Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1

Abstract

Abstract. Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473).In conclusion, we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo.

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer

“…To examine how sensory neurons impact PDAC initiation and progression, we first determined if neonatal capsaicin had direct effects on pancreatic cells because previous studies using cancer-derived cell lines showed it affected apoptosis and proliferation (28)(29)(30)(31)(32)(33)(34). The neurotoxic effects of neonatal capsaicin treatment are assumed to be via binding to TRPV1, the vanilloid receptor specific for capsaicin.…”

The Potential Antitumor Effects of Capsaicin

“…Capsaicin at 5 mg/kg administered by oral gavage 3 days a week reduced 30 % the volume and weight of pancreatic tumors (Pramanik and Srivastava 2012;Zhang et al 2013) and urinary bladder tumors . Capsaicin was an extremely effective inhibitor of the cancer process, inducing apoptosis in cancer cells.…”

Anti-Cancer Effects and Mechanisms of Capsaicin in Chili Peppers

“…Several reports indicate that capsaicin exerts its inhibitory effect on proliferation of pancreatic cancer cells via ERS-mediated apoptotic pathway or the phosphoinositide 3-kinase/Akt pathway [55] [58]. Other studies elucidated that capsaicin causes ROS generation through mitochondria and depleted intracellular antioxidants resulting in mitochondrial damage and apoptosis in pancreatic cancer cells, while normal pancreatic epithelial cells were resistant to the effects of capsaicin [59].…”

“…Capsaicin, the active compound in chili peppers, has been proven to induce apoptosis in various tumors so as to enhance the therapeutic effects of chemotherapy in pancreatic cancer [55]- [57]. Several reports indicate that capsaicin exerts its inhibitory effect on proliferation of pancreatic cancer cells via ERS-mediated apoptotic pathway or the phosphoinositide 3-kinase/Akt pathway [55] [58].…”