Hiroaki Suga

Publications (3)8.37 Total impact

• Article: Novel acridine-based N-acyl-homoserine lactone analogs induce endoreduplication in the human oral squamous carcinoma cell line SAS.

  Hongbo Chai, Masaharu Hazawa, Yoichiro Hosokawa, Jun Igarashi, Hiroaki Suga, Ikuo Kashiwakura
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  ABSTRACT: The cytotoxicity of novel acridine-based N-acyl-homoserine lactone (AHL) analogs was investigated on the human oral squamous carcinoma cell line SAS. One analog induced G2/M phase arrest at 5.3-10.6 µM and induced polyploidy at a higher dose (21.2 µM). Importantly, treatment of SAS cells with a combination of the AHL analog and the Jun N-terminal kinase (JNK) inhibitor, SP600125, prevented mitosis and induced polyploidy. The AHL analog synergized with X-irradiation to inhibit clonogenic survival of SAS cells; however, its radiosensitizing effects were relative to not X-irradiation-induced apoptosis but mitotic failure following enhanced expression of Aurora A and B. These results suggest that the active AHL analog showed growth-suppressive and radiosensitizing effects, which involve polyploidy followed by G2/M accumulation and atypical cell death in the SAS cell line.
  Biological & Pharmaceutical Bulletin 01/2012; 35(8):1257-63. · 1.66 Impact Factor
• Article: Caspase-independent apoptosis induction of quorum-sensing autoinducer analogs against chronic myeloid leukemia K562.

  Masaharu Hazawa, Michiko Kudo, Toshihiro Iwata, Kazuki Saito, Kenji Takahashi, Jun Igarashi, Hiroaki Suga, Ikuo Kashiwakura
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  ABSTRACT: Quorum sensing is defined as the ability of microorganisms to sense their population density via the release of signaling molecules called autoinducers (AIs). Various types of AI analogs were prepared and their antitumor properties against chronic myeloid leukemia (CML) K562 cells were investigated. Two AI analogs induced progressive apoptosis with JNK activation and p21 induction. In addition, this induction of apoptosis is not related to bcr-abl kinase, which sustains CML proliferation. However, the progression of apoptosis was not inhibited by a caspase family inhibitor. These results suggested that AI analogs could induce caspase-independent apoptosis in CML K562.
  Investigational New Drugs 01/2011; 30(3):862-9. · 3.36 Impact Factor
• Article: Functional properties of synthetic N-acyl-L-homoserine lactone analogs of quorum-sensing gram-negative bacteria on the growth of human oral squamous carcinoma cells.

  Hongbo Chai, Masaharu Hazawa, Naoko Shirai, Jun Igarashi, Kenji Takahashi, Yoichiro Hosokawa, Hiroaki Suga, Ikuo Kashiwakura
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  ABSTRACT: Quorum sensing is defined as the ability of microorganisms to sense their population density via the release of signaling molecules composed of acyl-homoserine lactone (AHL), which is a type of autoinducer (AI). Previous structure-activity relationship (SAR) studies demonstrated that the 3-oxo group, homoserine lactone of L-form, and long acyl side chain have crucial roles in apoptosis induction. Various types of synthetic AI analogs of Pseudomonas aeruginosa were prepared, and SAR study was conducted to determine their effects against human oral squamous carcinoma cells derived from gingival carcinoma Ca9-22 cells and tongue cancer SAS cells. Not only the antiproliferative potential but also the radiation-sensitizing effects against these cells were examined. It was found that antiproliferative activity partly depended on HSL structure and acyl side chain length. Moreover, a few compounds, compound 5 and 87, showed antiproliferative effects against both Ca9-22 and SAS cells, and also induced radiation-sensitizing effects against Ca9-22 cells. Compound 5 alone induced apoptotic cell death accompanied by sub-G1 phase accumulation in cell cycle and caspase-3 activation, and radiation-sensitizing effects of compound 5 could be attributed to enhanced apoptosis induction. In contrast, there were no remarkable alterations in cell cycle distribution in Ca9-22 treated with compound 87 alone or in combination. However, both compounds lack 3-oxo and their acyl side chain lengths are not necessarily long. This SAR study demonstrated that HSL analogs, which lacked the recommended characteristics for apoptosis induction clearly showed antiproliferative and radiation-sensitizing activity in Ca9-22 cells.
  Investigational New Drugs 09/2010; 30(1):157-63. · 3.36 Impact Factor