Negative growth control of osteosarcoma cell by Bowman–Birk protease inhibitor from soybean; involvement of connexin 43

Saito, Tetsuichiro; Sato, Hiromi; Virgona, Nantiga; Hagiwara, Hiromi; Kashiwagi, Kunihiro; Suzuki, Kazuyuki; Asano, Ryuji; Yano, Tomohiro

doi:10.1016/j.canlet.2007.01.021

Cited by 44 publications

(44 citation statements)

References 35 publications

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“…Similarly, we demonstrated that enforced Cx43 expression in H28 cells improves the effect of cisplatin against H28 cells (14). These reports strongly suggest that, in part, Cx-dependent tumor suppressive effects mitigate chemoresistance in several types of tumor cells.…”

Section: Discussionsupporting

confidence: 80%

“…In our previous study, enforced expression of Cx43 in MM cells exhibiting resistance to cisplatin significantly reduced this resistance (8), indicating that successful restoration of Cx43 by a treatment agent rather than Cx43 gene transfection may lead to the establishment of a novel effective MM therapy. Fortunately, in regards to the restoration of Cx43 expression in tumor cells, we and other research groups previously found that BBI effectively caused the induction of Cx43 in several types of tumor cells and that this induction is closely associated with negative growth control of tumor cells (14,17). Based on these reports, we speculated that BBI improves the efficacy of cisplatin in MM Figure 4.…”

Section: Discussionmentioning

confidence: 83%

“…Immunoblotting was performed as previously described (14). Briefly, the cell lysate was prepared in cell lysis/extraction reagent (Sigma), and 10 µg total protein extract from each sample was loaded onto 8% SDS-polyacrylamide gel.…”

Section: Immunoblot Analysismentioning

confidence: 99%

“…Although BBI has a broad spectrum of cancer-protective activities (10)(11)(12), knowledge of the exact mechanism(s) by which BBI exerts its anticarcinogenic effects remains limited. In our previous studies, we demonstrated that the induction of Cx43 by BBI contributes to the negative growth control of tumor cells in vivo as well as in vitro (13,14).…”

Section: Introductionmentioning

confidence: 98%

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Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Kashiwagi

Virgona

Yamada

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Malignant mesothelioma (MM) is an aggressive cancer with no effective treatment options. Enforced expression of the gap junction (GJ) component connexin 43 (Cx43) increases the sensitivity of MM cells to cisplatin. BowmanBirk protease inhibitor (BBI) induces the restoration of Cx43 in several types of tumor cells. In this study, we examined the capability of BBI to enhance the cytotoxic effect of cisplatin in MM cells via the induction of Cx43. Human MM H28 cells were used. Cell viability was evaluated by a WST-1 assay and proteasomal activity was determined by fluorometric analysis. Protein and mRNA levels were determined by immunoblot analysis and real-time RT-PCR, respectively. GJ function mediated by Cx43 was evaluated using the scrapeloading method. BBI effectively inhibited H28 cell growth in a dose-dependent manner (200-400 µg/ml). In parallel with the growth inhibition, Cx43 levels (mRNA and protein) and GJ function were elevated by BBI treatment. Knockdown of BBI-induced Cx43 by an antisense nucleotide treatment almost cancelled the growth inhibition. BBI enhanced cisplatin-induced cytotoxicity in H28 cells, and down-regulation of Cx43 by the antisense nucleotide treatment abrogated the enhancing effect of BBI. The induction of Cx43 by BBI contributed to Src inactivation and subsequent induction of Bax. Furthermore, an Src inhibitor (SU6656) also enhanced cisplatin-induced cytotoxicity in H28 cells. These results suggest that BBI improves the cytotoxic efficacy of cisplatin in H28 cells via the inhibition of Src signaling.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 83%

Section: Immunoblot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Kashiwagi

Virgona

Yamada

et al. 2011

Experimental and Therapeutic Medicine

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“…Thus, the effect of BBI on Cx43 may aid in the establishment of potential cancer chemoprevention and therapy based on Cx functions. BBI could therefore be a potential agent for cancer chemoprevention and therapy, as it stimulated the biosynthesis of Cx43 and suppressed the degradation of the Cx43 protein (29,30). Destruction of the Cx43 protein mainly depends on the ubiquitin-proteasome system (29,30), and chymotrypsinlike activity involved in the proteasome is specifically required for its degradation (30,31).…”

Section: Discussionmentioning

confidence: 99%

Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice

Sakurai

Suzuki²,

Nagaoka³

et al. 2008

Mol Med Rep

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Abstract. The present study was designed to confirm whether the Bowman-Birk inhibitor (BBI) induces an increase in p27 accumulation without S phase kinase-associated protein 2 (skp2) degradation by means of the expression of connexin (Cx) 43 as a gap junctional intercellular communication (GJIC)-dependent pathway in mice with M5076 ovarian sarcoma. M5076 ovarian sarcomas (1x10 5 cells/animal) were subcutaneously transplanted onto the backs of BDF 1 mice receiving 10, 20 or 40 mg/kg of purified BBI intraperitoneally. Relative tumor weight (p<0.01, r=0.503) was negatively correlated with the dose of BBI. In contrast, the relative density of Cx43 mRNA (p<0.01, r=0.570) and Cx43 (p<0.01, r=0.718) was positively correlated with the dose of BBI, as were p21 (p<0.01, r=0.633), p27 (p<0.01, r=0.561) and skp2 (p<0.01, r=0.733). We therefore suggest that the anticarcinogenic effects of BBI induce negative growth control by means of an increase in p27 accumulation caused by the expression of Cx43 as a GJIC pathway.

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Bioactivity of Proteins and Peptides from Peas (Pisum sativum, Vigna unguiculata, andCicer arietinumL)

Jiang

Wokadala

et al. 2010

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals

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Negative growth control of osteosarcoma cell by Bowman–Birk protease inhibitor from soybean; involvement of connexin 43

Cited by 44 publications

References 35 publications

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Connexin 43-dependent tumor-suppressing effect of the Bowman-Birk protease inhibitor on M5076 ovarian sarcoma-bearing mice

Bioactivity of Proteins and Peptides from Peas (Pisum sativum, Vigna unguiculata, andCicer arietinumL)

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