Dataset Information

Sulfisoxazole inhibits exosome secretion for potential breast cancer treatment

ABSTRACT: Inhibitors of the secretion of cancer exosomes, which promote cancer progression and metastasis, can not only accelerate exosome biology research but also offer therapeutic benefits for cancer patients. We identified sulfisoxazole (SFX) which inhibits exosome secretion from breast cancer cells. SFX, an FDA-approved oral antibiotic, showed significant anti-tumor and anti-metastatic effects in mouse models of breast cancer xenografts, reduced the expression of proteins involved in exosome biogenesis and secretion, and triggered co-localization of multivesicular endosomes (MVEs) with lysosomes for degradation. These findings provide a foundation for exosome-targeted cancer therapies and the mechanistic studies on exosome biology.

OTHER RELATED OMICS DATASETS IN: GSE124320

INSTRUMENT(S): Q-Tof Ultima

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Chan-Hyeong Lee

LAB HEAD: Moon-Chang Baek

PROVIDER: PXD012689 | Pride | 2019-11-13

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	181219_MB231_exo_C_1.raw.egg	Raw
	181219_MB231_exo_C_2.raw.egg	Raw
	181219_MB231_exo_C_3.raw.egg	Raw
	181219_MB231_exo_S100_1.raw.egg	Raw
	181219_MB231_exo_S100_3.raw.egg	Raw

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Publications

Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A.

Im Eun-Ju EJ Lee Chan-Hyeong CH Moon Pyong-Gon PG Rangaswamy Gunassekaran Gowri GG Lee Byungheon B Lee Jae Man JM Lee Jae-Chul JC Jee Jun-Goo JG Bae Jong-Sup JS Kwon Taeg-Kyu TK Kang Keon-Wook KW Jeong Myeong-Seon MS Lee Joo-Eun JE Jung Hyun-Suk HS Ro Hyun-Joo HJ Jun Sangmi S Kang Wonku W Seo Seung-Yong SY Cho Young-Eun YE Song Byoung-Joon BJ Baek Moon-Chang MC

Nature communications 20190327 1

Inhibitors of the secretion of cancer exosomes, which promote cancer progression and metastasis, may not only accelerate exosome biology research but also offer therapeutic benefits for cancer patients. Here we identify sulfisoxazole (SFX) as an inhibitor of small extracellular vesicles (sEV) secretion from breast cancer cells through interference with endothelin receptor A (ETA). SFX, an FDA-approved oral antibiotic, showed significant anti-tumor and anti-metastatic effects in mouse models of b ...[more]

PMID: 30918259

Similar Datasets

Project description:Background: Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA’s anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA’s anticancer action. Results: Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA’s anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. Conclusions: We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA’s anticancer action, further supporting its use in cancer therapy. Examination of small RNA populations in MCF7 cells and exosomes after DHA treatment.