In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-ethyl-trans-stilbene (DETS) Isolated from Bacillus cereus as a Potent Candidate against Malignant Melanoma

Abstract

3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 μM] followed by cervical [HeLa-46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS in A375 cells (IC50-24.01 μM), with that in SK-MEL-2 (IC50-67.6 μM), another melanoma cells which highly over-express MITF-M. The compound arrests the cells at S-G2 transition state of the cell cycle, as resveratrol. Our results indicate that DETS is a powerful antioxidant, having anticancer efficacy comparable with that of resveratrol, and is a potential candidate to be explored by in vivo studies and in-depth mechanistic evaluation. To our knowledge, this is the first report on the antioxidant and anticancer properties of DETS.

Phenolic Fractions from Vaccinium vitis-idaea L. and Their Antioxidant and Anticancer Activities Assessment

“…This is in accordance with Csepregi et al, who pointed out that strong antioxidant activity, particularly determined by FRAP assay, is positively associated with the presence of catechol structure in ring-B and 3-hydroxyl group in ring-C of catechins and flavonols [ 59 ]. The strongest correlation between values of FIC assay and anticancer activity against malignant melanoma cancer cell line—also results of the previous study—indicates that chelating agents may play an important role in reducing the concentration of the catalyzing transition metals in ROS-mediated melanoma carcinogenesis [ 60 ]. The anticancer effect on lingonberry fractions was not related to the doubling time of cell lines.…”

Autophagy: In the cROSshairs of cancer

“…Preclinical studies have demonstrated that antioxidant supplementation leads to selective melanoma cell death through increased ROS-scavenging activity mediated by elevated SOD and catalase activity [35-37]. By contrast, dietary polyphenol antioxidants such as like resveratrol, tocopherol, and quercetin exert direct ROS-scavenging activity and have produced highly variable preclinical and clinical outcomes [38].…”

Isolation and Identification of Antimicrobial Compounds from Bacillus Cereus Obtained from Soil

“…It down-regulates the expression status of major molecules contributing to melanoma progression and arrests the cells at S-G2 transition state of the cell cycle. (Nath et al, 2016). In another study, the antibiotic 3,5-dihydroxy-4-ethyl-trans-stilbene ES produced by Xenorhabdus luminescens was found to be effective against both gram-positive and some gram-negative bacteria.…”