Chemoprevention of rat mammary carcinogenesis by spirulina
Authors: Mohammed F Ismail
Allal Ouhtit
Somya Shanmuganathan
Hamad Al-Riyami
Madhwa H G Raj
Yahya M Al-Farsi
Ishita Gupta
Rajiv L Gaur
Attalla F El-Kott
Amira Othman
Sherif H Abdeen
Augusta Fernando
Mohamed E Abdraboh
Yahia A Azab
Journal: American Journal Of Pathology (2014)
Discipline: CLINICAL MEDICINE
Keywords: Spirulina; chemopreventive effect; breast carcinogenesis; DMBA; rat
Affiliations: Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman. Electronic address: ., Department of Zoology, Faculty of Science, Mansoura University, Mansoura, Egypt., Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman., Department of Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman., Department of Botany, Faculty of Science, Mansoura University, Mansoura, Egypt., Department of Obstetrics and Gynecology, Stanley S. Scott Cancer; Louisiana State University Health Science Center, New Orleans, Louisiana.

Abstract:  Spirulina (SP) (Arthrospira platensis; previously Spirulina platensis) is a filamentous blue-green microalga (cyanobacterium) with potent dietary phytoantioxidant and anticancerous properties. We investigated the chemopreventive effect of SP against 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat breast carcinogenesis, and further studied its underlying mechanisms of action in vitro. Remarkably, SP cleared DMBA-induced rat mammary tumors, which was clearly confirmed by morphological and histological methods. SP supplementation reduced the incidence of breast tumors from 87% to 13%. At the molecular level, immunohistochemical analysis revealed that SP supplementation reduced expression of both Ki-67 and estrogen α. More interestingly, molecular analysis in the in vitro experiments indicated that SP treatment inhibited cell proliferation by 24 hours, which was accompanied by increased p53 expression, followed by increased expression of its downstream target gene, Cdkn1a (alias p21 or p21(Waf1/Cip1)). In addition, SP increased Bax and decreased Bcl-2 expression, indicating induction of apoptosis by 48 hours after SP treatment. To our knowledge, this is the first report of in vivo chemopreventive effect of SP against DMBA-induced breast carcinogenesis in rat, supporting its potential use in chemoprevention of cancer. 

Retracted: No

PubPeer comments:
 This article has an Erratum that corrects an affiliation. However, I am concerned about the animal ethics in this paper. Mammary tumors were induced by injecting female rats with DMBA. Animals were monitored for 12 months and then killed for tumor collection. Figure 2 shows mammary gland tumors in several of these rats,. Some of these tumors look very large, and must have caused animal suffering. The legend describes  ulcerated skin where the tumor breaks open, followed by a healing process . This wording and the photos suggest that animals were not sacrificed if they started to suffer, but rather had to complete the full 12m experiment. Confusingly, Figure 3 appears to show that most animals in the tumor-induction group had died at 15 weeks (5 months). How does that match the statement that the animals were sacrificed at 12 months? I could not find any statement about animal ethics approval. Could the authors please comment on the size of the tumors and the human treatment of these animals? ![file] ,