Abstract
2-Aminophenoxazine-3-one (Phx-3), an oxidative phenoxazine, exerts strong anticancer effects on various cancer cell lines originating from different organs, in vitro. This article reviews new aspects for the prevention of carcinogenesis and development of gastric and colon cancers by Phx-3, based on the strong anticancer effects of Phx-3 on gastric and colon cancer cell lines (direct anticancer effects of Phx-3 for preventing development of cancer), the bacteriocidal effects of Phx-3 against Helicobacter pylori associated with carcinogenesis of gastric cancer (indirect anticancer effects for preventing carcinogenesis of gastric cancer), and the proapoptotic activity of Phx-3 against human neutrophils involved in the incidence of ulcerative colitis associated with a high colon cancer risk (indirect anticancer effects for preventing carcinogenesis of colon cancer).
Highlights
Tomoda and colleagues found in 1986 [2] that Phx-3 can be produced during the reaction of human erythrocytes or hemoglobin with o-aminophenol, and later demonstrated that it does exert strong anticancer effects both on various cancer cell lines [3,4,5,6,7,8] and cancer cell-transplanted mice in vivo [9,10], as well as antimicrobial effects against Helicobacter pylori [11], Chlamydia pneumoniae [12], some mycobacterial species [13], and herpes viruses [14]
Phx-3 efficiently suppresses the activity of Akt, which is responsible for the cell survival of cancer cells [7]. These results indicate that Phx-3 has the potential to promote apoptosis of cancer cells, and may be applied to treat such cancers as gastric cancer and colon cancer, which are refractory to chemotherapy
Since we found that Phx-3 extensively prevents the growth of gastric and colon cancer cell lines in vitro [8,15,16,17], we analyzed its cytotoxic and proapoptotic activities, focusing on the anticancer mechanism for preventing the development of gastric and colon cancer
Summary
2-Aminophenoxazine-3-one (Phx-3) (Figure 1) was first reported as the antibiotics for streptomyces discovered in soil in Kunitachi, Tokyo, Japan, in 1959 [1]. Tomoda and colleagues found in 1986 [2] that Phx-3 can be produced during the reaction of human erythrocytes or hemoglobin with o-aminophenol, and later demonstrated that it does exert strong anticancer effects both on various cancer cell lines [3,4,5,6,7,8] and cancer cell-transplanted mice in vivo [9,10], as well as antimicrobial effects against Helicobacter pylori [11], Chlamydia pneumoniae [12], some mycobacterial species [13], and herpes viruses [14]. In 1992, Tabuchi et al [22] found that tumor size significantly reduced when neutrophil (=granulocyte) was deleted by extracorporeal circulation after being transplanted with VX2 carcinoma cells, a rabbit papilloma cell line Later, they demonstrated that neutrophils play a critical role in the development of colon cancer. These indirect anticancer effects of Phx-3 were analyzed in terms of preventing carcinogenesis of gastric and colon cancers
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