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Published on: June 9, 2023
Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Breast Cancer Effect via
Yue Yang1, Ting Fang1,2, Yi-Lan Cao3
1Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Insights
This study identifies an optimal ratio of Hedyotis diffusa and Scutellaria barbata extracts, revealing EA11 as a potent breast cancer treatment. EA11 targets key molecular pathways, offering a promising therapeutic candidate.
Area of Science:
- Phytochemistry
- Oncology
- Molecular Biology
Background:
- Hedyotis diffusa (HD) and Scutellaria barbata (SB) are used in Traditional Chinese Medicine for cancer treatment.
- The optimal ratio and molecular mechanisms of the HD-SB couplet for breast cancer remain unclear.
Purpose of the Study:
- To determine the optimal ratio of HD and SB for anti-breast cancer activity.
- To investigate the molecular mechanisms of the active fraction EA11 against breast cancer.
Main Methods:
- Aqueous extracts of HD, SB, and their combinations (HS11, HS12, HS21) were tested against 4T1 breast cancer cells.
- The ethyl acetate fraction (EA11) from the optimal ratio (HS11) was further analyzed in vitro and in vivo.
- Techniques included colony formation assays, flow cytometry, western blot, ELISA, and qRT-PCR.
Main Results:
- HS11 demonstrated the highest efficacy in suppressing 4T1 cell proliferation and tumor growth.
- EA11 showed superior antiproliferative and antitumorigenic effects compared to HS11.
- EA11 inhibited colony formation, induced apoptosis, and modulated key proteins (PDE7B, PD-L1, β-catenin, cyclin D1) and miR-200c expression.
Conclusions:
- EA11 effectively prevents breast tumor development by targeting the miR-200c-PDE7B/PD-L1-AKT/MAPK axis.
- EA11 shows potential as a therapeutic candidate for breast cancer treatment.
Background:
Hedyotis diffusa (HD) Willd. and Scutellaria barbata (SB) D. Don in different ratios have been frequently used to treat various cancers in clinical Traditional Chinese Medicine prescriptions. However, the optimal ratio, active fraction, and molecular mechanisms associated with the anti-breast cancer role of this herbal couplet have not been elaborated.
Methods:
To screen out the optimal ratio of this herbal couplet, we compare aqueous extracts of HD, SB, or HD plus SB in different weight ratios (HS11, HS12, HS21) for their anticancer effects on murine breast cancer 4T1 cells in vitro and in vivo. EA11, the ethyl acetate fraction from HS11 (the aqueous extract of the couplet at an equal weight ratio), is further assessed for its antiproliferative effect as well as the antitumorigenic impact with the aid of immunocompetent mice. Colony formation, flow cytometry, western blot, ELISA, and qRT-PCR are used to elucidate mechanisms underlying EA11-led effects.
Results:
HS11 presents the most potential suppression of 4T1 cell proliferation and tumor growth among these aqueous extracts. The comparison results show that EA11 is more effective than HS11 in vitro and in vivo. EA11 inhibits colony formation and induces apoptosis in a concentration-dependent manner. EA11 reduces the protein expressions of PDE7B, PD-L1, β-catenin, and cyclin D1 while elevating the concentration of cellular cAMP and miR-200c expression in 4T1 cells. Additionally, EA11 exerts its anticancer effect partially via the inactivation of MAPK and AKT signaling pathways.
Conclusions:
This study implicates that EA11 prevents breast tumor development by interfering with the miR-200c-PDE7B/PD-L1-AKT/MAPK axis. EA11 may represent a potential therapeutic candidate for breast cancer.
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