Genomic Analysis of Pterostilbene Predicts Its Antiproliferative Effects Against Pancreatic Cancer In Vitro and In Vivo

Abstract

Background-To investigate the inhibitory role of pterostilbene in pancreatic cancer, we conducted a genomic analysis of pterostilbene-treated pancreatic cancer cells. We also investigated the effect of pterostilbene upon the carcinogenic markers, manganese superoxide dismutase, cytochrome C, Smac/DIABLO, and STAT3 phosphorylation in vitro. The antiproliferative effects of pterostilbene were further evaluated in an in vivo model.

Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In Vitro and In Vivo

“…Furthermore, PTE has been reported to decrease tumor size and prolong survival in tumor-inoculated mice [28,29,30]. In the present study, mice were administered 5% DMSO and saline or 50 mg/kg PTE via intraperitoneal injection for 14 days, resulting in a significant reduction in tumor volume with PTE treatment.…”

Pterostilbene and Cancer: Current Review

“…In vivo, oral administration of pterostilbene at 100 mg/kg/d and 500 mg/kg/d significantly inhibited tumor growth rates in xenograft mouse models without producing signs of acute toxicity. [24]. These are doses much lower than previously described in animal models.…”

“…Pterostilbene inhibits cell proliferation and promotes apoptosis in pancreatic cancer in vitro through a mitochondrially-derived mechanism of apoptosis that includes mitochondrial membrane depolarization, release of the mitochondrial proteins cytochrome c and Smac/DIABLO with subsequent activation of caspase 3/7 [24,25], It has also been shown that pterostilbene promotes apoptosis in the pancreatic cancer cell line MIA PaCa-2 through up and down-regulation of multiple apoptosis-related genes, including manganese superoxide dismutase (MnSOD), DNA-damage-inducible transcript 3 (DDIT-3), and growth differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1) [24]. Furthermore, pterostilbeneinduced up-regulation of MnSOD also translated into increased enzymatic activity within the mitochondria, further indicating a mitochondrially-derived mechanism of pterostilbene.…”

“…Pterostilbene also inhibits constitutively active JAK/ STAT3 expression, a critical carcinogenic pathway, and regulates cell cycle dysfunction in pancreatic cancer by promoting arrest of the G0/G and S phases of the cell cycle [24,25]. In vivo, oral administration of pterostilbene at 100 mg/kg/d and 500 mg/kg/d significantly inhibited tumor growth rates in xenograft mouse models without producing signs of acute toxicity.…”

A Review of Pterostilbene Antioxidant Activity and Disease Modification

“…Several studies have shown that pterostilbene inhibits pancreatic cancer in vitro and in vivo through mechanisms of mitochondrially derived apoptosis, modification of transcription factors, and inhibition of proliferation [63, 64]. Specifically, pterostilbene-induced apoptosis in the pancreatic cell lines MIA PaCa-2 and PANC-1 has been attributed to mitochondrial membrane depolarization, release of Cytochrome C, and Smac/DIABLO with subsequent activation of caspase 3/7 [63, 64].…”