Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

Matsui, Yoshiyuki; Ueda, Shugo; Watanabe, Jun; Kuwabara, Ichiro; Ogawa, Osamu; Nishiyama, Hiroyuki

doi:10.1158/0008-5472.can-06-3283

Cited by 45 publications

(45 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FACS analysis was performed as described in Materials and methods. regulation of p53 phosphorylation in J82 cells, suggesting p53 is mutated in this cell line, as described by Matsui et al (30). On the other hand, Ser15, Ser20 and Ser46 were phosphorylated in RT112 cells upon treatment with GTC and/or GTC/lapatinip (Fig 7), which was shown to contain wild-type p53 (30).…”

Section: Lapatinib and Combination Chemotherapy Affect The Cell Cyclesupporting

confidence: 70%

Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells

et al. 2009

View full text Add to dashboard Cite

Abstract. Survival rate of patients diagnosed with the invasive form of bladder cancer is low suggesting an urgent need to implement novel treatments. GTC (gemcitabine, paclitaxel and cisplatin) is a new chemotherapeutic regimen, which has shown promise in clinical trials. Given that receptor tyrosine kinases of the ErbB family are overexpressed in a high proportion of metastatic bladder tumours, approaches involving small-molecule inhibitors of ErbB receptors in combination with conventional cytostatic drugs are of potential interest. Here, we show that the dual inhibitor of ErbB receptors, lapatinib, enhances cytostatic and induces cytotoxic effects of GTC in two bladder cancer cell lines which differ with regard to expression levels of proteins taking part in the ErbB pathway. Lapatinib inhibited phosphorylation of ErbB receptors and also reduced the level of phosphorylated AKT. Flow cytometry analysis demonstrated that GTC treatment affects cell cycle distribution differently in the presence or absence of lapatinib. In RT112 cells, which express high levels of ErbB receptors and harbour wild-type p53, combined GTC/lapatinib treatment resulted in the phosphorylation of p53 at Ser46 and accumulation of sub-G 1 cell populations. Our data indicate that a combinatorial approach involving GTC and lapatinib may have therapeutic potential in a subset of bladder tumours depending on the genetic context. IntroductionBladder cancer is a worldwide disease with poor clinical outcome, especially among patients with the muscle invasive form of the disease (1). Several combinations of chemotherapeutic agents are used in treatment of metastatic transitional cell carcinoma (TCC) of the bladder. The combination of methotrexate, vinblastine, doxorubicin and cisplatin was previously considered the 'gold standard' chemotherapy treatment of TCC, although the median survival was only one year (2). Administration of the gemcitabine and cisplatin regimen has resulted in decreased toxicity, but has not improved survival rates (3). At present, a combination of gemcitabine, paclitaxel (taxol) and cisplatin (GTC) with median survival of 22 months is considered as a promising approach (4). In view of the continuing modest survival rates, novel targeted therapies for the treatment of advanced TCC of the bladder are urgently required. Much interest currently centres on modifying the activity of epidermal growth factor receptor (EGFR) family members (5-7). This family, which has been implicated in human cancers, comprises four receptors, ErbB-1 (HER1, EGFR), ErbB-2 (HER2), ErbB-3 (HER3) and ErbB-4 (HER4) (8). High expression of ErbB-1/ErbB-2, which has been described in TCC of the bladder, is an independent predictor of reduced survival (9-12). In contrast, high expression of ErbB-3/ErbB-4 is associated with favourable clinical outcome in TCC patients (13,14).The ErbB receptors are composed of an extracellular ligand-binding region, transmembrane domain, and a cytoplasmic region containing a tyrosine kinase domain and autophosphorylation sit...

show abstract

Section: Lapatinib and Combination Chemotherapy Affect The Cell Cyclesupporting

confidence: 70%

Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells

et al. 2009

View full text Add to dashboard Cite

show abstract

“…RNA isolation, RT-PCR and Real-time quantitative RT-PCR Total RNA preparation and first-strand cDNA synthesis was performed as described previously (Matsui et al, 2007). Primer sequences used for cDNA amplification were as follows: p21 sense 5 0 -ATTAGCAGCGGAACAAGGAGTCAGACAT-3 0 and antisense 5 0 -CTGTGAAAGACAGAACAGTACAG GGT-3 0 ; MDM2 sense 5 0 -AATCATCGGACTCAGGTAC A-3 0 and antisense 5 0 -GTCAGCTAAGGAAATTTCAGG-3 0 ; PUMA sense 5 0 -CCAAACGTGACCACTAGCCT-3 0 and antisense 5 0 -ACAGGATTCACAGTCTGGGC-3 0 .…”

Section: Cell Culturementioning

confidence: 99%

“…After drug treatments, cells were collected and lysed as described previously (Matsui et al, 2007). Thirty to 50 micrograms of protein samples were separated by SDS-PAGE and transferred onto a polyvinylidene difluoride membrane following standard methods.…”

Section: Immunoblotting and Immunoprecipitationmentioning

confidence: 99%

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

View full text Add to dashboard Cite

To improve conventional chemotherapeutic efficacy, a combination use of traditional medicines is effective but detailed mechanisms have been rarely elucidated. In the this study, we attempted to clarify how triptolide (PG490), an oxygenated diterpene derived from a Chinese herb, enhances the cisplatin (CDDP)-induced cytotoxicity in urothelial cancer cells. Our results showed that a combined CDDP/triptolide therapy induced apoptosis in urothelial cancer cell lines with wild-type p53, but not in those with mutant-type p53 or normal human urothelium. As the mechanism, triptolide suppressed CDDP-induced p53 transcriptional activity, leading to p21 attenuation, which promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and Bax. We further demonstrated that the functional regulation of p53 by triptolide was mediated by an intranuclear association of p53 with glycogen synthase kinase-3b (GSK3b), which was inactivated by protein kinase C (PKC). This modulation of the PKC-GSK3b axis by triptolide was observed in a cancer-specific manner. A mouse xenograft model also showed that a combined CDDP/triptolide therapy completely suppressed tumor growth without any side effects. We expect that cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide may effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer.

show abstract

“…Galectin-7 expression varied in different types of bladder cancers. Elevated expression of galectin-7 had been observed in highly differentiated squamous cell carcinoma, while urothelial carcinoma showed reduced galectin-7 expression as compared to respective normal cells (Ostergaard et al, 1997;Matsui et al, 2007). Elevated expression of galectin-7 had been observed in more differentiated tumours as compared to less differentiated tumour (Ostergaard et al, 1997).…”

Section: Bladder Cancermentioning

confidence: 99%

“…In addition to this, accumulation of intracellular reactive oxygen species (ROS) and activation of JNK and Bax had been observed in galectin-7 transfected cells than control transfectants. Based on these findings it was proposed that galectin-7 might act as predictive marker of chemo-sensitivity against CDDP (Matsui et al, 2007).…”

Section: Bladder Cancermentioning

confidence: 99%

Roles of Galectin-7 in Cancer

Kaur

Kaur²,

Kamboj³

et al. 2016

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Galectins are β-galactoside binding lectins that contain one or more carbohydrate recognition domains. As a consequence of sugar-binding properties, galectins exhibit a variety of interactions with glycoproteins, thus playing important roles in various pathological processes. A number of studies have shown roles of galectins in cancer. Galectin-7 is a prototype member of the galectin family implicated in epithelial stratification and cell migration. It can act as a potent dual regulator in different types of cancer. Galectin-7 may contribute either to neoplastic transformation and tumour progression through regulation of cell growth, cell cycle, angiogenesis, apoptosis and cell migration or may have a protective effect in cancer depending on the tissue type. A perusal of the literature indicates particular roles of galectin-7 in carcinomas and melanomas, while contributions await greater exploration in other types of cancers including sarcomas and leukemia. This review collectively summarizes available literature on expression and roles of galectin-7 in different cancers.

show abstract

Sensitizing Effect of Galectin-7 in Urothelial Cancer to Cisplatin through the Accumulation of Intracellular Reactive Oxygen Species

Cited by 45 publications

References 47 publications

Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells

Lapatinib, a dual inhibitor of ErbB-1/-2 receptors, enhances effects of combination chemotherapy in bladder cancer cells

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Roles of Galectin-7 in Cancer

Contact Info

Product

Resources

About