Antitumor Activity of Capsaicin on Human Colon Cancer Cells in Vitro and Colo 205 Tumor Xenografts in Vivo

Abstract

Capsaicin was reported to inhibit cancer cell growth. The aim of this study was to evaluate the antitumor potential of capsaicin by studying antitumor activity in vitro as well as in vivo. The in vitro studies are to examine the effects of capsaicin on human colon cancer colo 205 cells after exposure to capsaicin. The results showed that capsaicin induced cytotoxic effects in a time- and dose-dependent manner and increased reactive oxygen species (ROS) and Ca(2+) but decreased the level of mitochondrial membrane potential (ΔΨ(m)) in colo 205 cells. Data from Western blotting analysis indicated that the levels of Fas, cytochrome c, and caspases were increased, leading to cell apoptosis. Capsaicin decreased the levels of anti-apoptotic proteins such as Bcl-2 and increased the levels of pro-apoptotic proteins such as Bax. Capsaicin-induced apoptosis in colo 205 cells was also done through the activations of caspase-8, -9 and -3. In vivo studies in immunodeficient nu/nu mice bearing colo 205 tumor xenografts showed that capsaicin effectively inhibited tumor growth. The potent in vitro and in vivo antitumor activities of capsaicin suggest that capsaicin might be developed for the treatment of human colon cancer.

The Potential Antitumor Effects of Capsaicin

“…Whereas low ROS levels are involved in normal cell events, excess ROS cause cellular damage and ultimately lead to cell death (Sinha et al 2013). The involvement of ROS in vanilloid-induced apoptosis has been demonstrated in most of the cell lines analyzed (Sanchez et al 2007;Huang et al 2009;Lu et al 2010) and revised by Surh (Surh 2002;Lu et al 2010). In recent years, a number of studies have shown that oxidative stress could cause cellular apoptosis via both the mitochondria dependent and mitochondria-independent pathways (Sinha et al 2013).…”

“…Sustained elevation in intracellular calcium concentration activates various secondary mechanisms that induce the increased production of reactive oxygen and nitrogen species and ultimately the programmed cell death. Several studies showed that capsaicin-induced apoptosis via increased Ca 2+ levels in different carcinoma cells models (Chou et al 2009;Huang et al 2009;Lu et al 2010), although the molecular mechanisms of the Ca 2+ signaling pathways leading to capsaicin-induced cell death are still misunderstood. The release of intracellular Ca 2+ may be an important regulatory factor on early apoptosis induced by capsaicin as calcium chelators prevent capsaicin-induced cell death (Lee et al 2009).…”

Preparation, characterization, and pharmacokinetics study of capsaicin via hydroxypropyl-beta-cyclodextrin encapsulation

“…It can freely dissolve in organic solvents like alcohol, diethyl ether, phenol, acetone, dioxane, methylbenzene, and aqueous alkali, but to a lesser extent in water at room temperature. CAP is associated with various complicated pharmacological actions such as the prevention and treatment of cardiovascular system diseases (Bencsik et al, 2008), anti-obesity (Joo et al, 2010), and protection of gastrointestinal tract (Szallasi & Blumberg, 1999), as well as antitumor actions (Lu et al, 2010) and analgesia (Menendez et al, 2004). However, lower water solubility and significant first pass effect of liver lead to poor in vivo bioavailability of CAP.…”

Purified Anthocyanin from in vitro Culture of Bridelia retusa (L.) Spreng. Capable of Inhibiting the Growth of Human Oral Squamous Cell Carcinoma Cells

“…The potent in vitro and in vivo antitumor properties of capsaicin revealed that capsaicin may be used for the treatment of human colon cancer. 19 Oral administration of Crocus sativus carotenoid extract rich extract inhibits the growth of mouse tumors from (sarcoma-180), Ehrlich ascitescarcinoma (EAC), Dalton's lymphoma ascites (DLA) and significantly increased the life spans of treated tumor-bearing mice. 20 Crocetin, the carotenoid constituent of saffron, has shown significant potential as an anti-tumor agent in animal models and cell line systems.…”