Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway
Authors: Rohit A Sinha
Meenakshi Tiwari
Kalyan Mitra
Ashwani Tandon
Ashok Kumar
Ashutosh Shrivastava
Ramesh Sharma
Madan M Godbole
Anil K Balapure
Virendra K Bajpai
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Molecular iodine; breast cancer; apoptosis; cell lines; mitochondria
Affiliations: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014, India.

Abstract:  Molecular iodine (I2) is known to inhibit the induction and promotion of N-methyl-n-nitrosourea-induced mammary carcinogenesis, to regress 7,12-dimethylbenz(a)anthracene-induced breast tumors in rat, and has also been shown to have beneficial effects in fibrocystic human breast disease. Cytotoxicity of iodine on cultured human breast cancer cell lines, namely MCF-7, MDA-MB-231, MDA-MB-453, ZR-75-1, and T-47D, is reported in this communication. Iodine induced apoptosis in all of the cell lines tested, except MDA-MB-231, shown by sub-G1 peak analysis using flow cytometry. Iodine inhibited proliferation of normal human peripheral blood mononuclear cells; however, it did not induce apoptosis in these cells. The iodine-induced apoptotic mechanism was studied in MCF-7 cells. DNA fragmentation analysis confirmed internucleosomal DNA degradation. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling established that iodine induced apoptosis in a time- and dose-dependent manner in MCF-7 cells. Iodine-induced apoptosis was independent of caspases. Iodine dissipated mitochondrial membrane potential, exhibited antioxidant activity, and caused depletion in total cellular thiol content. Western blot results showed a decrease in Bcl-2 and up-regulation of Bax. Immunofluorescence studies confirmed the activation and mitochondrial membrane localization of Bax. Ectopic Bcl-2 overexpression did not rescue iodine-induced cell death. Iodine treatment induces the translocation of apoptosis-inducing factor from mitochondria to the nucleus, and treatment of N-acetyl-L-cysteine prior to iodine exposure restored basal thiol content, ROS levels, and completely inhibited nuclear translocation of apoptosis-inducing factor and subsequently cell death, indicating that thiol depletion may play an important role in iodine-induced cell death. These results demonstrate that iodine treatment activates a caspase-independent and mitochondria-mediated apoptotic pathway. 

Retracted: No

PubPeer comments:
 The images of flow cytometry in Figure 2A in red boxes look very similar with different proportion. Also those in green boxes. Please check! ![file] , 
 The high resolution image can be downloaded from the journal website. Careful examination of this figure reveals that the highlighted images in figure 2A in red boxes and green boxes are not identical. , 
 #1 Dear Sir, I am not sure that I understand the comments. This work was done 15 years back. I have since then retired in 2015. The best I can do is to bring your comments to the notice of the first author who has carried out the work and elicit his response. Once I hear from him, I will pass on the information to you , 
 #2 I do recognize the concern of #1. Below a comparison of the MDA MB 231, column 2 and 4. The numbers suggest that the M1 area in the 2nd panel is about twice as large as under the first panel. The figures are, however, identical [ click to animate ] ![file] #3 The issue is that several panels are identical. ,