Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency. Furthermore, strigolactone analogs inhibited growth and survival of colon, lung, prostate, melanoma, osteosarcoma and leukemia cancer cell lines. To further examine the anti-cancer activity of SLs in vivo, we have examined their effects on growth and viability of MDA-MB-231 tumor xenografts model either alone or in combination with paclitaxel. We show that strigolactone act as new anti-cancer agents in inhibition of breast cancer in xenograft model. In addition we show that SLs affect the integrity of the microtubule network and therefore may inhibit the migratory phenotype of the highly invasive breast cancer cell lines that were examined.
In the combination antiretroviral era, there are limited data regarding the pathogenesis of histoplasmosis immune reconstitution inflammatory syndrome (IRIS) in people with HIV. We immunologically characterized ten cases of histoplasmosis, four of whom developed histoplasmosis IRIS. CD4+ T-cells in histoplasmosis IRIS demonstrated a significant polyfunctional cytokine response to histoplasma antigen.
Strigolactones (SLs) are a novel class of phytohormones that regulates shoot branching patterns and above-ground plant architecture by inhibiting the outgrowth of axillary lateral buds or meristems. The SL analogues (SLAs) inhibit the growth and survival of a wide array of cancer-derived cell lines including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while minimally affecting normal cultured cells. Interestingly, cancer cells with high metastatic potential are more sensitive to the inhibitory effect of SLAs than less aggressive cells. Treatment of cancer cells with SLAs leads to the activation of stress-related signaling including p38MAPKs and JNK1/2, and disrupt the microtubule network. Furthermore, a reduction in acetylated-alpha-tubulin was observed in SLA-treated MDA-MB-231 cells. Microtubules dynamics has been proposed as one of the mechanisms that regulate cell migration by acting on lamellipodia formation. The ECIS invasion assay data suggests that even at low concentration of SLA and as soon as 6 hours, SLAs suppress MDA-MB-231 cells’ ability to invade the HUVEC monolayer. To further examine the effect of SLAs on the invasive and metastatic behaviors of cancer cells in vivo, fluorescently labeled MDA-MB-231 cells were used as xenograft models in zebrafish. Embryos injected with MDA-MB-231 cells showed 66.6% metastasis in vehicle treated control fishes, as compared to 22.85% in SLAs treated fishes. This suggests that SLAs are potent inhibitors of cancer dissemination and metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Kira Lin, Christopher Grivas, Elema Boru, Yaron Dayani, Eric Berens, Anna T. Riegel, Eric Glasgow, Ronit I. Yarden. Utilizing zebrafish to study the effect strigolactone on breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5122. doi:10.1158/1538-7445.AM2017-5122
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.