4.6 Article

Identification of an ergosterol derivative with anti-melanoma effect from the sponge-derived fungus Pestalotiopsis sp. XWS03F09

Journal

FRONTIERS IN MICROBIOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2022.1008053

Keywords

melanoma; ergosterol; antitumor; mitochondrial apoptosis; OBSCN

Categories

Funding

  1. National Natural Science Foundation of China [82003716]
  2. Sichuan Science and Technology Department Project [2020YJ0191, 2021YFH0145, 2021YJ0123]
  3. Natural Science Foundation of Sichuan Province [2022NSFSC0109]
  4. Luzhou Municipal People's Government-Southwest Medical University Science and Technology Strategic Cooperation Project [2019LZXNYDJ08]

Ask authors/readers for more resources

A study has found that LH-1, a type of ergosterol extracted from marine fungus, has the potential to treat malignant melanoma. The research results show that LH-1 can inhibit the proliferation and migration of melanoma cells, induce cell apoptosis, and suppress melanoma growth. Furthermore, LH-1 does not have significant toxic effects on normal tissues.
It is difficult to treat malignant melanoma because of its high malignancy. New and effective therapies for treating malignant melanoma are urgently needed. Ergosterols are known for specific biological activities and have received widespread attention in cancer therapy. Here, LH-1, a kind of ergosterol from the secondary metabolites of the marine fungus Pestalotiopsis sp., was extracted, isolated, purified, and further investigated the biological activities against melanoma. In vitro experiments, the anti-proliferation effect on tumor cells was detected by MTT and colony formation assay, and the anti-metastatic effect on tumor cells was investigated by wound healing assay and transwell assay. Subcutaneous xenograft models, histopathology, and immunohistochemistry have been used to verify the anti-tumor, toxic, and side effect in vivo. Besides, the anti-tumor mechanism of LH-1 was studied by mRNA sequencing. In vitro, LH-1 could inhibit the proliferation and migration of melanoma cells A375 and B16-F10 in a dose-dependent manner and promote tumor cell apoptosis through the mitochondrial apoptosis pathway. In vivo assays confirmed that LH-1 could suppress melanoma growth by inducing cell apoptosis and reducing cell proliferation, and it did not have any notable toxic effects on normal tissues. LH-1 may play an anti-melanoma role by upregulating OBSCN gene expression. These findings suggest that LH-1 may be a potential for the treatment of melanoma.

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