Potent Antitumor Effects of a Combination of Three Nutraceutical Compounds.[Pubmed: 30111862]

Head and neck squamous cell carcinoma (HNSCC) is associated with low survival, and the current aggressive therapies result in high morbidity. Nutraceuticals are dietary compounds with few side effects. However, limited antitumor efficacy has restricted their application for cancer therapy. Here, we examine combining nutraceuticals, establishing a combination therapy that is more potent than any singular component, and delineate the mechanism of action. Three formulations were tested: GZ17-S (combined plant extracts from Arum palaestinum, Peganum harmala and Curcuma longa); GZ17-05.00 (16 synthetic components of GZ17-S); and GZ17-6.02 (3 synthetic components of GZ17S; curcumin, harmine and isovanillin). We tested the formulations on HNSCC proliferation, migration, invasion, angiogenesis, macrophage viability and infiltration into the tumor and tumor apoptosis. GZ17-6.02, the most effective formulation, significantly reduced in vitro assessments of HNSCC progression. When combined with cisplatin, GZ17-6.02 enhanced anti-proliferative effects. Molecular signaling cascades inhibited by GZ17-6.02 include EGFR, ERK1/2, and AKT, and molecular docking analyses demonstrate GZ17-6.02 components bind at distinct binding sites. GZ17-6.02 significantly inhibited growth of HNSCC cell line, patient-derived xenografts, and murine syngeneic tumors in vivo (P < 0.001). We demonstrate GZ17-6.02 as a highly effective plant extract combination and pave the way for future clinical application in HNSCC.

Role of fungal-induced stress in biochemical and phytochemical profiling of Peganum harmala.[Pubmed: 29685022]

The current study was designed to evaluate bioactive compounds under the influence of biotic stress on seedlings of Peganum harmala. Biologically active compounds were determined by using different techniques. The HPLC and GC-MS analyses detected the significant amount of phenolic acids and active biological compound. Total protein content, activity of proteases, α-amylases, catalases and peroxidases were observed to be accelerated under fungal stress. The seedling extracts exhibited prominent antifungal and antimicrobial activity against selected strains. The present study showed that P. harmala is a good candidate to be used in natural therapies and medicine.

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK.[Pubmed: 29510387]

Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity.