Dehydrocostus lactone suppressed the proliferation, migration, and invasion of colorectal carcinoma through the downregulation of eIF4E expression

Abstract

Dehydrocostus lactone (DHC) is the main active ingredient extracted from a traditional Chinese medicine called Radix Aucklandiael. A few studies recently showed that DHC has anticancer potential. However, no reports exist as yet on the effects of DHC on colorectal carcinoma (CRC). This study aimed to determine whether and how DHC functions in CRC cells. After treatment with DHC, both Lovo and SW480 cells were significantly inhibited in their proliferation, cell cycle progression, migration, and invasion abilities in a dose-dependent and/or treatment time-dependent manner. Also, DHC significantly increased the apoptosis rate of SW480 cells, but not Lovo cells. The expression of eukaryotic translation initiation factor 4E (eIF4E), which was originally highly expressed in both cells, was significantly decreased by DHC. The inhibition of proliferation, migration, and invasion was significantly attenuated by the ectopic transfection of eIF4E, and was promoted by the knockdown of eIF4E in Lovo cells. To the best of our knowledge, this is the first time it has been shown that DHC suppressed the proliferation, cell cycle progression, antiapoptosis, and migration and invasion capabilities of CRC cells by the downregulation of eIF4E expression. In terms of the overexpression of eIF4E in many cancers, it was speculated that DHC might also play an anticancerous role by suppressing eIF4E expression. This discovery could lay the foundations for advancing our understanding of the anticancerous mechanism of DHC and developing DHC into a novel and effective natural anticancer therapeutic.

Multiple myeloma cells promote migration of bone marrow mesenchymal stem cells by altering their translation initiation

“…MAPKs are also logical and known regulators for cell translation processes [25] that may be controlled by the Ras/MNK and PI3K/Akt cascades [28]. Indeed, overexpression of eIF4E in many cancers caused elevated cell proliferation and migration, whereas eIF4E knockdown suppressed the proliferation, migration, and invasion of several cancers [18,31]. Previous studies [18,19] have also reported that eIF4E has an important role in cell migration.…”

Dehydrocostus lactone, a naturally occurring polar auxin transport inhibitor, inhibits epicotyl growth by interacting with auxin in etiolated Pisum sativum seedlings

“…AUX1 and PINs have been demonstrated to play important roles in polar auxin transport as an influx and efflux carriers, respectively [4,[11][12][13][44][45][46][47]. In etiolated pea seedlings, PsAUX1 and PsPIN1, PsPIN2 and PsPIN3 have been isolated [27][28][29][30][31][32][33][34][35][36][37][38][39]46,47]. Semiquantitative RT-PCR analysis revealed that DHCL substantially reduced accumulation of mRNA both of PsAUX1 and PsPIN1 in the etiolated pea seedlings (Fig.…”

“…A number of germacranolide-type sesquiterpene lactones with an α-methylene-γlactone derivatives obtained from natural sources have been demonstrated to exhibit pharmaceutically interesting biological activities in animals and plants. DHCL and costunolide have been demonstrated to show antitumor activity, anti-inflammatory activity, and the induction of apoptosis [26][27][28][29][30][31][32]. These compounds are also demonstrated to act as germination stimulants for the root parasitic broomrapes Orobanche cumana Wallr.…”

Dehydrocostus Lactone Enhances Chemotherapeutic Potential of Doxorubicin in Lung Cancer by Inducing Cell Death and Limiting Metastasis

“…DHC was found to induce mitochondrial intrinsic apoptosis with enhanced pro-apoptotic effects of DOX in both cell lines. DHC was shown to induce apoptosis in liver [ 9 , 10 ], breast [ 11 , 12 ], leukemia [ 13 ], prostate [ 14 ], ovary [ 15 ], colon [ 16 ], and bladder cancer [ 17 ]. DHC caused reduction in HIF-1α levels in A549 and H460 cells followed by suppression of the levels of Akt and pAkt, GSK-3β and pGSK-3β, and mTOR and p-mTOR.…”

“…DHC has been used to treat various diseases, including prevention of various types of cancers, such as liver cancer [ 9 , 10 ], breast cancer [ 11 , 12 ], leukemias [ 13 ], prostatic cancer [ 14 ], ovarian cancer [ 15 ], colorectal cancer [ 16 ], and bladder cancer [ 17 ]. DHC mediates anti-cancer effects by interacting mechanisms like inhibition of telomerase activity, induction of cellular apoptosis pathways (mitochondrial intrinsic and death-receptor dependent extrinsic), induced endoplasmic reticulum (ER) stress [ 18 ], and limiting migration-invasion and metastasis [ 8 , 16 , 19 ]. DHC prevents growth of various types of cancer by specific mechanisms like tumor necrosis factor (TNF)-α-induced degradation and phosphorylation of IkBa [ 20 ], inhibition of signal transducers, and activators of transcription 3 (STAT3) [ 9 ].…”