Reference - Detail
| RRC ID | 89761 |
|---|---|
| Author | Wuputra K, Matsuura Y, Gushiken S, Fukuda H, Yang YH, Ku CC, Wu CC, Lin YC, Tsai YC, Wu DC, Nozaki T, Kato K, Kawaguchi A, Nagata K, Tanaka Y, Yokoyama KK. |
| Title | Natural Extracts of Alnus japonica Induce BAK-Dependent Autophagy to Inhibit Liver Cancer Stem Cell Tumorigenesis. |
| Journal | Antioxidants (Basel) |
| Abstract |
Background: Cancer stem cells (CSCs) contribute to hepatocellular carcinoma (HCC) progression and therapeutic resistance. Natural products with antioxidant and bioactive properties may offer novel strategies to suppress CSC-driven tumorigenesis. Methods: We investigated the effects of unfermented and fermented Alnus japonica bark extracts on CSC-like rG2-DC-1C cells. Cell proliferation, invasion, and xenograft tumor formation were assessed, and autophagy/apoptosis markers were analyzed. Results: Bark extracts reduced OCT4 expression, suppressed CSC proliferation and invasion, and inhibited xenograft tumor formation. Mechanistically, extracts activated BAK-dependent autophagy, evidenced by LC3B accumulation and p62 modulation, whereas diarylheptanoids Hirsutenone (Hir) and Oregonin (Ore) primarily induced apoptosis via Caspase-3 cleavage. Blocking autophagy with chloroquine or BAK knockdown reversed the anti-invasive effects of bark extracts, confirming BAK's role in CSC suppression. Component analysis suggests quercetin contributes to autophagy induction, though synergistic effects of other constituents remain possible. Conclusions: Together, these findings indicate that Alnus japonica bark extracts suppress CSC-driven liver tumorigenesis through autophagy, while Hir and Ore act via apoptosis, highlighting complementary mechanisms that broaden the therapeutic potential of this traditional medicinal plant and support further preclinical validation. |
| Volume | 15(6) |
| Published | 2026-5-29 |
| DOI | 10.3390/antiox15060685 |
| PII | antiox15060685 |
| PMID | 42351991 |
| PMC | PMC13296072 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Bluesky |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |
| DNA material | CSIV-CMV-hSox2-IRES2-Venus (RDB08323) CSIV-CMV-hSox2-IRES2-Venus (RDB08324) CSIV-CMV-hNanog-IRES2-Venus (RDB12904) pCMFlag_hsJUN (RDB06254) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |