Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells

Gonda, Kazue; Tsuchiya, Hiroyuki; Sakabe, Tomohiko; Akechi, Yuji; Ikeda, Remina; Nishio, Ren; Terabayashi, Kei; Ishii, Kyoko; Matsumi, Yoshiaki; Ashla, An Afida; Okamoto, Hideharu; Takubo, Kazuko; Matsuoka, Satomi; Watanabe, Yumi; Hoshikawa, Yasushi; Kurimasa, Akihiro; Shiota, Goshi

doi:10.1016/j.bbrc.2008.04.008

Cited by 56 publications

(22 citation statements)

References 25 publications

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“…Apoptosis may represent an important mechanism by which retinoids can inhibit tumour cell growth [74][75][76]. We found that the ATRA growth inhibitory effect on LM38-LP cells was associated with a lower expression of phosphorylated Erk (pErk) and phosphorylated Akt (pAkt), suggesting the inactivation of two main regulatory pathways related to cellular proliferation and survival [13].…”

Section: Discussionmentioning

confidence: 96%

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

et al. 2015

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Our results show that the luminal epithelial (LEP) and myoephitelial (MEP) mammary LM38-P subpopulations respond differently to ATRA, i.e., the LEP subpopulation responds with increased cell cycle arrest and apoptosis and the MEP subpopulation responds with increased senescence and adhesion, thereby decreasing its invasive capacity. Finally, we identified a third subpopulation with stem/progenitor cell characteristics within the LM38-LP mammary adenocarcinoma cell line, which appears to be non-responsive to ATRA.

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Section: Discussionmentioning

confidence: 96%

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

et al. 2015

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“…42 This was monitored by the fluorescence of the dye 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine (JC-1) wherein, JC-1 displays red fluorescence (590 nm) with normal cells (high Δψ mt ), which is caused by the spontaneous and local formation of aggregates that are associated with a large shift in the emission. Mitochondria play an essential role in the propagation of apoptosis.…”

Section: Biologymentioning

confidence: 99%

Synthesis of 2-anilinopyridyl–triazole conjugates as antimitotic agents

et al. 2015

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A series of 2-anilinopyridyl–triazole conjugates (6a–t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.1 μM. Structure–activity relationships were elucidated with various substitutions on these conjugates. Flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds (6q, 6r and 6s) effectively inhibited the microtubule assembly in human prostate cancer cells (DU-145). The docking studies showed that 6s interacts and binds efficiently with the tubulin protein at the colchicine binding site. This was further confirmed by the colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess anti-tubulin activity both in vitro and within cells as demonstrated by the ratio of soluble versus polymerized tubulin. Further the apoptotic effects of compounds were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC, mitochondrial membrane potential and DNA fragmentation analysis. Interestingly, these compounds did not affect the normal human embryonic kidney cells, HEK-293.

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“…The maintenance of mitochondrial membrane potential (∆Ψm) is significant for mitochondrial integrity and bioenergetic function . Mitochondrial changes, including loss of mitochondrial membrane potential (∆Ψm), are the key events that take place during drug‐induced apoptosis.…”

Section: Resultsmentioning

confidence: 99%

Novel menadione hybrids: Synthesis, anticancer activity, and cell‐based studies

et al. 2017

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A series of novel menadione-based triazole hybrids were designed and synthesized by employing copper-catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data ( 1 H NMR, 13 C NMR, IR, and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7), and mouse melanoma (B-16) using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity. Among the tested compounds, the triazoles 5 and 6 exhibited potent activity against all cell lines. In particular, compound 6 showed higher potency than the standard tamoxifen and parent menadione against MCF-7 cell line.Flow cytometric analysis revealed that compound 6 arrested cell cycle at G0/G1phase and induced apoptotic cell death which was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin-V-FITC assay. Thus, compound 6 can be considered as lead molecule for further development as potent anticancer therapeutic agent.

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Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells

Cited by 56 publications

References 25 publications

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid

Synthesis of 2-anilinopyridyl–triazole conjugates as antimitotic agents

Novel menadione hybrids: Synthesis, anticancer activity, and cell‐based studies

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