Lippia origanoides extract induces cell cycle arrest and apoptosis and suppresses NF-κB signaling in triple-negative breast cancer cells

Raman, Vishak; Fuentes, Jorge Luı́s; Stashenko, Elena E.; Levy, Morris; Camarillo, Ignacio G.

doi:10.3892/ijo.2017.4169

Cited by 18 publications

(11 citation statements)

References 53 publications

(46 reference statements)

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“…Studies have shown that NF-κB signaling was related to apoptosis. That is to say, high activity of NF-κB signaling could cause anti-apoptosis in cancer cells [ 52 – 54 ]. Therefore, suppression of NF-κB signaling was probably responsible for Andro-induced apoptosis in MCF-7, which could also inhibit COX-2 expression.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway

Peng

Wang

Tang

et al. 2018

J Exp Clin Cancer Res

130

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BackgroundAndrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear.MethodsCell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice.ResultsThe results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo.ConclusionIn current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway

Peng

Wang

Tang

et al. 2018

J Exp Clin Cancer Res

130

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“…Although breast cancer diagnosis and therapy have both improved, satisfactory therapeutic effects have not yet been achieved due to disease complexity. Tumorigenesis is a multifactorial and multistep process involving a range of genetic alterations, including the activation of oncogenes, the inactivation of anti-oncogenes and the abnormal expression of cancer-related genes (4)(5)(6). Previous studies have unraveled some of the pathological mechanisms involved in breast tumorigenesis (7,8); however, these have yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1254 exerts�oncogenic effects by directly targeting RASSF9 in human breast cancer

Chen

Wang

et al. 2018

Int J Oncol

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MicroRNAs (miRNAs or miRs) play crucial roles in human breast cancer. Although miR-1254 has been shown to have oncogenic activity in several cancer types, its biological function in breast cancer and its mechanisms of action remain unclear. In this study, we investigated the role of miR-1254 in human breast cancer and sought to elucidate the relevant underlying mechanisms. We found that miR-1254 expression was markedly increased in breast cancer tissues and cell lines. Additionally, miR-1254 overexpression accelerated breast cancer cell proliferation, cell cycle G1-S phase transition and inhibited apoptosis. Nevertheless, the inhibition of miR-1254 suppressed cell proliferation and induced apoptosis. Further analyses revealed that miR-1254 expression negatively correlated with RASSF9 expression in breast cancer tissues. We verified that RASSF9 was a direct target of miR-1254 using a luciferase reporter assay. The overexpression of miR-1254 reduced the RASSF9 mRNA and protein levels, and the suppression of miR-1254 promoted RASSF9 expression. Notably, the knockdown or overexpression of RASSF9 corroborated the biological effects observed upon miR-1254 overexpression or inhibition. Taken together, these results demonstrate that miR-1254 accelerates breast cancer cell growth by activating the AKT signaling pathway and suppresses apoptosis by inhibiting p53 expression through the targeting of RASSF9. The data indicate that miR-1254 plays a crucial role in human breast cancer, and may represent a novel therapeutic target for this malignancy.

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“…At present, not a few DNA repair genes, such as PARP1, XRCC1, 53BP1, ERCC1, have been found to be associated with the prognosis of breast cancer [25,26]. PARP1 promotes the expression of HIF-1α by activating nuclear factor-κB (NF-κB) and promotes the polarization of macrophages M2, leading to the up-regulation of tumor-related macrophages (TAMs), such as tumor necrosis factor-α (TNFα) and IL-6, thus promoting the proliferation, invasion and metastasis of tumor cells, promoting the formation of tumor microvessels and microlymphatics [27]. And ERCC1 proteins can form heterodimers with DNA repair enzyme de ciency complementary gene (XPF) and perform functions by splicing at the 5'end of the damaged DNA single strand.…”

Section: Discussionmentioning

confidence: 99%

The Diagnostic Value of DNA Repair Gene in Breast Cancer Recurrence and Metastasis

Yang

Hao

et al. 2020

Preprint

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Background: DNA repair genes play a vital role in the treatment of many cancers, and DNA repair genes can be used in breast cancer recurrence and metastasis research. We found that the expression of DNA repair genes in breast cancer patients after recurrence and metastasis is abnormal, however, the clinical predictive significance of DNA repair genes is still elusive. Methods: The nested case-control method was used in patients with breast cancer recurrence and metastasis after surgery (n=109) and patients without recurrence and metastasis after surgery (n=109). The proteins and mRNA of DNA repair genes were detected by immunohistochemistry and Real-time PCR respectively. Results: PARP1(OR=1.485, 95%CI:1.279~1.725, P<0.05), XRCC4(OR= 1.419, 95%CI:1.217~ 1.656, P<0.05) and ERCC1 (OR=1.181, 95%CI: 1.032~1.353, P<0.05) were risk factors for postoperative recurrence and metastasis of breast cancer. Therefore, we used the ROC curve to study the optimal critical values of PARP1, XRCC4, and ERCC1, combined with the comprehensive judgment of clinical experience, we can conclude that PARP1 (cutoff value = 6, Se = 75.23%, Sp = 79.82%), XRCC4 (cutoff value = 6, Se = 78.9%0, Se = 79.82%), ERCC1 (cutoff value = 3, Se = 89.91%, Sp = 47.71%), suggesting that when the PARP1 score is higher than 6 or the XRCC4 score is higher than 6 or the ERCC1 score is higher than 3, the risk of recurrence and metastasis will increases (ORPARP1 = 14.941, 95% CIPARP1: 4.004~55.758, P <0.05; ORXRCC4 = 16.740, 95% CIXRCC4: 6.433 ~ 43.560, P <0.05; ORERCC1 = 5.285, 95% CIERCC1: 1.843 ~ 15.156, P <0.05). Due to PARP1, ERCC1 and XRCC4 belong to a part of DNA repair gene system, and the three proteins are positively correlated by correlation analysis (rPARP1-ERCC1=0.317; rPAPR1-XRCC4=0.329; rERCC1-XRCC4=0.377). The combined diagnosis of the PARR1,ERCC1 and XRCC4 have greater predictive value for the risk of recurrence and metastasis of breast cancer(Se = 88.99%, Sp = 82.57%；OR = 50.914, 95% CI: 10.918, 237.417, P <0.05).Conclusions: The recurrence and metastasis of breast cancer are predictive after PARP1>6, XRCC4>6, and ERCC1>3. The combined diagnosis of the three indicators have greater predictive value for the risk of recurrence and metastasis of breast cancer.

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Lippia origanoides extract induces cell cycle arrest and apoptosis and suppresses NF-κB signaling in triple-negative breast cancer cells

Cited by 18 publications

References 53 publications

Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway

Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway

MicroRNA-1254 exerts�oncogenic effects by directly targeting RASSF9 in human breast cancer

The Diagnostic Value of DNA Repair Gene in Breast Cancer Recurrence and Metastasis

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