Capsaicin induces apoptosis in SCC‐4 human tongue cancer cells through mitochondria‐dependent and ‐independent pathways

Abstract

Although there have been advances in the fields of surgery, radiotherapy, and chemotherapy of tongue cancer, the cure rates are still not substantially satisfactory. Capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide) is the major pungent ingredient of hot chili pepper and has been reported to have an antitumor effect on many human cancer cell types. The molecular mechanisms of the antitumor effect of capsaicin are not yet completely understood. Herein, we investigated whether capsaicin induces apoptosis in human tongue cancer cells. Capsaicin decreased the percentage of viable cells in a dose‐dependent manner in human tongue cancer SCC‐4 cells. In addition, capsaicin produced DNA fragmentation, decreased the DNA contents (sub‐G1 phase), and induced G0/G1 phase arrest in SCC‐4 cells. We demonstrated that capsaicin‐induced apoptosis is associated with an increase in reactive oxygen species and Ca2+ generations and a disruption of the mitochondrial transmenbrane potential (ΔΨm). Treatment with capsaicin induced a dramatic increase in caspase‐3 and ‐9 activities, as assessed by flow cytometric methods. A possible mechanism of capsaicin‐induced apoptosis is involved in the activation of caspase‐3 (one of the apoptosis‐executing enzyme). Confocal laser microscope examination also showed that capsaicin induced the releases of AIF, ATF‐4, and GADD153 from mitochondria of SCC‐4 cells. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway

“…Cap has been previously demonstrated to inhibit the proliferation of, or induce apoptosis in, numerous varieties of human cancer, including lung, prostate, pancreatic and breast cancer, in vitro and in vivo (9–12). Cap causes tumor cell cycle arrest in S or G 1 /G 0 phase in NPC-TW 039 human nasopharyngeal carcinoma cells, MCF-7 human breast cells, BT-474 cells, SKBR-3 cells, MDA-MB231 cells and SCC-4 human tongue cells, in model systems in vitro and in vivo (13–15). Furthermore, Cap triggers apoptosis in >40 distinct tumor cell lines, primarily through the mitochondrial pathway or death receptor pathway (16).…”

The Selective Target of Capsaicin on FASN Expression and De Novo Fatty Acid Synthesis Mediated through ROS Generation Triggers Apoptosis in HepG2 Cells

“…Over the past decades, research studies have demonstrated the applications of capsaicin as a specific and potent anti-carcinogenic agent through the apoptosis pathway in both in vitro and in vivo cancer models, whereas it does not induce cytotoxicity in normal cells [3], [4], [5], [6], [7]. The mechanisms underlying capsaicin-induced apoptosis may involve multiple signaling pathways and depend upon cell types [3], [8]. Capsaicin acts as the high affinity agonist that directly binds to the transient receptor potential vanilloid subtype 1 (TRPV1) and TRPV6 receptors that belong to the transient receptor potential (TRP) superfamily of nonselective cation-channels.…”

“…Capsaicin acts as the high affinity agonist that directly binds to the transient receptor potential vanilloid subtype 1 (TRPV1) and TRPV6 receptors that belong to the transient receptor potential (TRP) superfamily of nonselective cation-channels. They are overexpressed mainly in human cancer cells compared to normal cells [4], [5], [8], [9], [10], [11], including HepG2 cells [12]. The binding of capsaicin to TRPV1 induces apoptosis via multiple mechanisms, including the generation of reactive oxygen species (ROS), such as superoxide radicals and hydrogen peroxide as well as impairment of ER calcium homeostasis.…”

Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways

“…Many studies have demonstrated that death-receptor, mitochondria and endoplasmic reticulum played an important role in apoptosis (8,9). The activation of effector caspases such as caspase-3 and -7 by initiator caspases (caspase-8 and -9) are responsible for the cleavage of cellular substrates degrading the chromosomes into nucleosomal fragments during apoptosis (10,11). Two major pathways are involved in cell apoptosis; the death receptor pathway and the mitochondria-dependent pathway.…”