A Novel Benzothiazole Derivative YLT322 Induces Apoptosis via the Mitochondrial Apoptosis Pathway In Vitro with Anti-Tumor Activity in Solid Malignancies

Song, Xian‐Rong; Xia, Yong; Wang, Ningyu; Zhang, Lidan; Xue-yin, Shi; Xu, Youzhi; Ye, Tinghong; Shi, Yu; Zhu, Yiping; Yu, Luoting

doi:10.1371/journal.pone.0063900

Cited by 18 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot analysis was performed as described previously [22]. Cells were washed with cold PBS twice and lysed in RIPA buffer after treatment with AZD4547 for 48 h and the lysates were centrifuged at 13,000 g for 15 min at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Reductions in Myeloid-Derived Suppressor Cells and Lung Metastases using AZD4547 Treatment of a Metastatic Murine Breast Tumor Model

Liu

Han

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: AZD4547, a small-molecule inhibitor targeting the tyrosine kinase of Fibroblast Growth Factor Receptors (FGFRs), is currently under phase II clinical study for human subjects having breast cancer, while the underlying mechanism remains elusive. The aim of this study is to explore the potential mechanism by which AZD4547 inhibits breast tumor lung metastases at the level of the tumor microenvironment. Methods: First, through in vitro experiments, we investigated the efficacy of the FGFRs inhibitor AZD4547 on 4T1 tumor cells for their proliferation, apoptosis, migration, and invasion. Second, by in vivo animal experiments, we evaluated the effects of AZD4547 on tumor growth and lung metastases in 4T1 tumor-bearing mice. Finally, we examined the impact of AZD4547 on the infiltration of myeloid-derived suppressor cells (MDSCs) in lung, spleens, peripheral blood and tumor. Results: Through this study we found that AZD4547 could efficiently suppress tumor 4T1 cells through restraining their proliferation, blocking migration and invasion, and inducing apoptosis in vitro. In animal model we also demonstrated that AZD4547 was able to inhibit tumor growth and lung metastases, consistent with the decreased MDSCs accumulation in the tumor and lung tissues, respectively. Moreover, the reduced number of MDSCs in peripheral blood and spleens were also observed in the AZD4547-treated mice. Importantly, through the AZD4547 treatment, the CD4⁺ and CD8⁺ T-cells were significantly increased in tumor and spleens. Conclusion: Our studies showed that AZD4547 can inhibit breast cancer cell proliferation, induce its apoptosis and block migration and invasion in vitro and suppress tumor growth and lung metastases by modulating the tumor immunologic microenvironment in vivo.

show abstract

Section: Methodsmentioning

confidence: 99%

Reductions in Myeloid-Derived Suppressor Cells and Lung Metastases using AZD4547 Treatment of a Metastatic Murine Breast Tumor Model

Liu

Han

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Benzothiazole derivatives were reported to show growth inhibition against a broad spectrum of human cancer cells and induced apoptosis of HepG2 cells in a dose- and time-dependent manner [27,28]. In addition, pyrazole nucleus was revealed to have an important role in producing anti-tumor potencies [13,29].…”

Section: Antiproliferative Activitymentioning

confidence: 99%

Design, Synthesis and Anticancer Screening of Novel Pyrazole Derivatives Linking to Benzimidazole, Benzoxazole and Benzothiazole

Abdelgawad¹,

Abdellatif²,

Ahmed³

2014

Med chem

View full text Add to dashboard Cite

Substituted aromatic amines were diazotized followed by coupling with malononitrile to afford substituted phenyl hydrazono-malononitrile compounds 2a-c. Compounds 3a-c were prepared through the reaction of substituted phenyl hydrazono-malononitriles 2a-c with phenyl hydrazine, while the reaction of compounds 2a-c with hydrazine hydrate afforded diamino compounds 4a-c. The diamino compounds 4a-c was condensed with different substituted aromatic aldehydes to yield N-benzylidine pyrazole diamines 5a-i. The structure of the newly synthesized compounds was confirmed by IR, 1 H NMR, MS spectral data and elemental analysis. Twelve novel compounds 3a-c and 5a-i were screened for their anticancer activities against breast carcinoma (T47D) and human hepatocarcinoma cell lines (Huh-7) compared with Doxorubicin. The detailed synthesis, spectroscopic data and anticancer activities of the synthesized compounds were reported.

show abstract

“…Anticancer activity on human carcinoma cell lines has been reported for a benzothiazole linked to a phthalimide moiety [15]; moreover, benzothiazole-2-thiol derivatives have been proposed as novel apoptosis inducers [16]. A novel benzothiazole derivative has been shown to induce apoptosis via the mitochondrial apoptosis pathway in vitro with antitumor activity in solid malignancies [17]. Furthermore, it has been reported that antimicrobials often induce cytotoxicity via apoptotic mechanism, thus making themselves candidates as new tools for anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity Evaluation of a Series ofN-1,3-Benzothiazol-2-ylbenzamides as Novel Apoptosis Inducers

Corbo

Carocci

Armenise

et al. 2016

Journal of Chemistry

View full text Add to dashboard Cite

A series ofN-1,3-benzothiazol-2-ylbenzamide derivatives were studied for their antiproliferative activity on human liver hepatocellular carcinoma (HepG2) and human breast cancer (MCF-7) cell lines. Most of them were found to show a prominent inhibitory effect on cell growth. Among the most active compounds,1kemerged for its proapoptotic effect that is particularly evident towards MCF-7 cancer cell lines.

show abstract

A Novel Benzothiazole Derivative YLT322 Induces Apoptosis via the Mitochondrial Apoptosis Pathway In Vitro with Anti-Tumor Activity in Solid Malignancies

Cited by 18 publications

References 34 publications

Reductions in Myeloid-Derived Suppressor Cells and Lung Metastases using AZD4547 Treatment of a Metastatic Murine Breast Tumor Model

Reductions in Myeloid-Derived Suppressor Cells and Lung Metastases using AZD4547 Treatment of a Metastatic Murine Breast Tumor Model

Design, Synthesis and Anticancer Screening of Novel Pyrazole Derivatives Linking to Benzimidazole, Benzoxazole and Benzothiazole

Antiproliferative Activity Evaluation of a Series ofN-1,3-Benzothiazol-2-ylbenzamides as Novel Apoptosis Inducers

Contact Info

Product

Resources

About