Antitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines are Mediated via Caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathway
Authors: Weimin He
Jun Chen
Changhong Zeng
Bo Guo
Journal: Pharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Anthroquinone; Apoptosis; Chrysophanol; Meningioma.
Affiliations: Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China, ., Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

Abstract:  Background: Anthroquinones are considered remarkable anticancer agents. Chrysophanol is an important anthroquinone and it has shown to have the potential to inhibit the growth of the range of cancers. However, there are no studies regarding the anticancer effects of chrysophanol against the malignant meningioma of optic nerve. In this review, the potential of chrysophanol in the treatment of malignant -meningioma of optic nerve was explored by evaluating its anticancer activity against the malignant meningioma CH157-MN cells. Materials and methods: The 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay was used for cell viability determination. The 4',6-diamidino-2-phenylindole (DAPI), acridine orange and ethidium bromide (AO/EB) and annexin V/PI assays were used to determine the induction of apoptosis. The potential of reactive oxygen species and the mitochondrial membrane was estimated by flow cytometry. Western blot analysis was performed to determine the protein expression. Results: The results showed that chrysophanol caused significant decline in the viability of the CH157-MN cells and exhibited an IC50 of 30 µmol/L. Anticancer effects were found to be due to the induction of apoptosis as evident form the DAPI and AO/EB staining. The annexin V/PI staining revealed that the apoptotic cells increased from 1.77% in control to 37.21% at 60 µmol/L concentration of chrysophanol. The Bcl-2/Bax expression ratio was decreased and the caspases-3 and 9 were activated upon chrysophanol treatment of the CH157-MN cells. Chrysophanol also triggered the formation of reactive oxygen species and reduction of the mitochondrial membrane potential in the CH157-MN cells and also blocked the Mitogen-activated protein kinase signaling pathway. Conclusion: The findings of the present study suggest that chrysophanol may prove beneficial in the treatment of malignant meningioma of optic nerve. Key Message: The study revealed the anticancer potential of chrysophanol against the malignant optic nerve meningioma. 

Retracted: Yes

PubPeer comments:
 Fig. 4.  Annexin V PI staining showing apoptotic CH157-MN cell percentage at indicated concentrations of chrysophanol. ![file] For comparison: *[left]* Fig 5B from [Bi et al (2018)] .  Effect of indicated doses of genistein on apoptosis (A) DAPI staining (B) Estimation of apoptotic Mia-PaCa2 cell populations a indicated doses by annexin V PI using flow cytometry . *[right]* Figure 6 from [Zhang et al (2018)] .  Annexin V PI showing apoptotic cell populations. .. The Figure shows that safranal triggered apoptosis at IC50 (20u03bcu039c). ![] , 
 #1 Another sighting! *[left]* Fig 4. *[right]* Figure 1B from [Zhang et al (2018)] .  Metformin induces apoptosis in ovarian cancer cells. ... (B) Apoptosis assay for OVCAR-3 cells treated with metformin as determined by Annexin V PI double staining. ![file] , 
 *[left]* Fig. 2 from [Zeng et al (2019)] .  DAPI staining showing the induction of apoptosis in the CH157-MN cells at indicated concentrations of chrysophanol. *[right]* Figure 2 from [Zhang et al (2020)] .  DAPI staining of treated CAPAN-2 pancreatic cancer cells showing membrane blebbing and formation of apoptotic crops with the mentioned doses. ![file] Mysterious overlaps are mysterious. , 
 *[left]* Fig. 2 from [Zeng et al (2019)] .  DAPI staining showing the induction of apoptosis in the CH157-MN cells at indicated concentrations of chrysophanol. *[right]* Figure 3 from [Shi et al (2019)] .  Bergenin induces apoptosis in HeLa cervical cancer cells at indicated concentrations. ![file] , 
 Fig. 3.  AO EB staining showing the induction of apoptosis in the CH157-MN cells at indicated concentrations of chrysophanol. 30 u03bcmol L 60 u03bcmol L panels. Below: contrast, lightness-enhanced versions. ![file] That s not good. , 
 2021 retraction. https: www.karger.com Article FullText 515995 The article entitled u201cAntitumor Effects of Chrysophanol in Malignant Optic Nerve Meningioma Cell Lines Mediated via caspase Activation, Induction of Mitochondrial Mediated Apoptosis, Mitochondrial Membrane Depolarization and Targeting the Mitogen-Activated Protein Kinase Signaling Pathwayu201d [Pharmacology. 2019;104:28u201335. DOI: 10.1159 000499336] by Changhong Zeng, Bo Guo, Jun Chen and Weimin He has been retracted by the Publisher and the Editor on behalf of the authors. Following publication, it was brought to the authorsu2019 attention that images presented in Figures 2 and 4 of this article had been presented in other publications. Part of the experiments in the article were performed by a third-party company, and when the authors subsequently attempted, and were unable, to reproduce the results in the article, they requested the retraction of this article. ,