Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

Yang, Zirong; Li, Meng; Peng, Xiulan; Lei, Xiaofei; Zhang, Jixiang; Dong, Weiguo

doi:10.1016/j.bbrc.2012.04.079

Cited by 39 publications

(39 citation statements)

References 25 publications

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“…This drug increased Bax protein expression and decreased Bcl-2 in MCF-7 and MDA-MB-231 breast cancer cell lines in comparison to their counterparts. Similar results were observed by other researchers and were related with Bax/Bcl-2 ratio (23,25). Bax/Bcl-2 ratio was evaluated from protein expression in MCF-10F cells treated with noscapine and increased ratio from 0.03 to 0.70 of Bax was found in relation to Bcl-2.…”

Section: Discussionsupporting

confidence: 89%

“…These results showed that cytotoxic effect of noscapine was mediated by apoptosis, being clearly observed on breast cancer cells. Previous research have shown that noscapine induced apoptosis in vitro in various types of cancer such as ovarian, neuroblastoma, colon, prostate and breast cancer among others (18,20,23,24).…”

Section: Discussionmentioning

confidence: 99%

“…The MCF-7 and MDA-MB-231 cells increased the ratio from 0.71 to 1.08 and from 0.99 to 3.64, respectively. The decrease in ratio Bax/Bcl-2 is characteristic of cancer (20,23,25). Noscapinetreated cells increased the expression of pro-apoptotic genes and decreased anti-apoptotic gene expression.…”

Section: Discussionmentioning

confidence: 99%

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Apoptotic effect of noscapine in breast cancer cell lines

Quisbert-Valenzuela

Calaf

2016

International Journal of Oncology

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Abstract. Cancer is a public health problem in the world and breast cancer is the most frequently cancer in women. Approximately 15% of the breast cancers are triple-negative. Apoptosis regulates normal growth, homeostasis, development, embryogenesis and appropriate strategy to treat cancer. Bax is a protein pro-apoptotic enhancer of apoptosis in contrast to Bcl-2 with antiapoptotic properties. Initiator caspase-9 and caspase-8 are features of intrinsic and extrinsic apoptosis pathway, respectively. NF-κB is a transcription factor known to be involved in the initiation and progression of breast cancer. Noscapine, an alkaloid derived from opium is used as antitussive and showed antitumor properties that induced apoptosis in cancer cell lines. The aim of the present study was to determine the apoptotic effect of noscapine in breast cancer cell lines compared to breast normal cell line. Three cell lines were used: i) a control breast cell line MCF-10F; ii) a luminallike adenocarcinoma triple-positive breast cell line MCF-7; iii) breast cancer triple-negative cell line MDA-MB-231. Our results showed that noscapine had lower toxicity in normal cells and was an effective anticancer agent that induced apoptosis in breast cancer cells because it increases Bax gene and protein expression in three cell lines, while decreases Bcl-xL gene expression, and Bcl-2 protein expression decreased in breast cancer cell lines. Therefore, Bax/Bcl-2 ratio increased in the three cell lines. This drug increased caspase-9 gene expression in breast cancer cell lines and caspase-8 gene expression increased in MCF-10F and MDA-MB-231. Furthermore, it increased cleavage of caspase-8, suggesting that noscapineinduced apoptosis is probably due to the involvement of extrinsic and intrinsic apoptosis pathways. Antiapoptotic gene and protein expression diminished and proapoptotic gene and protein expression increased noscapine-induced expression, probably due to decrease in NF-κB gene and protein expression and also by increase of IκBα gene expression induced by this drug. IntroductionCancer is a leading cause of death in both more and less economically developed countries; the burden is expected to grow worldwide due to the growth and aging of the population and improvements in early detection and treatment (1). Cancer is a major public health problem in many parts of the world. It is currently the second leading cause of death in the United States (1,2). Breast cancer, is the most frequently occurring cancer in women and some cases show slow growth with excellent prognosis, while aggressive tumors have poor prognosis (1-3). Breast tumors have also been identified into different subtypes based on the expression of estrogen receptors (ER), progesterone receptors (PR) and Her2 oncogene. The breast tumors that do not express ER, PR or Her2 are called triple-negative breast cancers and ~15% of the breast cancers fall into this category (3,4).Apoptosis is a process of programmed cell death that occurs in response to environmental stimuli and normal gro...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Apoptotic effect of noscapine in breast cancer cell lines

Quisbert-Valenzuela

Calaf

2016

International Journal of Oncology

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“…It causes cancer-related deaths every year (American Cancer Society, 2011). Surgical resection is the only curative treatment; therefore, developing novel agents with low toxicity and high efficacy is important (Yang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Comparison of phototoxic effects of hypericin-mediated photodynamictherapy in HT-29 and Caco-2 colon cancer cells

Süloğlu¹,

Selmanoğlu²,

Yılmaz³

et al. 2016

Turk J Biol

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Hypericin (HYP) is a plant-derived photosensitizer. HYP is preferentially taken up by tumor cells. We designed this study to compare HYP-mediated photodynamic therapy (PDT) in HT-29 and Caco-2 colon cell lines. Cells were treated with 0.04, 0.08, and 0.15 µM HYP concentrations and irradiated. The effect of HYP on metabolic profiles, alterations in lactate dehydrogenase (LDH) leakage, and cell cycle progression was investigated for the first time. Changes in glucose consumption, lactate production, and LDH leakage were analyzed. HYP-induced cell death was quantified by double staining (acridine orange/propidium iodide) and alterations in cell cycle regulation were analyzed with flow cytometry (using propidium iodide). LDH leakage and the number of dead cells were elevated, and glucose consumption and lactate production decreased in a dose-and time-dependent manner. PDT resulted in an induction of apoptosis, mostly at the 0.08 µM HYP concentration. Apoptosis and/or necrosis were increased in the 0.15 µM HYP group. The accumulation of cells in the G2/M phase might account for the growth inhibition in HT-29 and Caco-2 cells with 0.08 µM HYP photoactivation. The observed G2/M arrest suggested that HYP may slow down the growth of colon cancer cells by regulating the cell cycle, leading either to growth inhibition or to initiation of apoptotic pathways.

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“…It is the third most common malignant disease among men and the second among women (Ku et al 2012). While surgical resection is the only known curative treatment, a significant number of patients still develop local recurrence and/or distant metastasis (Yang et al 2012). Therefore, identification of factors that accurately predict the prognosis is essential.…”

Section: Introductionmentioning

confidence: 99%

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

2014

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Dysadherin is a recently found anti-adhesion molecule, therefore detection and down regulation of its expression is promising in cancer treatment. The up-regulation of dysadherin contributes to colon cancer recurrence and metastasis. Dysadherin also has connections with cytoskeletal proteins and it can cause alterations in the organisation of filamentous actin (Factin) in metastatic cancers. In this study, hypericin (HYP)-mediated photodynamic therapy (PDT) was performed in two different grade colon adenocarcinoma cell lines HT-29 (Grade I) and Caco-2 (Grade II). Cells were treated with 0.04, 0.08 or 0.15 lM HYP concentrations and irradiated with (4 J/cm 2 ) fluorescent lamps. The effects of HYP was examined 16 and 24 h after the activation. We investigated for the first time the effect of HYP-mediated PDT on the expression of dysadherin and F-actin organisation. According to the results, HYP mediated PDT caused a decrease in gene expression and immunofluorescence staining of dysadherin and an increase in actin stress fibers and actin aggregates in HT-29 and Caco-2 cell lines. Besides, cytotoxicity, number of floating cells and apoptotic index changed depending on the cell type, HYP concentration and incubation time. We have demonstrated for the first time that dysadherin and F-actin could be target molecules for HYP-

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Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

Cited by 39 publications

References 25 publications

Apoptotic effect of noscapine in breast cancer cell lines

Apoptotic effect of noscapine in breast cancer cell lines

Comparison of phototoxic effects of hypericin-mediated photodynamictherapy in HT-29 and Caco-2 colon cancer cells

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

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