Corrigendum: Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/ß-Catenin Signaling Pathway.

[This corrects the article DOI: 10.3389/fphar.2020.523962.].

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.

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.

Moringa oleifera Alkaloids Inhibited PC3 Cells Growth and Migration Through the COX-2 Mediated Wnt/ß-Catenin Signaling Pathway.

Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), ß-catenin, phosphorylated glycogen synthase 3ß, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (ß-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and ß-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/ß-catenin signaling pathway.