Abstract

Glioblastoma is an aggressive brain tumour with 5-year survival rates of just 6.8%, while neuroblastoma accounts for 15% of pediatric cancer deaths. Standard treatment options have limited effectiveness and lack specificity, resulting in severe adverse effects and diminished quality of life. Alternatively, natural health products, used in traditional medicines and safe for long-term consumption, may possess anticancer activity. Specifically, whole extracts of Piper longum (LPE) and Camellia sinensis (STE) have demonstrated selective antineoplastic activity in cancer. This study investigates their potential as novel therapeutics for glioblastoma and neuroblastoma which may be used alongside standard treatments. We posit these extracts exhibit both selective standalone anti-cancer activity and interact positively with chemotherapeutics, targeting the bulk tumour and cancer stem cells. Indeed, in-vitro experiments demonstrated LPE- and STE-induced apoptosis in glioblastoma and neuroblastoma, mediated by oxidative stress and mitochondrial destabilization respectively. Importantly, our extracts did not impede chemotherapeutic efficacy in combination treatments. These findings indicate the potential of STE and LPE as safe and effective adjuvant therapeutics in both glioblastoma and neuroblastoma. Their use may enable reduced chemotherapy dosages, minimizing adverse effects and providing a promising avenue for preventing cancer relapse. Further investigation, including clinical studies, is warranted to validate these therapeutic benefits.

Keywords:Apoptosis; Cancer; Glioblastoma; Natural health products; Neuroblastoma; Oxidative stress

Abbreviations: AV: Annexin V; BBB: Blood-Brain-Barrier; CSC: Cancer Stem Cell; DCF: 2,7-Dichlorofluorescein; DMSO: Dimethyl Sulfoxide; GBM: Glioblastoma; GSC: Glial Cancer Stem Cell; JNK: Jun N-terminal Kinase; LPE: Long Pepper Extract; MMP: Mitochondrial Membrane Potential; NAC: N-Acetyl Cysteine; NB: Neuroblastoma; NHP: Natural Health Product; PBS: Phosphate-Buffered Saline; PI: Propidium Iodide; ROS: Reactive Oxygen Species; STE: Synthite Tea Extract; TBST: Tris-Buffered Saline, 0.1% Tween 20 Detergent; TMRM: Tetramethylrhodamine, Methyl ester; TMZ: Temozolomide; WST: Water-Soluble Tetrazolium Salt