D Rhamnose β‑Hederin against human breast cancer by reducing tumor‑derived exosomes

Abstract

D Rhamnose β-hederin (DRβ-H), a novel oleanane-type triterpenoid saponin isolated from the traditional Chinese medicinal plant Clematis ganpiniana, has been demonstrated to be effective against various types of tumor. However, the exact role of DRβ-H on breast cancer remains largely unresolved. In the present study, it was observed that DRβ-H exhibited anti-proliferative and pro-apoptotic activity in human breast cancer cells (MCF-7/S). DRβ-H was able to inhibit exosome secretion, and the level of exosomes was positively associated with cell growth after absorption and internalization by target breast cancer cells. By analyzing the miRNA profiles of exosomes and MCF-7/S, it was identified that several miRNAs were detected exclusively in exosomes. Knockdown of the top five exosomal miRNAs and an MCF-7/S proliferation assay indicated that exosomal miR-130a and miR-425 may enhance MCF-7/S cell viability. Target gene prediction and pathway analysis revealed the involvement of miR-130a and miR-425 in pathways associated with malignant cell proliferation. These results demonstrated that DRβ-H inhibited MCF-7/S cell growth through reducing exosome release.

The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer

“…D Rhamnose β-hederin (DRβ-H), a triterpenoid saponin, could reduce the growth and apoptosis of cancer cells by inhibiting the secretion process of exosomes. Subsequently, some specifically encapsulated miRNAs, including miR-130a and miR-425, were also downregulated [114]. Shikonin (SK) could also suppress exosome release accompanying with reduced miR-128 [115] and restrain the cancer-promoting effects of preadipocytes through disturbing miR-140/SOX9 signaling [116].…”

MicroRNA Regulation of Breast Cancer Stemness

“…However, it has been recently suggested that miRNA biosynthesis can occur in extracellular vesicles in breast cancer [ 168 ], providing a new level of complexity. In either case, treatment with compounds that stop this process can prevent breast cancer progression by reducing miRNA-derived extracellular vesicles [ 169 , 170 ]. CSCs also secrete miRNAs in extracellular vesicles [ 171 ], suggesting that the successful treatment of breast cancer may lie in the ability to stop the secretion of extracellular vesicles containing miRNAs.…”

Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

“…D Rhamnose β-hederin from the vine Clematis ganpiniana (H.Lév. and Vaniot) Tamura reduced breast cancer tumor cell exosome production, exosomes which either carry genetic cargo coding for Docetaxel chemoresistance ( Chen et al, 2018b ) or simply pro-metastatic miRNAs, like miR-130 and miR-425 ( Chen et al, 2018a ). Finally, in breast cancer cell lines, Timosaponin A-III, extracted from the plant species Anemarrhena asphodeloides Bunge, has been shown to induce the expression of miR-200c and miR-141, both of which may target c-Myc.…”