Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model

Abstract

Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 μg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 μg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death-receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis.

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

“…TRAIL binds to DRs such as DR4 and DR5 expressed on cancer cell surfaces and activates apoptotic pathways. However, tumor cells are reported to be resistant to TRAIL-mediated cell death; thus, it is important to develop new compounds to overcome this resistance through DR expression (Bousserouel et al 2013;de Jong et al 2001;Lu et al 2014;Mahmood and Shukla 2010;Szliszka et al 2012;Wiezorek et al 2010).…”

In Vitro Toxicity of Asparagus Saponins in Distinct Multidrug‐Resistant Colon Cancer Cells

“…The saponins extracted from the edible part of green A. officinalis inhibited the growth of HL-60 human leukemia cells in dose and time dependent manner, [17] while the saponin extract of white asparagus activates TNF-related apoptosisinducing ligand (TRAIL) apoptotic pathway in human colon carcinoma cells and inhibits carcinogenesis in rat preclinical model. [18] Recently, it has been reported that a mixture of steroidal saponins isolated from HT asparagus exert anticancer effects via modulation of cell cycle in G 0 /G 1 phase and triggering apoptosis in colon cancer HCT-116 cells. [19] In addition to their organoleptic, nutritional, and functional value, these asparagus from Spain may represent a new source of saponins with functional interest due to their cytotoxic activity.…”

Phytochemicals and Gastrointestinal Cancer: Cellular Mechanisms and Effects to Change Cancer Progression

“…In human colon adenocarcinoma, methanolic extracts from white asparagus have demonstrated TRAIL death receptor pathway activation leading to the activation of caspase-8 and caspase-3, and, finally, to cell death. In addition, asparagus extracts have been seen to inhibit cellular pro-inflammatory mediators like MMP7, MMP9, and TNF-α [156].…”