Sea Buckthorn-based Nano-Medicine Reduces Growth in Aggressive Breast Cancer

Jenn Hoskins
13th August, 2024

Sea Buckthorn-based Nano-Medicine Reduces Growth in Aggressive Breast Cancer

Image Source: Natural Science News, 2024

Key Findings

  • Researchers from Zhejiang Sci-Tech University developed a new treatment combining sea buckthorn polyphenols and metformin to target triple-negative breast cancer (TNBC)
  • This new treatment significantly inhibited cell growth in TNBC cell lines without harming normal cells
  • The treatment works by inducing programmed cell death in TNBC cells through specific pathways, leading to effective cancer cell elimination
Triple-negative breast cancer (TNBC) is a particularly aggressive form of breast cancer with limited treatment options. This type of cancer lacks three common receptors that are typically targeted in breast cancer therapies, making it difficult to treat. Researchers from Zhejiang Sci-Tech University have developed an innovative phyto-nanomedicine (PNM) aimed at addressing this challenge[1]. This new approach combines polyphenols extracted from sea buckthorn (SBP) with metformin (MET), a common diabetes medication known for its anticancer properties, to evaluate its anti-tumor effectiveness in TNBC. The study highlights that SBP contains 16 newly identified polyphenols, which are compounds known to regulate cell development, proliferation, and programmed cell death (PCD) effectively. When combined with metformin, this novel PNM showed significant inhibition of cell proliferation in TNBC cell lines MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%), without affecting normal murine cell development. Mechanistically, the SBP-MET PNM induces apoptosis, a form of programmed cell death, in TNBC cells through several pathways. The proteome expression profiling in vivo revealed the upregulation of the proapoptotic Bax protein and the activation of Fas signaling pathways. These pathways subsequently activate downstream Daxx and FADD proteins, which trigger Caspase-3, an essential enzyme in the apoptosis process. Caspase-3 then cleaves PARP-1 protein, leading to cell death in TNBC cells. This finding is significant as it presents a highly biocompatible treatment option that effectively induces regulated cell death (RCD) in TNBC cells in vivo, thus opening new avenues for TNBC therapy. Previous studies have shown that metformin exhibits anticancer properties by promoting ROS-dependent apoptosis through the regulation of the Mcl-1-Bim-Bak axis[2]. This aligns with the current study's findings, where metformin's role in the PNM enhances its ability to induce apoptosis in TNBC cells. Additionally, metformin has been shown to increase cellular ROS levels and exhibit anticancer activity in combination with other compounds[3]. This supports the current study's approach of combining metformin with SBP to enhance its anticancer effects. The use of CRISPR screening in previous research has identified the interplay between oncogenic and tumor suppressor pathways in TNBC, highlighting the therapeutic potential of targeting the mTOR and Hippo pathways[4]. The current study builds on this by introducing a novel combination therapy that targets these pathways through a different mechanism, involving polyphenols and metformin. Overall, the development of the SBP-MET PNM represents a promising advancement in the treatment of TNBC. By leveraging the anticancer properties of metformin and the newly identified polyphenols from sea buckthorn, this innovative approach offers a potential new therapy for a challenging and aggressive form of breast cancer.

MedicineHealthBiotech

References

Main Study

1) Hippophae Rhamnoides-derived Phytomedicine Nano-System Modulates Bax/Fas Pathways to Reduce Proliferation in Triple-Negative Breast Cancer.

Published 12th August, 2024

https://doi.org/10.1002/adhm.202401197

Related Studies

2) Bak instead of Bax plays a key role in metformin-induced apoptosis s in HCT116 cells.

https://doi.org/10.1038/s41420-021-00755-y

3) Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells.

https://doi.org/10.1038/s41598-021-93270-0

4) In vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR/Hippo targeted combination therapy.

https://doi.org/10.1038/s41467-021-23316-4


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