Natural borneol, a monoterpenoid compound, potentiates selenocystine-induced apoptosis in human hepatocellular carcinoma cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage
Authors: Jianyu Su
Tianfeng Chen
Jianping Chen
Lin Li
Yum-Shing Wong
Xiaoling Li
Haoqiang Lai
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Selenocystine; Natural borneol; Anticancer activities; Cellular uptake; Antiproliferative activity
Affiliations: College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, China. 

Abstract:  Selenocystine (SeC) has been identified as a novel compound with broad-spectrum anticancer activities. Natural borneol (NB) is a monoterpenoid compound that has been used as a promoter of drug absorption. In the present study, we demonstrated that NB significantly enhanced the cellular uptake of SeC and potentiated its antiproliferative activity on HepG2 cells by induction of apoptosis. NB effectively synergized with SeC to reduce cancer cell growth through the triggering apoptotic cell death. Further mechanistic studies by Western blotting showed that treatment of the cells with NB and SeC activated the intrinsic apoptotic pathway by regulation of pro-survival and pro-apoptotic Bcl-2 family proteins. Treatment of the cells with NB and SeC induced the activation of p38MAPK and inactivation of Akt and ERK. NB also potentiated SeC to trigger intracellular ROS generation and DNA strand breaks as examined by Comet assay. Moreover, the thiol-reducing antioxidants effectively blocked the occurrence of cell apoptosis, which confirmed the important role of ROS in cell apoptosis. Taken together, these results reveal that NB strongly potentiates SeC-induced apoptosis in cancer cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage. NB could be further developed as a chemosensitizer of SeC in treatment of human cancers. 

Retracted: No

PubPeer comments:
 Figure 1D. * Blue boxes: The Co-treatment and Pre-treatment Control panels appear to look the same * Green boxes: The Co-treatment and Pre-treatment NB panels appear to show an overlap ![file] Reported to the journal in 2014, with a friendly reminder in 2016, but no action yet. , 
 Dear reader and Pubpeer, I am very sorry for delaying answering the comment. We have carefully checked all original data and contacted 4 times with the Journal editorial office for the corrections of this paper, and we have also provided three panels of origin data and the correct images to the editor. And we are now waiting for the correction by the editor office. Actually, in this study, we found that NB alone, even at the concentration of 160 u03bcg mL, induced negligible growth inhibition on HepG2 cells for 24 h. The cell morphology for pretreatment and cotreatment NB (80 u03bcg mL) alone groups showed no difference, so we intended to show that there are no differences between these two NB alone treatment groups in Figure 1D. However, the images of MTT staining for the pre-treatment control and NB groups were wrongly put by us carelessly, but this mistake did not affect the results and conclusion of this work. We have no intention to use the same images to describe different results. Therefore, to avoid the misunderstanding, we have contacted with the Journal editorial office to replace the image of MTT staining for the pre-treatment groups of u201ccontrolu201d and u201cNBu201d in Figure 1D to make it clear. Moreover, we provide all of the original images of MTT staining in the control groups and NB treatment groups. Thank you for your kind reminder. We will carefully check all original data in future, and ensure not to make any modification. Regards, The Authors Team The corrected MTT staining image of cells after treatments as examined by light microscopy in Figure 1D was attached below. ![file] ,