The purpose of this study was to evaluate the biochemical, morphometric, and histopathological changes associated with experimental periodontitis in rats in response to local administration of humic acid. Thirty-eight Wistar rats were divided into 5 experimental groups: nonligated (NL) group, ligature-only (LO) group, and ligature + local administration of humic acid (20, 80, and 150 mg/kg body weight per day for 15 days, respectively; L-20, L-80, and L-150 groups). Changes in alveolar bone levels were clinically measured as the distance from the cementoenamel junction to the alveolar bone crest with a stereomicroscope. Tissues were histopathologically examined to assess the osteoclast numbers, osteoblastic activity, and inflammatory cell infiltration among the study groups. Enzyme-linked immunosorbent assay interleukin1β (IL-1β) and IL-10 levels in serum and gingival homogenates were evaluated. At the end of 15 days, the alveolar bone loss was significantly higher in the LO group compared to the NL, L-20, and L-150 groups ( P < .05). The osteoclast number in the LO group was significantly higher than the NL, L-20, and L-150 groups ( P < .05). Inflammatory cell infiltration was significantly higher in the LO and L-80 groups than the other groups ( P < .05). The highest serum and gingival homogenate IL-10 levels were determined in the NL group ( P < .05). The serum and gingival homogenate IL-1β levels in LO group were significantly higher than the NL, L-20, and L-150 groups ( P < .05). Within the limits of this study, it can be suggested that humic acid, when administered locally at 20 and 80 mg/kg doses, may prevent alveolar bone loss in the rat model.

2019-04-01·Cancer Letters1区 · 医学

C-terminal HSP90 inhibitor L80 elicits anti-metastatic effects in triple-negative breast cancer via STAT3 inhibition

1区 · 医学

Article

作者: Farrand, Lee ; Sung, Daeil ; Seo, Jae Hong ; Jang, Seojin ; Kim, Ji Young ; Oh, Eunhye ; Cho, Tae-Min ; Kim, Yoon-Jae ; Hoang, Van-Hai ; Ann, Jihyae ; Lee, Jeewoo ; Nguyen, Cong-Truong

Triple-negative breast cancer (TNBC) is an aggressive heterogeneous disease with a divergent profile. It has an earlier tendency to form metastases and is associated with poor clinical outcomes due to the limited treatment options available. Heat-shock protein (HSP90) represents a potential treatment target as it promotes tumor progression and metastasis by modulating the maturation and stabilization of signal transduction proteins. We sought to investigate the efficacy of the C-terminal HSP90 inhibitor L80 on cell proliferation, breast cancer stem cell (BCSC)-like properties, tumor growth and metastasis. L80 suppressed cell viability and concomitantly inhibited AKT/MEK/ERK/JAK2/STAT3 signaling in TNBC cells but did not induce cytotoxicity in normal cells. L80 effectively targeted BCSC-like traits, together with significant reductions in the CD44high/CD24low-population, ALDH1 activity and mammosphere forming-ability. In support of the in vitro observations, L80 administration caused significant impairment in tumor growth, angiogenesis and distant metastases in an orthotopic allograft model with BCSC-enriched cells in vivo. These phenomena were associated with the suppression of BCSC-like characteristics and STAT3 dysfunction. Our findings highlight properties of the L80 compound that may be useful in suppressing metastatic TNBC.

2016-11-01·Bioorganic & Medicinal Chemistry3区 · 医学

Synthesis and biological evaluation of C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors

3区 · 医学

Article

作者: Kim, Ho Shin ; Park, So-Jung ; Park, Hyun-Ju ; Seo, Ji Hae ; Suh, Young-Ger ; Lee, Jeewoo ; Choi, Hoon ; Kim, Kyu-Won ; Ann, Jihyae ; Kim, Jun Yong ; Kim, Young-Myeong ; Lee, Su-Chan ; Lee, Ho-Young ; Kim, Joohwan ; Hong, Mannkyu ; Yoon, Suyoung ; Nguyen, Cong-Truong

Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80. It also inhibited in vitro hypoxia-mediated angiogenic processes in human retinal microvascular endothelial cells (HRMEC). The docking study of 5 showed a similar binding mode as L-80: it occupied the C-terminal ATP-binding pocket of HSP90, indicating that the anticancer and antiangiogenic activities of 5 were derived from HIF-1α destabilization by inhibiting the C-terminal ATP-binding site of hHSP90.

100 项与 L-80 相关的药物交易

登录后查看更多信息