Apoptosis effects of Xrel3 c-Rel/Nuclear Factor-kappa B homolog in human cervical cancer cells

Abstract

Cervical cancer is considered a common yet preventable cause of death in women. In this report, we studied the role of the NF-kappaB gene family in HeLa human cervical cancer cells, using the Xrel3 c-Rel homologue of Xenopus laevis. The expression of Xrel3/c-Rel slowed cell growth 6-fold, consistent with an upregulated expression of the cell cycle inhibitor p21. The activated PARP apoptosis effector was significantly increased (P<0.01). Based on cell viability assays Xrel3 provided an anti-apoptotic effect in 1 microM cisplatin, and this was associated with significantly lower levels of the apoptotic proteins Bax and MDM-2 (P<0.05). Furthermore, there was a 3-fold drop in the level of the tumor suppressor protein p53. In 5 microM cisplatin, expression of HeLa Xrel3 enhanced apoptosis by significantly increasing the expression of the apoptotic proteins Bax and MDM-2 (P<0.05). However, the tumor suppressor protein p53 showed a significant decrease (P<0.05) relative to the control. Thus, c-Rel/NF-kappaB may potentially be of clinical significance, especially in tumors exhibiting resistance to high-level chemotherapy.

The radiation-induced cell-death signaling pathway is activated by concurrent use of cisplatin in sequential biopsy specimens from patients with cervical cancer

“…[27][28][29] In a human cervical cancer cell line, CDKN1A and BAX expression levels change with cisplatin in a concentration-dependent manner. 30 Our results are the first clinical evidence in support of this previous research.…”

Diverse pathways mediate chemotherapy-induced cell death in acute lymphoblastic leukemia cell lines

“…We also determined if other cellular signaling pathways could modulate the apoptotic response. For example, the NFκB pathway has been implicated in apoptosis and many reports show that activation of this pathway prevents apoptosis [8,9]. Since inhibitors of this pathway are in clinical use [10,11], we focused on the role of NFκB in modulating the apoptotic response after exposure to chemotherapy.…”

Rel/Nuclear factor-kappa B apoptosis pathways in human cervical cancer cells

“…Interestingly, Xrel3 overexpression has been implicated in the development of epidermal tumors in embryos [[14] and [67]], but little is known about how these tumors form, or whether they have similar properties to human tumors. Investigating whether the Xrel3 protein had properties that could contribute to human cancer has been explored by many researchers [[68,69] and [70]]. By applying what is known about the role of Xrel3 in embryos to human cell lines, it may be possible to uncover new knowledge about the mechanism of Rel/NF-κB activity in general.…”

“…When a DNA vector encoding tagged-Xrel3 was transiently transfected into HeLa cells, Xrel3 protein constitutively localized in the nuclei, suggesting its ability to be active constantly in mammalian cells [68]. In addition, HeLa cells do not normally express Rel/NF-κB, so the transfection of Xrel3 into these cells gives the opportunity to study the activity of an interesting Rel/NF-κB protein in a negative background [[69] and [70]]. Therefore, even though Xrel3 is not a mammalian gene, its homology to the mammalian Rel/NF-κB family indicates that it may serve as a good model for gene regulation by this family enabling us to understand the mechanism of action of the Rel/NF-κB family of transcriptional regulators in cancer cells.…”

“…Recent studies by Shehata et al investigated the effect of Xrel3 overexpression on the growth of HeLa cells with and without chemotherapeutic treatment [[69] and [70]]. Results showed that Rel/NF-κB might be a possible cause of chemotherapeutic resistance encountered in cervical cancer cells.…”