Anticancer Activity of Mukonal Against Human Laryngeal Cancer Cells Involves Apoptosis, Cell Cycle Arrest, and Inhibition of PI3K/AKT and MEK/ERK Signalling Pathways
Authors: Yang Liping
Lu Huizhi
Deng Xinxin
Wang Binu
Liu Li
Zhang Yingying
Wu Longjun
Journal: Medical Science Monitor (2018)
Discipline: CLINICAL MEDICINE
Keywords: Laryngeal cancer; Mukonal; Anticancer effects; Cell viability; Apoptosis
Affiliations: Department of Ear, Nose and Throat (ENT), Tongren Hospital of WuHan University (Wuhan Third Hospital), Wuhan, Hubei, China (mainland)., Department of Critical Care Medicine, Tongren Hospital of WuHan University (Wuhan Third Hospital), Wuhan, Hubei, China (mainland).

Abstract:  BACKGROUND Laryngeal cancer is one of the major malignancies of the neck and head and is responsible for considerable mortality across the globe. The treatments for laryngeal cancer mainly involve surgical interventions followed by chemotherapy. However, due to unsatisfactory results, constant relapses and the adverse effects associated with the currently used drugs, there is pressing need to develop effective drug options for treatment of laryngeal cancer. Therefore, this study was undertaken to investigate the anticancer effects of a plant-derived alkaloid, Mukonal, against human AMC-HN-8 laryngeal cancer cells. MATERIAL AND METHODS The WST-1 and clonogenic assays were employed to determine the cell viability. Apoptosis was detected by Hoechst and AO/EB staining. Cell migration and cell cycle analysis was performed by Transwell assay and flow cytometry, respectively. Protein expression was examined by Western blotting. RESULTS The results revealed that Mukonal reduced the viability of laryngeal cancer cells dose-dependently. The IC50 of Mukonal was found to be 10 µM. However, the effects of Mukonal on the normal HuLa-PC cells was found to be 140 µM. The decrease in the viability of the AMC-HN-8 laryngeal cancer cells was found to be due to the induction of apoptosis and G2/M cell cycle arrest. Mukonal also suppressed the cell migration and of the AMC-HN-8 laryngeal cancer cells. Mukonal could also inhibit the PI3K/AKT and MEK/ERK signalling pathways in a concentration-dependent manner. CONCLUSIONS Taken together, we conclude that Mukonal could prove a beneficial lead molecule for the treatment of laryngeal cancer. 

Retracted: No

PubPeer comments:
 *[middle]* Figure 4 from [Li et al (2018)] .  AO EB staining showing induction of apoptosis in AMC-HN-8 cells upon treatment with Mukonal . *[left]* Fig 1(E) from [Chen et al (2019)] .  AO EB staining for apoptosis . *[right]* Fig 2C,D from [Du et al (2020)] .  DAPI staining of miR-NC and miR-143 mimics transfected CAMA-1 cells. ...  AO EB staining of miR-NC and miR-143 mimics transfected CAMA-1 cells . ![file] , 
 *[right]* Figure 6 from [Li et al (2018)] .  Effect of Mukonal on the migration of the AMC-HN-8 cells as revealed by the Transwell assay. *[left]* Figure 7 from [Wei et al (2019)] .  Effect of Chrysoeriol on the invasion of the A549 cells as determined by Boyden chamber assay. The Figure shows that Chrysoeriol inhibited the tendency for invasion. ![file] UPDATE: Another sighting! Figure 4(D) from [Jun et al (2018)] .  Effect of MAPK1 silencing on NCI-H23 invasion . ![file] , 
 *[right]* Fig 6 again: ![file] The source of the panels turns out to be Figs 1D, 2B of  miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells ([Li et al 2014] ). ![file] , 
 Retracted [19 July 2022] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. , 
 #4 There is so much passive voice in this notice that I fell asleep before finishing. ,