Phallus indusiatus Extracts Promoted MCF-7 Apoptosis Under TNFα-induced Tumor Microenvironment by Attenuating NF-kappaB and Akt Activation

Asian Pac J Cancer Prev. 2025 Feb 1;26(2):479-487. doi: 10.31557/APJCP.2025.26.2.479.

Abstract

Objective: To evaluate the anti-inflammatory and anticancer effects of Phallus indusiatus extracts, particularly in modulating inflammatory microenvironments and sensitizing lapatinib-induced cytotoxicity in breast cancer cells.

Methods: Phallus indusiatus (bamboo mushroom) extracts were prepared using water extraction from fresh and dried specimens. The anti-inflammatory effects were assessed using RAW246.7 cells by measuring NO production, while cytotoxicity and proliferation effects were evaluated in MCF-7 and MCF-10A breast cell lines. To mimic the inflammatory microenvironment of breast cancer, MCF-7 cells were treated with TNFα to induce lapatinib resistance. The effects of the extracts on cell viability, apoptosis, and NF-kappaB signaling were evaluated under inflammatory microenvironment-mimicking conditions. Co-treatment with lapatinib and the extracts was analyzed for synergistic cytotoxic effects and pathway modulation.

Results: P. indusiatus extracts demonstrated anti-inflammatory effects by reducing NO production in RAW246.7 cells. The extracts showed no cytotoxicity on MCF-7 and MCF-10A cells, with an observed proliferation increase in MCF-10A but not MCF-7. Under inflammatory microenvironment-mimicking conditions induced by TNFα, the extracts slightly reduced MCF-7 cell viability in a dose-dependent manner. Additionally, the extracts sensitized lapatinib-induced cytotoxicity by increasing apoptotic cell populations. Mechanistically, co-treatment with the extracts attenuated AKT and NF-kappaB activation in a dose-dependent manner.

Conclusion: These findings highlight the potential of P. indusiatus extracts as supplementary food for breast cancer patients, particularly in inflammatory microenvironment conditions.

Keywords: Apoptosis; Inflammation; Phallus indusiatus; breast cancer; microenvironment.

MeSH terms

  • Agaricales* / chemistry
  • Apoptosis* / drug effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • NF-kappa B* / metabolism
  • Plant Extracts* / pharmacology
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Tumor Microenvironment* / drug effects
  • Tumor Necrosis Factor-alpha* / pharmacology

Substances

  • Tumor Necrosis Factor-alpha
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Plant Extracts