Recent Progress in Medicinal Investigations on Trichosanthin and other Ribosome Inactivating Proteins from the Plant Genus Trichosanthes

Abstract

Ribosome inactivating proteins (RIPs) are toxic RNA N-glycosidases that cleave an adenine-ribose glycosidic bond at position adenine(4324) with the conserved ricin/α-sarcin loop in the eukaryotic 28S ribosomal RNA. RIPs have captured the attention of botanists, biochemists, and drug discoverers, due to their diverse potent defensive activities, and inter alia, their antitumor and anti-HIV activities. Out of the 145 families of plants, Trichosanthes ranks among the top 5 genera with a good potential of use for discovery of anticancer drugs. Trichosanthin (TCS) is a famous type I RIP purified from T. kirilowii that has been known for around 30 years. Based on the results of voluminous in vitro and in vivo investigations, TCS is considered a good candidate for the treatment of HIV/AIDS and neoplasms. Here we integrate recent progress of the research on the different medicinal activities of TCS. In addition to TCS, other promising RIPs from the same species (such as TAP29 and trichoanguin), and from the same genus Trichosanthes are included. This review presents a brief panorama of the studies on Trichosanthes RIPs. Regarding the debilitating nature of AIDS and different tumors, further understanding of these multifunctional proteins is worthwhile since it may help to open a novel therapeutic window for these stubborn diseases.

A Novel Method for Simultaneous Production of Two Ribosome-Inactivating Proteins, α-MMC and MAP30, from Momordica charantia L

“…Ribosome-inactivating proteins (RIPs) were firstly discovered in plant following the research towards to ricin [1]. In recent years, researchers commonly categorized RIPs into three types, referred to as type I, type II and type III [2].…”

MAP30 promotes apoptosis of U251 and U87 cells by suppressing the LGR5 and Wnt/β-catenin signaling pathway, and enhancing Smac expression

“…Therefore, development of novel and effective therapeutic agents is highly desirable. Although previous studies have identified that MAP30 possesses antitumor effects in various tumor cells, including glioblastoma cells, the underlying molecular mechanism of MAP30 on glioblastoma cells has not yet been elucidated (4,6,(12)(13)(14)16,21,22). The results of the present study demonstrated that MAP30 displayed significant inhibition of proliferation, invasion and migration on U87 and U251 cell lines in a dose-and time-dependent manner.…”

“…The apoptosis-promoting and cell cycle-arresting abilities of MAP30 were identified in previous studies (14,(28)(29)(30). MAP30 was considered to cleave adenine-ribose glycosidic bonds by targeting the conserved host protein synthesis machinery, and prevent the elongation of DNA/RNA, resulting in DNA replication arrest in S-phase (3,16,17).…”

“…The antitumor ability of MAP30 has been the subject of previous studies (11)(12)(13)(14)(15). However, certain researchers have already noted the effects of MAP30 on the inhibition of U87 cells in screening for anticancer effects (3,7,16,17). However, the mechanism of MAP30 on glioma cells has not been elucidated in detail.…”

Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential

“…TCS contains 12.2% α-helices, 16.3%, β-sheets, 51.4% turns, and 20.1% random curls. TCS is a type I ribosome-inactivating protein, which inactivated ribosomes by site-specific cleavage of the single N–C glycosidic bond and prevented the elongation factor from binding to the 60S ribosomal subunit, resulting in arrest of protein synthesis [102]. The mature protein is homologous to other ribosome-inactivating proteins (RIPs).…”