Sesquiterpenoids are a group of naturally occurring 15-carbon isoprenoid compounds that are mainly found in higher plants, microorganism and marine life. Many of them provided encouraging leads for chemotherapeutics. In this review, the sesquiterpenoids are classified according to the ring numbering system and the functional groups presented in the core structures as acyclic, mono-, bi-, and tricyclic derivatives, and a current overview of sesquiterpenoids as potential cytotoxic anticancer agents is provided.

In lung fibrosis development, aberrant cell signals drive resident lung fibroblasts to differentiate into myofibroblasts. Recent studies suggest a role for Janus Kinase / Signal Transducer and Activator of Transcription 3 (JAK/STAT3) signaling in lung fibrosis. There are 4 JAK isomers in the JAK family (JAK1-3 and TYK2). In this study we determined whether JAK1 kinase activity influences transforming growth factor-1 (TGF-β1) induced myofibroblast transformation. Methods: Normal human lung fibroblasts (Lonza) were transfected with JAK1 siRNA in the presence or absence of TGF-β1. Cell lysates were collected following 72 hours of incubation and immunoblot or immunoprecipitation assay (IP) were performed to measure JAK1, alpha smooth muscle actin (α-SMA), phospho-STAT3 (p-STAT3), SMAD3, and p-TGF-βReceptor-1 (p-TβR1) expression. The effect of p-STAT3 stimulation on fibroblast α-SMA expression was examined after treatment with oncostatin M (OSM). Results: Silencing JAK1 by siRNA significantly augmented TGF-β1 induction of fibroblast α-SMA expression, implying a repressive role for JAK1 on myofibroblast trans-differentiation. This increased α-SMA expression via JAK1 knockdown was accompanied by p-STAT3 inactivation and elevated p-SMAD3 levels following TGF-β1 stimulation. Incubation with the TβR1 kinase inhibitor SB431542 mitigated the TGF-β1 induced α-SMA increase after JAK1 knockdown. IP for TβR1 and JAK1 provided further evidence supporting a physical interaction of the two proteins. In addition, fibroblasts cultured in plastic dishes (stiff matrix) displayed constitutive p-STAT3 expression. Loss of this constitutive p-STAT3 expression was linked to increased α-SMA expression; on the contrary, increased p-STAT3 activation by OSM was associated with decreased α-SMA expression. Conclusion: JAK1 kinase plays a pivotal role in mediating TGFβ1 induced fibroblast to myofibroblast transdifferentiation by negatively regulating TGFβ signal transduction through suppression of TβR1 and SMAD3 activation. Inactivation of p-STAT3 promotes TGF-β signal transduction, and basal level activation of p-STAT3 is necessary for maintaining the fibroblast phenotype.