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Background <p>Doxorubicin (DOX) remains a mainstay for neuroblastoma (NB) treatment, but side effects hamper efficacy. We previously showed that DOX induces SH-SY5Y NB cell angiogenesis via the PHD-2/HIF-1α axis. Adjuvant therapies offer a promising avenue to improved outcomes. Human amniotic membrane (hAM) extract (hAME) consists of various proteins that exhibit anti-cancer and anti-angiogenic properties. This study investigates hAME as a potential adjuvant for targeting NB angiogenesis when combined with DOX.</p> Methods <p>We used cellular, molecular, and biochemical assays to evaluate the antitumorigenic activities of hAME + DOX (D + E) treatment across key hallmarks of SH-SY5Y NB progression: proliferation, cell cycle, angiogenesis, invasiveness, differentiation, and cellular bioenergetics.</p> Results <p>D + E treatment significantly suppressed SH-SY5Y cell proliferation, induced cell cycle perturbations, and reduced viability, while protecting bone marrow stem cells and human skin fibroblast normal cells. D + E treatment also countered SH-SY5Y cell invasiveness and promoted a favorable mesenchymal-to-epithelial transition (MET). Importantly, D + E treatment modulated the SH-SY5Y cellular respiration, evidenced by halted glycolytic metabolism, potentially influencing a shift towards oxidative phosphorylation and boosted urea cycle progression. Mechanistically, D + E abrogated DOX's pro-angiogenic effects and inhibited SH-SY5Y cells’ neo-vascularization in a chick embryo model.</p> Conclusions <p>These findings suggest hAME as a promising adjuvant therapy for NB, potentially offering an effective and safe treatment strategy by targeting multiple hallmarks of NB.</p> Graphical Abstract <p></p>

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Amniotic membrane promotes doxorubicin potency by suppressing SH-SY5Y neuroblastoma cell angiogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月19日

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  • Ahmed M. Abou-Shanab,
  • Shaimaa Shouman,
  • Alaa E. Hussein,
  • Ola A. Gaser,
  • Shireen Magdy,
  • Eman Ashraf,
  • Radwa Ayman Salah,
  • Omaima Idris,
  • Nagwa El-Badri

摘要

Background

Doxorubicin (DOX) remains a mainstay for neuroblastoma (NB) treatment, but side effects hamper efficacy. We previously showed that DOX induces SH-SY5Y NB cell angiogenesis via the PHD-2/HIF-1α axis. Adjuvant therapies offer a promising avenue to improved outcomes. Human amniotic membrane (hAM) extract (hAME) consists of various proteins that exhibit anti-cancer and anti-angiogenic properties. This study investigates hAME as a potential adjuvant for targeting NB angiogenesis when combined with DOX.

Methods

We used cellular, molecular, and biochemical assays to evaluate the antitumorigenic activities of hAME + DOX (D + E) treatment across key hallmarks of SH-SY5Y NB progression: proliferation, cell cycle, angiogenesis, invasiveness, differentiation, and cellular bioenergetics.

Results

D + E treatment significantly suppressed SH-SY5Y cell proliferation, induced cell cycle perturbations, and reduced viability, while protecting bone marrow stem cells and human skin fibroblast normal cells. D + E treatment also countered SH-SY5Y cell invasiveness and promoted a favorable mesenchymal-to-epithelial transition (MET). Importantly, D + E treatment modulated the SH-SY5Y cellular respiration, evidenced by halted glycolytic metabolism, potentially influencing a shift towards oxidative phosphorylation and boosted urea cycle progression. Mechanistically, D + E abrogated DOX's pro-angiogenic effects and inhibited SH-SY5Y cells’ neo-vascularization in a chick embryo model.

Conclusions

These findings suggest hAME as a promising adjuvant therapy for NB, potentially offering an effective and safe treatment strategy by targeting multiple hallmarks of NB.

Graphical Abstract