Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells.

Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevertheless, the senescence-associated secretion phenotype (SASP) promotes chronic inflammation of the cancer microenvironment and further accelerates the progression of tumors. Therefore, inducing the senescence of cancer cells and inhibiting the production of SASP factors during anticancer treatment have become effective therapeutic strategies to improve the anticancer effect of drugs. Here we reported that SCLC cells treated with an FDA-approved HDAC inhibitor SAHA underwent senescence and displayed remarkable SASP. In particular, SAHA promoted the formation of cytoplasmic chromatin fragments (CCFs) in SCLC cells. The increased CCFs in SAHA-treated SCLC cells were related to nuclear porin Tpr, which activated the cGAS-STING pathway, and promoted the secretion of SASP in cancer cells. Inhibition of EZH2 suppressed the increase of CCFs in SAHA-treated SCLC cells, weakened the production of SASP, and increased the antiproliferative effect of SAHA. Overall, our work affords new insight into the secretion of SASP in SCLC and establishes a foundation for constructing a new therapeutic strategy for SCLC patients.

The Interaction of the Senescent and Adjacent Breast Cancer Cells Promotes the Metastasis of Heterogeneous Breast Cancer Cells through Notch Signaling.

Chemotherapy is one of the most common strategies for tumor treatment but often associated with post-therapy tumor recurrence. While chemotherapeutic drugs are known to induce tumor cell senescence, the roles and mechanisms of senescence in tumor recurrence remain unclear. In this study, we used doxorubicin to induce senescence in breast cancer cells, followed by culture of breast cancer cells with conditional media of senescent breast cancer cells (indirect co-culture) or directly with senescent breast cancer cells (direct co-culture). We showed that breast cancer cells underwent the epithelial-mesenchymal transition (EMT) to a greater extent and had stronger migration and invasion ability in the direct co-culture compared with that in the indirect co-culture model. Moreover, in the direct co-culture model, non-senescent breast cancer cells facilitated senescent breast cancer cells to escape and re-enter into the cell cycle. Meanwhile, senescent breast cancer cells regained tumor cell characteristics and underwent EMT after direct co-culture. We found that the Notch signaling was activated in both senescent and non-senescent breast cancer cells in the direct co-culture group. Notably, the EMT process of senescent and adjacent breast cancer cells was blocked upon inhibition of Notch signaling with N-[(3,5-difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester (DAPT) in the direct co-cultures. In addition, DAPT inhibited the lung metastasis of the co-cultured breast cancer cells in vivo. Collectively, data arising from this study suggest that both senescent and adjacent non-senescent breast cancer cells developed EMT through activating Notch signaling under conditions of intratumoral heterogeneity caused by chemotherapy, which infer the possibility that Notch inhibitors used in combination with chemotherapeutic agents may become an effective treatment strategy.

Isolation and identification of attractants from the pupae of three lepidopteran species for the parasitoid Chouioia cunea Yang.

BACKGROUND: Chouioia cunea Yang (Hymenoptera: Eulophidae) is a parasitic wasp and natural enemy of several lepidopteran pests during their pupal stage. The volatiles from pupae of three hosts, Hyphantria cunea (Arctiidae), Antheraea pernyi (Saturniidae) and Lymantria dispar (Erebidae), were analyzed and compared to elucidate the chemical cues used by C. cunea to locate its hosts. RESULTS: The attraction of C. cunea to H. cunea pupae has no obvious association with the types of plant leaves consumed by H. cunea before pupation. C. cunea exhibited the strongest attraction to the pupae of H. cunea, followed by those of A. pernyi and L. dispar based on behavioral experiments. Gas chromatography-mass spectrometry and GC-electroantennography (GC-EAD) analyses showed that these three host pupae consisted of essentially the same active volatile components but at different relative amounts. Active components derived from these pupae by GC-EAD were alkanes from C12 to C27, and C. cunea showed different levels of attraction to different single compounds. CONCLUSION: Host location by C. cunea primarily depends on common compounds emanating from the pupae of several host species. The relative amount of each component varies across host species, guiding host preferences by C. cunea. Optimal blends of several components were identified. Understanding the chemical cues used by C. cunea to locate its host could increase the possibility of developing attractants for parasitic wasps and subsequently increasing the parasitism rate of C. cunea on various hosts. © 2019 Society of Chemical Industry.

CcOBP2 plays a crucial role in 3-carene olfactory response of the parasitoid wasp Chouioia cunea.

Chouioia cunea (Yang) is a pupal parasitoid wasp and this species is able to seek host insects depending on its olfactory system. However, the molecular mechanism of the olfactory system in the C. cunea is still limited. To identify putative semiochemicals bound to CcOBP2, a protein specifically expressed in antennae, 14 compounds from the pupae of H. cunea and 11 common volatile compounds from plants were selected for competitive fluorescence binding assay. The result of the binding assay showed that five compounds were able to bind toCcOBP2. The electroantennogram (EAG) demonstrated that the antennae had a significant response to the 3-Carene, a bicyclic monoterpene, and C. cunea could be obviously attracted by this compound. The behavioral response to 3- carene was dramatically weakened when CcOBP2 was specifically knocked down. The molecular docking result indicated that several amino acids especially Ile-81, Val-122, Phe-123 of CcOBP2 were responsible for binding to 3-Carene. Furthermore, there was a repellent effect on the host H. cunea with the treatment of the 3-Carene. This study illustrated that CcOBP2 might be a crucial protein involved in the olfactory signaling pathway and the 3-Carene, secreted from plants, could probably have a potential role in repelling pests as well as attracting natural enemies.