Black maitake induces apoptosis and enhances the efficacy of standard chemotherapy in 2D and 3D U-87 MG glioblastoma cell models.

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Citation abstract

OBJECTIVES: Glioblastoma is an aggressive primary brain tumor marked by rapid growth, invasiveness, poor prognosis, and an over 90 % tumor recurrence rate. Current radiation and chemotherapy treatments are limited by non-selectivity and toxicity, creating a need for safer complementary treatments. Historically, natural health products (NHPs) have been used medicinally across cultures for their anti-inflammatory and antioxidant effects. More recently, they have gained recognition for their selective, non-toxic properties in cancer treatment, suggesting their potential as adjuncts to conventional therapies. Black maitake ( Grifola frondosa ) extract, a well-tolerated NHP with known immunomodulatory properties, has demonstrated anticancer effects in breast cancer models. This study investigates the ability of Black Maitake Odaira Extract - Prothera (BMOE; a trade name of the extract manufactured by Shogun Maitake Canada, London, ON) to induce cell death in the U-87 MG glioblastoma cell line using 2D and 3D models, alone and in combination with the standard chemotherapy: temozolomide (TMZ).

METHODS: Apoptosis was assessed via Hoechst 33,342, annexin V, and propidium iodide staining, along with morphological analyses. Mitochondrial depolarization was measured using TMRM, cell migration was assessed via wound-healing assays, and structural integrity was evaluated using 3D spheroids.

RESULTS: BMOE, alone and with TMZ, induced dose-dependent apoptosis, mitochondrial depolarization, and impaired glioblastoma cell migration. BMOE also disrupted 3D spheroid structures and promoted nuclear condensation, consistent with apoptotic processes. Most notably, BMOE significantly enhanced the anti-cancer effects of TMZ.

CONCLUSIONS: These findings support the potential of BMOE as a complementary therapy that enhances the efficacy of current glioblastoma treatments.