Cytotoxic properties of the anthraquinone derivatives isolated from the roots of Rubia philippinensis

Abstract

BackgroundCancer is one of the most frequently occurring diseases and is the second leading cause of death worldwide. In this study, anthraquinone derivatives (Compounds 1–5) were evaluated for their anti-cancer potential against various skin and breast cancer cell lines to assess whether these anthraquinone derivatives may serve as a lead for the augmentation of anti-cancer drug.MethodsAnthraquinone derivatives, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6′-O-acetyl)-α-rhamnosyl(1 → 2)-β-glucoside (Comp 1), 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (Comp 2), and alizarin (Comp 3) were isolated from the dichloromethane fraction of the roots of Rubia philippinensis., whereas ethyl acetate fraction yielded xanthopurpurin (Comp 4) and lucidin-ω-methyl ether (Comp 5). Structures of all the isolated compounds were determined by spectral data analysis. All isolated compounds (Comp 1–5) were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against four different cancer cell lines, i.e. human melanoma (SK-MEL-5), murine melanoma (B16F10), and human breast adenocarcinoma (MCF7 and MDA-MB-231).ResultsSignificant activity of the compounds 4 and 5 was observed against the breast cancer cell line MDA-MB-231 with IC50 values of 14.65 ± 1.45 and 13.03 ± 0.33 μM, respectively. Encouragingly, IC50 values of 67.89 ± 1.02 and 79.01 ± 0.03 μM against normal kidney epithelial cells (MDCK) were also obtained for compounds 4 and 5, respectively, which indicated very low toxicity and favorable selectivity indices for compounds 4 and 5 in the range of 1.85 to 3.95 and 2.11 to 6.06 against skin cancer cell lines (SK-MEL-5, and B16F10), and breast cancer cell lines (MCF7 and MDA-MB-231), respectively.ConclusionOur results suggested that the compounds 4 (xanthopurpurin) and 5 (lucidin-ω-methyl ether) showed high selective toxicity towards breast cancer cells at lower concentrations without showing toxicity towards normal cells, thus could be of potential as new lead molecules in cancer treatment.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2253-2) contains supplementary material, which is available to authorized users.

3‐O‐acetylrubianol C (3AR‐C) induces RIPK1‐dependent programmed cell death by selective inhibition of IKKβ

“…Previously, we isolated several types of novel pentacyclic triterpenoids from Rubia philippinensis (R. philippinensis) including lignans, cyclopeptides, and anthraquinones. 28,29 In the present study, we examined 17 types of pentacyclic triterpenoids isolated from R. philippinensis, and identified 3-Oacetylrubianol C (3AR-C) as a novel arborinane triterpenoid with the ability of inducing RIPK1-dependent cell death by selectively inhibiting the catalytic activity of IKKβ independent of NF-κB. These findings provide the basis for further development of 3AR-C as a pharmacological agent for promoting the therapeutic efficacy of TNF.…”

“…However, there has been little or no effort toward the efficacy of pentacyclic triterpenoids against TNF‐targeted biologics, especially regarding RIPK1‐dependent cell death. Previously, we isolated several types of novel pentacyclic triterpenoids from Rubia philippinensis ( R. philippinensis ) including lignans, cyclopeptides, and anthraquinones . In the present study, we examined 17 types of pentacyclic triterpenoids isolated from R. philippinensis, and identified 3‐ O ‐acetylrubianol C (3AR‐C) as a novel arborinane triterpenoid with the ability of inducing RIPK1‐dependent cell death by selectively inhibiting the catalytic activity of IKKβ independent of NF‐κB.…”

Cytotoxic Activity of Christia vespertilionis Root and Leaf Extracts and Fractions against Breast Cancer Cell Lines

“…The tentative assignment of compounds (Table 3) suggests the presence of flavonoids, coumarins and quinone. Polyphenols especially flavonoids and coumarins have been reported to demonstrate anti-proliferative effects as well as high antioxidative strength while quinone, a minor class compound is also valued for its high antioxidant and anti-cancer properties, especially toward breast cancers [28,40,41]. The finding suggests that the significant cytotoxic effects reported in both the active extract and fraction was due to presence of polyphenolic compounds.…”

Accelerated degradation of cFLIPL and sensitization of the TRAIL DISC-mediated apoptotic cascade by pinoresinol, a lignan isolated from Rubia philippinensis

“…Pinoresinol was isolated from our chemical study on Rubia philippinensis , as described previously 17 . Briefly, a methylene chloride (CH 2 Cl 2 )-soluble fraction (50 g) was prepared from solvent extraction of R. philippinensis extract (150 g) using CH 2 Cl 2 and water.…”