Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress

Abstract

Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells.

Heptaphylline Induces Apoptosis in Human Colon Adenocarcinoma Cells through Bid and Akt/NF-κB (p65) Pathways

“…Most of the cytotoxic anticancer agents in present use have been shown to induce apoptosis in cancer cells such as etoposide, capsaicin, berberine, gomisin N and doxorubicin (Ghobrial et al, 2005;Wong, 2011). The anti-cancer drug etoposide is able to induce caspase-8 processing and apoptosis in cancer cells, capsaicin induces apoptosis through cellular stress, involving mitochondria and endoplasmic reticulum in several human cancer cells, berberine, an isoquinoline alkaloid, has several pharmacological properties and can affect in different levels the mitochondrial functions, gomisin N , a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill induced apoptosis of human leukemia U937 cells and doxorubicin also induces apoptosis in many cancer cells (Kim et al, 2010;Liu et al, 2011;IP et al, 2012). In apoptotic pathways, the Bcl-2 family of proteins are significant regulators of apoptosis and include both anti-apoptotic members (such as Bcl-2, Mcl-1, survivin and Bcl-xL) and pro-apoptotic members (for example, Bax, Bak, Bad, Bid, and Bik) (Wong, 2011).…”

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“…Capsaicin inhibited cell growth and promoted apoptosis on A375 cell line on human melanoma 37,39 . Anticancer activity of capsaicin against pancreatic cancer has successfully evaluated on PANC-1 cell line where it induced G0/G1 phase cell cycle arrest and apoptosis and ultimately arrest tumour growth 32,[40][41] .…”

“…Human esophageal epidermoid carcinoma also cured by capsaicin worked on CE 81T/VGH cell lines and found that it induced apoptosis and G0/G1 phase cell cycle arrest 37 . Capsaicin inhibited cell growth and promoted apoptosis on A375 cell line on human melanoma 37,39 .…”

“…Alpha glucosidase and α-amylase inhibitory activities of capsicum was evaluated by scientists 26 It induced autophagy, induced anti-tumorigenesis, deregulation of B-catechin, and TCF dependent signaling [32][33] . Anti-cancer activity of capsaicin on human breast cancer was studied on MCF-7, T47D, BT-474, SKBR-3 and MDA-MB231 cell lines where it causes mitochondrial dysfunction 34 , increased apoptosis and arrest cell cycle into G2/M phase [35][36][37][38] . Human myeloid leukemia also recovered by capsicum and studied on HL-60, U937 and THP-1 cell lines where it enhances the apoptotic effects by activating the calciumCaMKII-Sp1 pathway 38 .…”

Anti-Cancer Effects and Mechanisms of Capsaicin in Chili Peppers

“…Recently, capsaicin is proved to have good activity for inhibiting various tumor cells [2]. Besides, capsaicin also decreased the growth of human leukemic cells [3], gastric [4], nasopharyngeal [5], prostate [6], and hepatic carcinoma cells [7] in vitro because of its ability to mediate cell cycle arrest and induce cell apoptosis.…”