Benzoxathiol derivative BOT-4-one suppresses L540 lymphoma cell survival and proliferationviainhibition of JAK3/STAT3 signaling

Abstract

Abbreviations: BOT-4-one, 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo [1,3]oxathiol-4-one; JAK, janus kinase; STAT3, signal transducer and activator of transcription 3; upd, unpaired

Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back

“…The engineered cells were then used in a high-throughput screen of a library of novel polysubstituted imidopiperidines that resulted in the identification of 2- apoptosis by downregulating the expression of STAT3-regulated cell survival genes. In another study, 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo [1,3]oxathiol-4-one (BOT-4-one), a derivative of benzoxathiol, was found to possess anticancer activity in both Drosophila Schneider and human cancer cells [27]. BOT-4-one suppressed upd-induced tyrosine phosphorylation and transcriptional activity of STAT92E in Drosophila cells.…”

“…Because dysregulation of STAT signaling is linked with BOT-4-one Inhibited tyrosine phosphorylation of STAT92E and exhibited anticancer activities in Drosophila Schneider cells [27] Methotrexate, aminopterin Inhibited the JAK-STAT pathway in Drosophila [28] FDA-approved drugs Drosophila stem cell tumors were sensitive to a wide range of drugs (gemcitabine, methotrexate, thiotepa, topotecan, rapamycin); paradoxically, a subset of drugs (actinomycin, bortezomib, paclitaxel, vincristine, vinblastine, mitomycin, daunorubicin) that inhibited growth of cancer stem cells also induced hyperproliferation of wild-type stem cells driven by the JAK-STAT pathway [21] ZD6474 Oral dose of the drug suppressed the defects associated with wild-type and oncogenic forms of dRET [31,32]; exhibited efficacy in patients with advanced MTC [33] MS0019266 Exhibited anticancer activities in Drosophila expressing oncogenic MEN2B and increased the viability of the Drosophila larvae and the number of organisms reaching the pupal and adult stages [35] Indomethacin Enhanced hAPC-induced eye defects in the fly [40] Oxazoles, thiazoles, thiazolidinedione Exhibited potent inhibitory effects on b-catenin-responsive transcription in Drosophila [42] DAPT, Cpd E, thapsigargin, cyclopiazonic acid…”

Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice

“…Benzoxathiole derivatives including 6-hydroxy-1,3-benzoxathol-2-one and BOT-4-one have been reported several biologically active properties (Goeth and Wildfeuer, 1969;Wildfeuer, 1970;Lius andSennerfeldt, 1979, Kim et al, 2008;Kim et al, 2011). Although the action mechanism of these derivatives on NF-B and JAK3/STAT3 signaling has recently defined, the molecular mechanisms underlying the pharmacological activities remain to be clarified.…”

IL-2 Enhances Cervical Cancer Cells Proliferation and JAK3/STAT5 Phosphorylation at Low Doses, While at High Doses IL-2 Has Opposite Effects

“…In consequence, we believe that the use of IL-2 by the tumor cells depletes this growth factor at the tumor site where the growth factor is absolutely needed by the tumor infiltrating lymphocytes to become cytotoxic. Therefore, our observations suggest that in cervical cancer cells, STAT5 functions downstream of JAK3 and the two phosphorylation events are related to each other (42,43). Inhibitors of JAK3 and the downregulation of JAK3 have been proposed for the treatment of leukemia (25,26,28).…”