Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer

Chougule, Mahavir B.; Patel, Apurva R.; Jackson, Tanise; Singh, Mandip

doi:10.1371/journal.pone.0017733

Cited by 92 publications

(94 citation statements)

References 42 publications

(80 reference statements)

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“…It was also demonstrated that triple-negative cells MDA-MB-231 was more sensitive than triple-positive MCF-7 cells in treatment with noscapine which agrees with the results of other studies (21,22). Noscapine provides promise as an effective anticancer agent with lower toxicity on normal cells.…”

Section: Discussionsupporting

confidence: 88%

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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: 88%

“…Furthermore, previous studies have shown high levels of NF-κB polypeptides (both p100 and p52) in mammary carcinoma cell lines and primary tumors compared to normal breast cells (17,33,34). These results with noscapine in breast cancer cell lines are the first to be published; however, studies have been reported in other cancers (22,32).…”

Section: Discussionmentioning

confidence: 73%

Apoptotic effect of noscapine in breast cancer cell lines

Quisbert-Valenzuela

Calaf

2016

International Journal of Oncology

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“…The triple negative breast cancer (TNBC) cells MDA-MB-468 and MDA-MB-231 are null for wild type ER, PR or her2/neu activity [47]. Figs.…”

Section: Ni-07 Demonstrates Similar Results In Killing Effectiveness mentioning

confidence: 99%

The Natural Product NI-07, Is Effective Against Breast Cancer Cells While Showing No Cytotoxicity to Normal Cells

Gollahon¹

2011

TOBCANJ

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Abstract:With the exception of a few anticancer agents, most breast cancer chemotherapeutics currently used have devastating effects on normal cells. We investigated the effectiveness of the natural product NI-07, derived from Arctium lappa, to determine its killing potential on breast cancer cells and its cytotoxic effects in breast normal cells. The breast cancer cell lines HCC1419, MCF7, MDA-MB-231, MDA-MB-468, SKBR3, the normal mammary epithelial cell line HME 50 HT and the normal mammary fibroblast cell line CCD-1074sk were analyzed in concurrently treated cultures of NI-07, Taxol™ or Untreated. NI-07-treated and Taxol™ -treated cells were cultured for two weeks to assess cell resistance/recovery. Cell viability was determined by cell counts, Trypan Blue exclusion and microscopy. Additionally, cell viability and cytotoxicity were measured by XTT. Statistical significance (p 0.05) of NI-07 to Untreated or Taxol™ was first determined using Two-Way ANOVA. Identified significant differences were further analyzed by One-Way ANOVA and Tukey's test for honestly significant differences. The effect size of NI-07 compared to untreated or Taxol™ was determined using Cohen's d. Our results showed significant declines in cell viability occurring in NI-07-treated cancer cells after 48 hours of treatment in contrast to the more rapid effect of Taxol™ (<24h). Additionally, cancer cell recovery was less effective in NI-07 versus Taxol™. Furthermore, NI-07 showed no cytotoxicity in normal cells. This lack of cytotoxicity, coupled with its killing efficiency in cancer cells, suggests that NI-07 could potentially make a strong anti-cancer compound or neo-adjuvant to current chemotherapy-based treatments.

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“…The highest NF-κB activity in MDA-MB-231 cells was associated with the highest expression of VEGF mRNA, while the activity and the mRNA levels were moderate in MCF cells and the lowest in T47D cells (Shibata et al, 2002). A similar study showed that the triple negative breast cancers (MDA-MB231 and MDA-MB-468) or MCF-7 and T47D implanted mice expressed higher VEGF and NF-κB activation in their tumor tissues (Chougule et al, 2011;Antoon et al, 2011). Recently, Ambs and Glynn revived that inducible nitric oxide synthase (iNOS) has been observed in many types of human tumors.…”

mentioning

confidence: 72%