Evaluation of Anti-Inflammatory and Anti-Proliferative Effect of Hydroxy-, Keto-, and Epoxy-Carotenoids in RAW 264.7 and HL-60 Cells

Abstract

Aim of the study was to investigate efficiency of hydroxy (lutein, LUT), Keto-(astaxanthin, AST) and epoxy-(fucoxanthin, FUCO) carotenoids on molecular/biochemical events in proliferation of RAW 264.7 and HL-60 cells. Lipopolysaccharide (LPS) induced RAW 264.7 cells treated either with 20 µM of LUT or AST or FUCO or without carotenoid for 12 h, and studied their differential influence on toxicity, inflammatory markers and nuclear factor-κB p65 (NF-κB p65) expression levels. Similarly, HL-60 cells treated for 48 h and evaluated cytotoxicity and apoptosis inducing activity. It was observed, carotenoids treatment decreased cytotoxicity of LPS induced inflammation in macrophages. Among carotenoids, FUCO protects cytotoxicity by 10.7 and 15.8% than AST and LUT, respectively. Likewise, carotenoids treatments reduced Nitric oxide (NO), Prostaglandin E 2 (PGE 2 ) and NF-κB p65 levels than LPS treated group, while FUCO shown to be superior to control markers of inflammation than AST and LUT. Similarly, in case of HL-60 cells, FUCO significantly reduced cell viability by 16.4 and 33.4% than AST and LUT, respectively. Further, increased apoptosis of HL-60 positively correlates with decreased glutathione, and increased malondialdehyde and oxidative stress in cells treated with FUCO than AST and LUT. Also, typical apoptotic morphological changes were observed in FUCO treated cells than other oxygenated carotenoids. These differences among oxygenated carotenoids may be due to functional group and reactivity with the cells. Further, we presumed that an increase in the number of oxygen or hydroxyl groups in the carotenoids may decide the bioactivity. This study provides a greater insight of oxygenated carotenoids to combat chemoprevention of cancers originating from inflammation.

Selective Cytotoxic Effect of Astaxanthin on Human Lung and Colon Cancer Cells

“…Studies in this area have become very popular in recent years and the anticancer activity of many natural compounds has been demonstrated by experimental studies (Jyonouchi et al, 2000). Dietary carotenoids have gained nutritional importance due to their important role in reducing cardiovascular disease, cancer, obesity and age-related degenerative diseases (Vijay et al, 2016). ASX is a ketocarotenoid red pigment commonly found in nature, especially in microalgae, red yeast and some marine animals, such as salmon, shrimp, lobster and crayfish, and has higher antioxidant activity than other carotenoids, vitamins and phytochemicals (Kavitha et al, 2013;Vijay et al, 2016).…”

“…Dietary carotenoids have gained nutritional importance due to their important role in reducing cardiovascular disease, cancer, obesity and age-related degenerative diseases (Vijay et al, 2016). ASX is a ketocarotenoid red pigment commonly found in nature, especially in microalgae, red yeast and some marine animals, such as salmon, shrimp, lobster and crayfish, and has higher antioxidant activity than other carotenoids, vitamins and phytochemicals (Kavitha et al, 2013;Vijay et al, 2016). ASX is therefore seen as an important potential treatment tool for various chronic diseases, including cancer (Shao et al, 2016).…”

“…In previous studies investigating the cytotoxic effect of ASX on various cancer cells, Anderson (2005) demonstrated that ASX decreases the growth of prostate cancer (LNCaP) cells through inhibited the activity of 5α-reductase, while Lim et al (2011) reported that ASX inhibits the proliferation of esophageal cancer (TE-4) cells in a dose-dependent manner via induced caspase-dependent apoptosis and the cell cycle arrest. through arrested the cycle at G1 phase, while Vijay et al (2016) reported that ASX exhibits antiproliferative effect on human leukemia (HL-60) cells through inducing oxidative stress. Chen et al (2017) demonstrated that ASX inhibits the growth and metastasis of human melanoma (A2058 and A375) cells through inducing apoptosis and cell cycle arrest, while Kowshik et al (2019) reported that ASX shows cytotoxic effect on human oral squamous cell carcinoma (SCC131 and SCC4) cells through inducing ROS-independent mitochondrial apoptosis pathway.…”

“…Carotenoids are synthesized de novo by some microorganisms, plants and algae. In nature, there are more than 700 carotenoids and which are classified as carotenes and xanthophylls (Vijay et al, 2016). Astaxanthin (ASX), a xanthophyll carotenoid, is chemically defined as 3,3'-dihydroxy-β,β'-carotene-4,4'dion (Ekpe et al, 2018).…”