Xanthone and Benzophenone Glycosides from the Stems of Cratoxylum formosum ssp. pruniflorum

Duan, Yinghui; Dai, Yi; Wang, Guanghui; Chen, Haifeng; Gao, Hao; Chen, Jiebo; Yao, Xin‐Sheng; Zhang, Xiaokun

doi:10.1248/cpb.59.231

Cited by 22 publications

(11 citation statements)

References 22 publications

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“…Previously, benzophenone glycosides that inhibited leukemia L1210 viability [35] were identified in a 60% ethanol extract from CF stems [10,36]. Xanthones, anthraquinones, and cochinchinone were identified in dichloromethane extracts of CF roots and bark [13,37], and quercetin, xanthones, and mangiferin were found in CF leaves and stem [38].…”

Section: Discussionmentioning

confidence: 99%

Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) extract induces apoptosis in human hepatocellular carcinoma HepG2 cells through caspase-dependent pathways

2014

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BackgroundCratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) (CF) has been used for treatment of fever, cough, and peptic ulcer. Previously, a 50% ethanol-water extract from twigs of CF was shown highly selective in cytotoxicity against cancer cells. This study aims to investigate the molecular mechanisms underlying the apoptosis-inducing effect of CF.MethodsThe cytotoxicity of CF was evaluated in the human hepatocellular carcinoma (HCC) HepG2 cell line in comparison with a non-cancerous African green monkey kidney epithelial cell line (Vero) by a neutral red assay. The apoptosis induction mechanisms were investigated through nuclear morphological changes, DNA fragmentation, mitochondrial membrane potential alterations, and caspase enzyme activities.ResultsCF selectively induced HepG2 cell death compared with non-cancerous Vero cells. A 1.5-fold higher apoptotic effect compared with melphalan was induced by 120 μg/mL of the 50% ethanol-water extract of CF. The apoptotic cell death in HepG2 cells occurred via extrinsic and intrinsic caspase-dependent pathways in dose- and time-dependent manners by significantly increasing the activities of caspase 3/7, 8, and 9, decreasing the mitochondrial membrane potential, and causing apoptotic body formation and DNA fragmentation.ConclusionsCF extract induced a caspase-dependent apoptosis in HepG2 cells.

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Section: Discussionmentioning

confidence: 99%

Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) extract induces apoptosis in human hepatocellular carcinoma HepG2 cells through caspase-dependent pathways

2014

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“…We have previously identified several bioactive xanthones from the stems of Cratoxylum formosum ssp. Pruniflorum (34, 35). We report here that CF31, one of the xanthones that we isolated, acts as a potent negative regulator of the tRXRα-mediated PI3K/AKT survival signaling pathway by binding to RXRα, thus identifying CF31 as a new lead for a class of anti-cancer agents targeting this newly identified cancer survival pathway.…”

Section: Discussionmentioning

confidence: 99%

“…We previously purified a series of xanthones from a medicinal plant, Cratoxylum formosum ssp. pruniflorum , which belongs to the Clusiaceae family and is widely distributed in several Southeast Asian countries (34, 35). Here, we report our identification of one of the xanthones, CF31, which suppresses tRXRα-dependent AKT activation through its unique RXRα binding.…”

Section: Introductionmentioning

confidence: 99%

Targeting Truncated Retinoid X Receptor-α by CF31 Induces TNF-α–Dependent Apoptosis

et al. 2013

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A truncated version of retinoid X receptor-α, tRXRα, promotes cancer cell survival by activating the PI3K/AKT pathway. However, targeting the tRXRα-mediated survival pathway for cancer treatment remains to be explored. We report here our identification of a new natural product molecule, CF31, a xanthone isolated from Cratoxylum formosum ssp. Pruniflorum, and the biological evaluation of its regulation of the tRXRα-mediated PI3K/AKT pathway. CF31 binds RXRα and its binding results in inhibition of RXRα transactivation. Through RXRα mutational analysis and computational studies, we show that Arg316 of RXRα, known to form salt bridges with certain RXRα ligands such as 9-cis-retinoic acid (9-cis-RA), is not required for the antagonist effect of CF31, demonstrating a distinct binding mode. Evaluation of several CF31 analogs suggests that the antagonist effect is mainly attributed to an interference with Leu451 of helix H12 in RXRα. CF31 is a potent inhibitor of AKT activation in various cancer cell lines. When combined with TNFα, it suppresses TNFα activation of AKT by inhibiting TNFα-induced tRXRα interaction with the p85α regulatory subunit of PI3K. CF31 inhibition of TNFα activation of AKT also results in TNFα-dependent activation of caspase-8 and apoptosis. Together, our results demonstrate that CF31 is an effective converter of TNFα signaling from survival to death by targeting tRXRα in a unique mode and suggest that identification of a natural product that targets an RXR-mediated cell survival pathway that regulates PI3K/Akt may offer a new therapeutic strategy to kill cancer cells.

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“…Benzophenone glycosides constitute an important class of biomolecules, which exist in some traditional medicinal plants 6–14. They posses important biological activities such as inhibition activity against polymorphonuclear neutrophil (PMN) respiratory burst stimulated by PMA 15, retinoid X receptor α (RXRα) transcriptional activities 16, inhibitory effect on triglyceride accumulation 17, inhibitory activities against histamine release from rat peritoneal mast cells, nitric oxide production from a murine macrophage‐like cell line (RAW 264.7) 18, inhibition against α‐glucosidase 19, and secretion of NO in mouse peritoneal macrophages 20. The plant, Aquilaria sinensis (Lour.)…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Benzophenone O‐Glycosides as α‐Glucosidase Inhibitors

Liu

Guo

et al. 2012

Archiv der Pharmazie

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The first total synthesis of benzophenone O-glycosides (iriflophenone 2-O-α-L-rhamnopyranoside: 1 and aquilarisinin: 2) isolated from the leaves of Aquilaria sinensis and related new derivatives (3-12) was accomplished through suitable protecting group manipulations and glycosylation starting from commercially available L-rhamnose, D-glucose, D-galactose, D-mannose, D-xylose, and 1,3,5-trihydroxybenzene. All synthesized benzophenone O-glycosides were evaluated for their inhibitory activities against α-glucosidase. Of these, benzophenone O-glycosides 4 and 10 exhibited the most potent inhibitory activity in vitro against α-glucosidase with IC(50) values of 168.7 ± 13.9 and 210.1 ± 23.9 µM, respectively, when compared with that of the positive control acarbose with an IC(50) value of 569.3 ± 49.7 µM.

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Xanthone and Benzophenone Glycosides from the Stems of Cratoxylum formosum ssp. pruniflorum

Cited by 22 publications

References 22 publications

Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) extract induces apoptosis in human hepatocellular carcinoma HepG2 cells through caspase-dependent pathways

Cratoxylum formosum (Jack) Dyer ssp. pruniflorum (Kurz) Gogel. (Hóng yá mù) extract induces apoptosis in human hepatocellular carcinoma HepG2 cells through caspase-dependent pathways

Targeting Truncated Retinoid X Receptor-α by CF31 Induces TNF-α–Dependent Apoptosis

Synthesis and Evaluation of Benzophenone O‐Glycosides as α‐Glucosidase Inhibitors

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