Cucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells

Abstract

Nasopharyngeal carcinoma (NPC) is an Asian-prevalent head and neck cancer with high invasiveness. Although several important risk factors for NPC development have been identified, there is currently no preventive strategy for NPC, even in endemic regions. Signal transducer and activator of transcription 3 (STAT3) has been implicated in NPC carcinogenesis, which may serve as a potential target for cancer prevention. Here, we examined the chemopreventive potential of Cucurbitacin I, a natural-occurring selective inhibitor of JAK/STAT3, in NPC models. We hypothesized that Cucurbitacin I would prevent NPC invasion and tumor formation. Our data demonstrated that brief exposure of NPC cells to Cucurbitacin I was sufficient to significantly reduce the in vitro clonogenicity and in vivo tumorigenicity of NPC cells. The chemopreventive potential of Cucurbitacin I was further demonstrated by pre-dosing of the animals with Cucurbitacin I prior to tumor inoculation, which was found to be able to suppress tumor growth up to 7 days post-inoculation. The anti-proliferation activity of Cucurbitacin I was accompanied by downregulation of phospho-STAT3 and STAT3 target gene expression (e.g. cyclin D1 and Mcl-1). Cucurbitacin I also reduced the invasiveness of invasive NPC cell lines with elevated STAT3 activation. Furthermore, our data demonstrated for the first time that Cucurbitacin I harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against human cancer. Taken together, our results suggested that Cucurbitacin I may be a potent chemopreventive agent for NPC with anti-invasion and anoikis-sensitizing activities.

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

“…STAT3 may also promote cancer cell invasion and metastasis through the induction of matrix metalloprateinase-2 (MMP-2) [31] and increase angiogenesis via the induction of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α) [32] . Increasing evidence has shown that the inhibition of constitutively activated STAT3 could lead to cancer cell death and tumor regression [33][34][35] .…”

Epstein-Barr Virus LMP1 Activates EGFR, STAT3, and ERK through Effects on PKCδ

“…EGFR expression and STAT3 activation are elevated in NPC, and STAT3 activation is important for the invasiveness of EBV-associated NPC, which can be blocked by STAT3 inhibitor treatment (25,26). The effects of LMP1 on EGFR, STAT3 activation, and regulation of STAT3 target genes may be important factors in the development of NPC.…”

Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human cervical cell line is due to apoptosis and G2/M cell cycle arrest

“…Cucurbitacins normally exist as glycosides and help plants to deter predators (1). It has been reported that cucurbitacins exhibit anticancer activities against different types of cancer (2)(3)(4); however, the antitumor activity of 23,24-cucurbitacin B against cervical cancer cells remains unclear. Therefore, the present study aimed to investigate the anticancer effects of 23,24-dihydrocucurbitacin B against the human HeLa cervical cancer cell line.…”