Isothiocyanate From Moringa oleifera Seeds Inhibits the Growth and Migration of Renal Cancer Cells by Regulating the PTP1B-dependent Src/Ras/Raf/ERK Signaling Pathway

Abstract

Moringa oleifera Lam. is a tropical and subtropical plant that has been used for centuries as both food and traditional medicine. 4-[(α-L-Rhamnosyloxy) benzyl] isothiocyanate (MIC-1) is an active substance in M. oleifera, with anti-cancer activity. However, whether MIC-1 exerts anti-renal cancer effects is unknown. Therefore, the aim of the present study was to evaluate the effects of MIC-1 on the growth and migration of renal cell carcinoma (RCC) cells and to identify the putative underlying mechanism. We found that, among 30 types of cancer cells, MIC-1 exerted the strongest growth inhibitory effects against 786-O RCC cells. In addition, MIC-1 (10 μM) significantly inhibited the growth of five RCC cell lines, including 786-O, OSRC-2, 769-P, SK-NEP-1, and ACHN cells, but was not toxic to normal renal (HK2) cells. Also, MIC-1 suppressed 786-O and 769-P cell migration and invasion abilities, and reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, MIC-1 induced apoptosis and cell cycle arrest, increased Bax/Bcl-2 ratio, and decreased cell cycle-related protein expression in 786-O cells and 769-P cells. Molecular docking and small-molecule interaction analyses with PTP1B both showed that MIC-1 inhibited PTP1B activity by binding to its active site through hydrogen bonding and hydrophobic interactions. Additionally, MIC-1 could suppress the growth and migration of 786-O cells by inhibiting PTP1B-mediated activation of the Src/Ras/Raf/ERK signaling pathway. In vivo experiments further showed that MIC-1 markedly inhibited the growth of xenograft tumors in mice, and greatly increased Bax/Bcl-2 ratio in tumor tissues. In addition, MIC-1 had no effect on the PTP1B-dependent Src/Ras/Raf/ERK signaling pathway in HCT-116 cells, Hep-G2 cells, and A431 cells. Overall, our data showed that MIC-1 could be a promising, non-toxic, natural dietary supplement for the prevention and treatment of renal cancer.

A PTP1B-Cdk3 signaling axis promotes cell cycle progression of human glioblastoma cells through an Rb-E2F dependent pathway

“…The effect observed in GB cells was not unexpected, since a previous report demonstrates that in pancreatic ductal adenocarcinoma cells, PTP1B knockdown induces cell cycle arrest in G0/G1 phase with the consequent down-regulation of some cell cycle regulators needed for the G1/S transition such as CDK2, CDK4 and Cyclin D1 [41]. Furthermore, it has also been reported that PTP1B inhibition induces a G2 cell cycle arrest in renal cell carcinoma, pancreatic and hepatic cancer cells [42, 43]. However, the molecular mechanism by which PTP1B regulates cell cycle progression in these cellular models has not been explored.…”

Licochalcone A Suppresses Renal Cancer Cell Proliferation and Metastasis by Engagement of Sp1-Mediated LC3 Expression

“…RCC has been treated with phytochemicals with pharmacological effects, including antioxidant, anti-inflammatory, and antineoplastic characteristics. [ 40 , 41 ]. Kaempferol, a polyphenol belonging to the flavonoid subgroup, exerted antiproliferative and antimetastasis effects in 786-O cells by attenuating metalloproteinase-2 (MMP-2) expression through the downregulation of the Akt and FAK signaling pathways [ 26 ].…”

Multi-Target Antibacterial Mechanism of Moringin From Moringa oleifera Seeds Against Listeria monocytogenes

“…The strain was inoculated into the nutrient broth (NB) and cultured at 37°C for 18 h to the logarithmic growth phase. Moringin was obtained from Moringa seeds with reference to a previous method ( Xie et al, 2021 ).…”