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Oblongifolin C inhibits metastasis by up-regulating keratin 18 and tubulins
Xiaoyu Wang1, Yuanzhi Lao1, Naihan Xu2
11] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
Abstract:
Tumor metastasis is the main cause of cancer-related patient death. In this study, we performed a wound healing migration screen to search for a metastatic inhibitor within our library of natural compounds. We found that oblongifolin C (OC), a natural compound extracted from Garcinia yunnanensis Hu, is an effective inhibitor of metastasis in human esophageal squamous carcinoma Eca109 cells. The transwell migration and matrigel invasion assay results also showed that OC inhibits the migration of Eca109 cells and HepG2 cells. OC can increase the expression of tubulin, indicating that OC inhibits metastasis via tubulin aggregation. In addition, the Western blotting, real-time PCR, and immunostaining results indicated that OC increases the expression of keratin18. Furthermore, the knockdown of keratin 18 by small interfering RNAs inhibited the expression of tubulin and increased the metastasis of cancer cells, suggesting that keratin 18 is the upstream signal of tubulin and plays a vital role in metastasis. A subsequent study in a tail vein injection metastasis model showed that OC can significantly inhibit pulmonary metastasis, as revealed by immunohistochemistry staining. Taken together, our results suggest that OC inhibits metastasis through the induction of the expression of keratin 18 and may be useful in cancer therapy.
Insights
Oblongifolin C (OC), a natural compound, effectively inhibits cancer metastasis by increasing keratin 18 and tubulin expression. This discovery offers a potential new therapy for reducing cancer spread and improving patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Tumor metastasis is a primary driver of cancer mortality.
- Identifying novel metastasis inhibitors is crucial for effective cancer therapy.
Purpose of the Study:
- To identify natural compounds that inhibit cancer cell metastasis.
- To elucidate the molecular mechanisms by which Oblongifolin C (OC) inhibits metastasis.
Main Methods:
- Wound healing migration assay, transwell migration, and matrigel invasion assays were used to assess metastatic potential.
- Western blotting, real-time PCR, and immunostaining were employed to analyze protein and gene expression.
- A tail vein injection metastasis model was utilized to evaluate in vivo efficacy.
Main Results:
- Oblongifolin C (OC) significantly inhibited migration and invasion in esophageal squamous carcinoma (Eca109) and hepatocellular carcinoma (HepG2) cells.
- OC treatment led to increased tubulin expression and aggregation, suggesting a mechanism for metastasis inhibition.
- OC upregulated keratin 18 expression, which was identified as an upstream regulator of tubulin and critical for metastasis.
Conclusions:
- Oblongifolin C (OC) effectively inhibits cancer metastasis by modulating keratin 18 and tubulin pathways.
- OC demonstrates potential as a therapeutic agent for preventing or treating cancer metastasis.
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