<i>In vitro</i>and<i>in vivo</i>anti-tumor activity of CoQ0 against melanoma cells: inhibition of metastasis and induction of cell-cycle arrest and apoptosis through modulation of Wnt/β-catenin signaling pathways

Hseu, You‐Cheng; Thiyagarajan, Varadharajan; Tsou, Hsiao-Tung; Lin, Kai-Yuan; Chen, Hui-Jye; Lin, Chung-Ming; Liao, Jiunn‐Wang; Yang, Hsin‐Ling

doi:10.18632/oncotarget.7983

Cited by 40 publications

(31 citation statements)

References 55 publications

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“…Sp1-4 factors may play a role in activating some signaling pathways and receptors and contribute to oncogenic properties of cancer cells [13]. Attenuation of Wnt/β-catenin signaling resulted in inhibition of survivin expression in several cell types, suggesting a positive regulation of survivin expression by this pathway in the tested cell lines [14,15]. Herceptin inhibited survivin expression through the ErbB2-β-catenin/TCF4 pathway in breast cancer cells, completely dependent on TCF-4 binding sites in the promoter [16].…”

Section: Positive Regulation Of Survivin Expresssionmentioning

confidence: 99%

Insights into the Regulation of Survivin Expression in Tumors

Vachtenheim¹,

Vlčková²

2016

Single Cell Biol

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Survivin, an anti-apoptotic protein was found to be expressed in tumors, whereas in normal tissues the expression of this protein was shown to be absent or extremely low. Survivin exhibits multifunctional activity in tumor cells. Survivin is the smallest member of the inhibitor of apoptosis protein family and was demonstrated to have key roles in regulating cell division and inhibiting apoptosis. The cancer protein survivin was shown to be associated with tumor cell progression, invasiveness, resistance to therapeutics and poor prognosis. Its level in tumors is associated with deregulation of several oncogenic pathways. In this review, a delineation of survivin expression and progress in understanding the survivin transcriptional regulation with the emphasis of augmented apoptosis in cancer and its link to the Hedgehog pathway and cancer stem cells is discussed.

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Section: Positive Regulation Of Survivin Expresssionmentioning

confidence: 99%

Insights into the Regulation of Survivin Expression in Tumors

Vachtenheim¹,

Vlčková²

2016

Single Cell Biol

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“…Previous studies have shown that inhibition of the Wnt/β-catenin signaling pathway attenuates survival signals and induces apoptosis (15,16). Autophagy is a highly conserved pathway that is activated under stress and plays a pivotal role in a plethora of physiological processes including cell death (17).…”

Section: Introductionmentioning

confidence: 99%

Role of Wnt/β-catenin pathway in inducing autophagy and apoptosis in multiple myeloma cells

Wang

2016

Oncology Letters

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β-catenin is the downstream effector of the Wnt signaling pathway, which regulates cell proliferation and differentiation. Activation of the Wnt/β-catenin signaling pathway has been shown to positively correlate with prognosis in several types of malignancies. The present study aimed to determine the role of β-catenin in multiple myeloma (MM) cells using lentiviruses expressing small interfering RNA (siRNA). The expression of β-catenin in the MM cell line RPMI-8826 was evaluated following β-catenin knockdown by the siRNA. Subsequently, the activation of autophagy in MM cells was assessed by transmission electron microscopy and western blot analyses. Cell apoptosis and the expression of apoptosis-related proteins following β-catenin silencing was investigated by flow cytometry and western blotting, respectively. A significant decrease in β-catenin expression was observed in the MM cell line expressing β-catenin-specific siRNA. Activation of autophagy was induced by β-catenin silencing, as evidenced by increases in the number of autophagic vacuoles and the expression of the autophagy-related proteins microtubule-associated protein 1 light chain 3 and Beclin-1. Furthermore, the expression of 5′-adenosine monophosphate-activated protein kinase was increased, and that of mechanistic target of rapamycin was decreased, following β-catenin silencing. In addition, there was an increase in the rate of apoptosis of MM cells following β-catenin silencing, accompanied by increased protein expression of phosphorylated p53, active caspase-3 and B-cell lymphoma (Bcl)-2-associated X protein, and decreased protein expression of Bcl-2. The results of the present study suggested that β-catenin silencing induced autophagy and apoptosis in MM cells. To the best of our knowledge, this is the first study to demonstrate that a β-catenin deficiency induces autophagy in MM cells. These findings suggested that inhibition of β-catenin could be a potential therapeutic target for patients with MM.

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“…Membranes were incubated with the following desired primary antibodies: matrix metalloproteinase (MMP)-9 (1: 1,000, catalog no. sc-6840, Santa Cruz Biotechnology) (7,14,31), p-AKT (1:1,000, catalog no. 4085L, Cell Signaling) (17,18,50), AKT (1:1,000, catalog no.…”

Section: Methodsmentioning

confidence: 99%

PTEN inhibitor VO-OHpic attenuates inflammatory M1 macrophages and cardiac remodeling in doxorubicin-induced cardiomyopathy

Johnson

Singla

2018

American Journal of Physiology-Heart and Circulatory Physiology

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Doxorubicin (Doxo) is an effective agent commonly used in cancer therapeutics. Unfortunately, Doxo treatment can stimulate cardiomyopathy and subsequent heart failure, limiting use of this drug. The role of phosphatase and tensin homolog (PTEN) in apoptosis has been documented in Doxo induced cardiomyopathy (DIC) and heart failure models. However, whether direct inhibition of PTEN attenuates apoptosis, cardiac remodeling, and inflammatory M1 macrophages in DIC model remains elusive. Therefore, the current study is designed to understand effects of VO-OHpic (VO), a potent inhibitor of PTEN, in reducing apoptosis and cardiac remodeling. At D56, echocardiography was performed, which shows VO-OHpic treatment significantly (p<0.05) improves heart function. Immunohistochemistry, TUNEL, and histological staining were used to determine apoptosis, pro-inflammatory M1 macrophages, anti-inflammatory M2 macrophages, and cardiac remodeling. Our data shows a significant increase in apoptosis, hypertrophy, fibrosis, and pro-inflammatory M1 macrophages with Doxo treatment, whereas VO treatment significantly reduced apoptosis, adverse cardiac remodeling, and pro-inflammatory M1 macrophages significantly (p<0.05) compared to Doxo group. Western blotting confirmed the reduction of p-PTEN and increase in p-AKT protein expression in the Doxo+VO group. Moreover, VO administration increased anti-inflammatory M2 macrophages. Collectively, our data suggests that VO-OHpic treatment attenuates apoptosis and adverse cardiac remodeling, a process that is mediated through PTEN/AKT pathway, resulting in improved heart function in DIC.

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In vitroandin vivoanti-tumor activity of CoQ0 against melanoma cells: inhibition of metastasis and induction of cell-cycle arrest and apoptosis through modulation of Wnt/β-catenin signaling pathways

Cited by 40 publications

References 55 publications

Insights into the Regulation of Survivin Expression in Tumors

Insights into the Regulation of Survivin Expression in Tumors

Role of Wnt/β-catenin pathway in inducing autophagy and apoptosis in multiple myeloma cells

PTEN inhibitor VO-OHpic attenuates inflammatory M1 macrophages and cardiac remodeling in doxorubicin-induced cardiomyopathy

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