β‐Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav‐1/AKT/NF‐κB Signaling Pathway

Abstract

β-carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β-carotene has an antitumor effect. However, the efficacy of β-carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β-carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin-1 (Cav-1) protein. Cav-1 protein was expressed only in ESCC cells, not in Het-1A cells. Moreover, β-carotene triggered apoptosis, induced cell cycle G0⁄G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β-carotene on the Cav-1-mediated AKT/NF-κB pathway. The results showed that the level of AKT and NF-κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl-2 ratio. Correspondingly, the activity of Caspase-3 was also enhanced. These data suggest that β-carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells.

Binding studies and biological evaluation of β-carotene as a potential inhibitor of human calcium/calmodulin-dependent protein kinase IV

“…It is well ingrained that cancerous cells have ability of evade apoptosis which is a hallmark of cancer [51]. Our results validated the recent finding suggested that β-carotene has anti-tumor potential and inhibits the growth of esophageal squamous cell carcinoma (ESCC) ESCC cells and eventually induces apoptosis [31]. To assess whether the inhibition of CAMKIV by β-carotene has any effect on cell apoptosis, HuH7 and HEK293-T cell lines were incubated with β-carotene with increasing concentration.…”

“…Here, we used a natural compound β-carotene, a member of the carotenoid family, which has antioxidant activity and could rescue the risk of certain cancers [30]. Recent studies suggested that β-carotene has anti-tumor potential and inhibits the growth of esophageal squamous cell carcinoma cells and eventually induces apoptosis [31]. β-carotene also showed anti-cancer stem cells activity in neuroblastoma [32].…”

β-carotene provides neuro protection after experimental traumatic brain injury via the Nrf2–ARE pathway

“…The antioxidant properties of β -carotene have been demonstrated in previous studies (Obulesu et al, 2011;Zhu et al, 2016). We demonstrated that in TBI mouse models, β -carotene could (1) to a certain degree, reduce brain injury and improve neurological function after TBI (Fig.…”

Marked Inhibition of Cellular Proliferation in the Normal Human Esophageal Epithelial Cells and Human Esophageal Squamous Cancer Cells in Culture by Carotenoids: Role for Prevention and Early Treatment of Esophageal Cancer

“…The molecular mechanism of carotenoids in isolated human cell culture has been studied in some details. These studies have shown that carotenoids exert their protective effect through following mechanisms: 1) causing cell cycle arrest in G1/G0 phase by down-regulating the levels of Cyclin D1 (Malumbres et al, 2009); 2) induction of apoptosis by down-regulating the levels of Survivin (Kato et al, 2001;Zhu et al, 2016); 3) enhanced cellular gap junction communication (Bertram et al, 2004) and 4) anti-angiogenic effect through modulation of various cytokines (decreased levels of IL-6, IL-1b, TNF-a, and GM-CSF and increased level of IL-2 and TIMP-1) (Guruvayoorappan et al, 2007). We did not study the mechanism of cellular inhibition and induction of DNA damage by carotenoids in our cell cycle.…”