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Purpose <p>Cutaneous melanoma, a highly aggressive skin cancer, has limited treatment options. This study explores incensole (Inc) and incensole acetate (IncA), diterpenes from <i>Boswellia</i> species, as immunomodulatory agents capable of reshaping the tumor microenvironment to suppress melanoma progression.</p> Methods <p>In vitro, Inc and IncA cytotoxicity was evaluated against SK-MEL-28 cells, HUVECs, and fibroblasts to assess tumor selectivity. SK-MEL-28 cell migration was measured to evaluate anti-metastatic potential. P53, P21, CDK2 expression, and IL-1β secretion were quantified by real-time PCR and ELISA to elucidate molecular effects. Macrophage polarization was analyzed for immunomodulation. In vivo, Inc and IncA efficacy on a B16F10 Red-FLuc model was monitored via bioluminescence, with VEGF, TNF-α, IL-6 levels and histopathology assessed.</p> Results&#xa0;and conclusion <p>Both compounds showed selective cytotoxicity against SK-MEL-28 cells. Inc induced p53-mediated cell cycle arrest and apoptosis by upregulating P21 and downregulating CDK2, while promoting M1 macrophage polarization. Both reduced M2 markers and IL-1β secretion, mitigating tumor-promoting inflammation. Migration was inhibited, with Inc outperforming IncA. In vivo, Inc significantly lowered tumor burden, metastasis, VEGF, NO, and IL-6 levels, while increasing TNF-α, immune infiltration, and apoptosis. IncA reduced IL-6 and TNF-α but had milder effects on tumor burden. Histopathology confirmed Inc’s superior immune activation and tumor suppression. Inc and IncA exhibit potent anti-melanoma effects through distinct immunomodulatory and tumor-suppressive mechanisms. Inc’s greater efficacy positions it as a lead candidate, while IncA’s subtler effects suggest potential as an adjunct therapy. These findings warrant further investigation into their combined therapeutic potential for melanoma management.</p>

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Incensole enhances anti-tumor immunity and inhibits melanoma progression by modulating macrophage polarization and suppressing metastasis

  • 期刊论文

  • 发表日期：

    2025年10月31日

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  • Fatemeh Jamshidi-adegani,
  • Juhaina Al-kindi,
  • Saeid Vakilian,
  • Fahad Al-Fahdi,
  • Raziyeh Rezaei,
  • Salim Al-Adawi,
  • Nasar Alwahaibi,
  • Asem Shalaby,
  • Ahmed Al-Harrasi,
  • Sulaiman Al-Hashmi

摘要

Purpose

Cutaneous melanoma, a highly aggressive skin cancer, has limited treatment options. This study explores incensole (Inc) and incensole acetate (IncA), diterpenes from Boswellia species, as immunomodulatory agents capable of reshaping the tumor microenvironment to suppress melanoma progression.

Methods

In vitro, Inc and IncA cytotoxicity was evaluated against SK-MEL-28 cells, HUVECs, and fibroblasts to assess tumor selectivity. SK-MEL-28 cell migration was measured to evaluate anti-metastatic potential. P53, P21, CDK2 expression, and IL-1β secretion were quantified by real-time PCR and ELISA to elucidate molecular effects. Macrophage polarization was analyzed for immunomodulation. In vivo, Inc and IncA efficacy on a B16F10 Red-FLuc model was monitored via bioluminescence, with VEGF, TNF-α, IL-6 levels and histopathology assessed.

Results and conclusion

Both compounds showed selective cytotoxicity against SK-MEL-28 cells. Inc induced p53-mediated cell cycle arrest and apoptosis by upregulating P21 and downregulating CDK2, while promoting M1 macrophage polarization. Both reduced M2 markers and IL-1β secretion, mitigating tumor-promoting inflammation. Migration was inhibited, with Inc outperforming IncA. In vivo, Inc significantly lowered tumor burden, metastasis, VEGF, NO, and IL-6 levels, while increasing TNF-α, immune infiltration, and apoptosis. IncA reduced IL-6 and TNF-α but had milder effects on tumor burden. Histopathology confirmed Inc’s superior immune activation and tumor suppression. Inc and IncA exhibit potent anti-melanoma effects through distinct immunomodulatory and tumor-suppressive mechanisms. Inc’s greater efficacy positions it as a lead candidate, while IncA’s subtler effects suggest potential as an adjunct therapy. These findings warrant further investigation into their combined therapeutic potential for melanoma management.