Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat

Funahashi, Hiroomi; Imai, Tsuneo; Tanaka, Yuji; Tobinaga, Junichi; Wada, Masaki; Morita, Takako; Yamada, Fumio; Tsukamura, Kyosuke; Oiwa, Mikinao; Kikumori, Toyone; Narita, Tetsuharu; Takagi, Hiroshi

doi:10.1002/(sici)1096-9098(199603)61:3<209::aid-jso9>3.0.co;2-f

Cited by 55 publications

(41 citation statements)

References 9 publications

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“…In animal models, consumption of a molecular iodine (I 2 ) diet has been demonstrated to prevent N-methyl-N-nitrosourea and dimethylbenz(a)anthracene induction of breast tumours (1,2) and to reduce breast hyperplasia and perilobular/ductal fibrosis (3). Similarly, clinical trials have revealed that I 2 has beneficial effects in fibrocystic breast disease (4) and in cyclic mastalgia (5), suggesting that iodine therapy may diminish breast disease, including breast cancer progression (6,7).…”

Section: Introductionsupporting

confidence: 57%

Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines

et al. 2016

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Abstract. Clinical trials have revealed that molecular iodine (I 2 ) has beneficial effects in fibrocystic breast disease and in cyclic mastalgia. Likewise, povidone-iodine (PVP-I), which is widely used in clinical practice as an antiseptic agent following tumour surgery, has been demonstrated to have cytotoxic effects on colon cancer and ascites tumour cells. Our previous study indicated that the growth of breast cancer and seven other human malignant cell lines was variably diminished by I 2 and iodolactones. With the intention of developing an iodine-based anticancer therapy, the present investigations extended these studies by comparing the cytotoxic capacities of I 2 , potassium iodide (KJ), PVP-I and Lugol's solution on various human carcinoma cell lines. Upon staining the cell nuclei with Hoechst 33342, the cell densities were determined microscopically. While KJ alone did not affect cell proliferation, it enhanced the antiproliferative activity of I 2 . In addition, PVP-I significantly inhibited the proliferation of human MCF-7 breast carcinoma, IPC melanoma, and A549 and H1299 lung carcinoma cells in a concentration corresponding to 20 µM I 2 . Likewise, Lugol's solution in concentrations corresponding to 20-80 µM I 2 were observed to reduce the growth of MCF-7 cells. Experiments with fresh human blood samples revealed that the antiproliferative activity of PVP-I and I 2 is preserved in blood plasma to a high degree. These findings suggest that PVP-I, Lugol's solution, and a combination of iodide and I 2 may be potent agents for use in the development of antitumour strategies.

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Section: Introductionsupporting

confidence: 57%

Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines

et al. 2016

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“…We propose a detailed mechanism of the molecular iodine (I 2 )-induced apoptosis in human breast cancer cells that may explain iodine-induced breast cancer regression in experimental rat models as well as beneficial effects observed in human fibrocystic breast subjects (3)(4)(5)(6). Iodine showed cytotoxic effects in the cultured human breast cancer cells and, in flow cytometry analysis using PI staining, confirmed apoptosis as a cell death mechanism in all of the cell lines tested, except in , and 48 h and whole cell lysate were prepared.…”

Section: Discussionmentioning

confidence: 99%

“…The beneficial effect of molecular iodine has also been documented in the human fibrocystic breast condition and in cyclic mastalgia (3,4). Iodine, in conjunction with medroxy progesterone acetate (5), and an iodine-rich seaweed "wakame" diet (6) are shown to regress 7,12-dimethylbenz(a)anthracene-induced rat breast tumors, and this effect has been corroborated by high tumor tissue iodine content (5,6) and induction of apoptosis at the tumor site (6). Iodide excess is known to induce apoptosis in the thyroid cells in vitro (7) and also in sodium iodide symporter and thyroperoxidase stably transfected non-small cell lung carcinoma cells (8).…”

mentioning

confidence: 99%

Molecular Iodine Induces Caspase-independent Apoptosis in Human Breast Carcinoma Cells Involving the Mitochondria-mediated Pathway

Shrivastava

Tiwari

Sinha

et al. 2006

Journal of Biological Chemistry

122

104

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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 iodineinduced cell death. These results demonstrate that iodine treatment activates a caspase-independent and mitochondria-mediated apoptotic pathway.

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“…We have been studying the relationship between iodine and breast cancer for 10 years, trying to determine whether iodine is useful for chemoprevention of breast cancer. [6][7][8] There have been several reports on the relationship of iodine and breast cancer, [9][10][11] but the present paper is the first concerning breast cancer chemoprevention by seaweed.…”

mentioning

confidence: 99%

Seaweed Prevents Breast Cancer?

Funahashi

Imai

Mase

et al. 2001

Japanese Journal of Cancer Research

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130

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To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4°C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.

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Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat

Cited by 55 publications

References 9 publications

Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines

Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol's solution in different human carcinoma cell lines

Molecular Iodine Induces Caspase-independent Apoptosis in Human Breast Carcinoma Cells Involving the Mitochondria-mediated Pathway

Seaweed Prevents Breast Cancer?

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