pyrrolo-1,5-benzoxazepine (PBOX) family of compounds are capable of inducing apoptosis in cancerous cell lines derived from both haematological malignancies [promyelocytic leukaemia HL60 cells, Jurkat T-lymphoma cells, Hut-78 lymphoma cells, T cell leukaemia CEM cells and chronic myeloid leukaemia (CML) K562 cells] and solid tumours (breast carcinoma MCF-7 cells and ovarian A2780 cells) (5)(6)(7)(8)(9)(10). These results are supported by studies revealing impaired growth of tumours in a mouse 4T1 breast carcinoma tumour model (11), and a CML mouse model (12) and apoptosis in ex vivo CML and chronic lymphocytic leukaemia (CLL) patient samples (12,13).…”

Section: Introductionmentioning

confidence: 99%

Novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines, induce cell cycle arrest and apoptosis in prostate cancer cells

Nathwani

Cloonan²,

Stronach³

et al. 2010

Oncol Rep

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Abstract. Advanced hormone-refractory prostate cancer is associated with poor prognosis and limited treatment options. Members of the pyrrolo-1,5-benzoxazepine (PBOX) family of compounds exhibit anti-cancer properties in cancer cell lines (including multi-drug resistant cells), ex vivo patient samples and in vivo mouse tumour models with minimal toxicity to normal cells. Recently, they have also been found to possess anti-angiogenic properties in vitro. However, both the apoptotic pathways and the overall extent of the apoptotic response induced by PBOX compounds tend to be cell-type specific. Since the effect of the PBOX compounds on prostate cancer has not yet been elucidated, the purpose of this study was to investigate if PBOX compounds induce antiproliferative effects on hormone-refractory prostate cancer cells. We examined the effect of two representative PBOX compounds, PBOX-6 and PBOX-15, on the androgen-independent human prostate adenocarcinoma cell line, PC3. PBOX-6 and -15 displayed anti-proliferative effects on PC3 cells, mediated initially through a sustained G 2 /M arrest. G 2 /M arrest, illustrated as DNA tetraploidy, was accompanied by microtubule depolymerisation and phosphorylation of antiapoptotic proteins Bcl-2 and Bcl-x L and the mitotic spindle checkpoint protein BubR1. Phosphorylation of BubR1 is indicative of an active mitotic checkpoint and results in maintenance of cell cycle arrest. G 2 /M arrest was followed by apoptosis illustrated by DNA hypoploidy and PARP cleavage and was accompanied by degradation of BubR1, Bcl-2 and Bcl-x L . Furthermore, sequential treatment with the CDK1-inhibitor, flavopiridol, synergistically enhanced PBOXinduced apoptosis. In summary, this in vitro study indicates that PBOX compounds may be useful alone or in combination with other agents in the treatment of hormone-refractory prostate cancer. IntroductionProstate cancer is the leading cause of cancer and the second leading cause of cancer-related deaths among men in Europe and the USA (1). Early diagnosis following widespread PSA screening has resulted in most patients presenting with localized tumours. These patients generally exhibit good survival rates following radiotherapy or surgery. However, a number of patients still progress to or are diagnosed with locally advanced or metastatic tumours. While androgendeprivation therapy can slow the development of advanced metastatic prostate cancer, most tumours will still progress within a few years to an androgen-independent state (2). At this stage, treatment options become limited. The current treatment of choice for patients with advanced hormonerefractory prostate cancer is docetaxel-based chemotherapy. While these treatments significantly improve the overall survival of patients (3,4), the prognosis still remains poor for patients presenting with advanced stage prostate cancer. Therefore, the development of improved treatments and combinations are required.Our research group have established that some members of the pyrrolo-1,5-benzoxazepine (PBOX) famil...

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Caspase‐3 is not essential for DNA fragmentation in MCF‐7 cells during apoptosis induced by the pyrrolo‐1,5‐benzoxazepine, PBOX‐6

Cited by 93 publications

References 14 publications

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

Antioxidant and Apoptotic Effects of an Aqueous Extract of Urtica dioica on the MCF-7 Human Breast Cancer Cell Line

Caspase-7 Expanded Function and Intrinsic Expression Level Underlies Strain-Specific Brain Phenotype ofCaspase-3-Null Mice

Novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines, induce cell cycle arrest and apoptosis in prostate cancer cells

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