The natural terthiophene α-terthienylmethanol induces S phase cell cycle arrest of human ovarian cancer cells via the generation of ROS stress

Preya, Umma Hafsa; Lee, Kyung‐Tae; Kim, Nam‐Jung; Lee, Jung‐Yun; Jang, Dae Sik; Choi, Jung‐Hye

doi:10.1016/j.cbi.2017.05.011

Cited by 30 publications

(18 citation statements)

References 40 publications

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“…This cycle of mitochondrial dysfunction, ER stress, and increasing ROS levels, ultimately results in apoptosis. Similar to our findings, numerous ROS‐inducing natural compounds have been developed to target a variety of cancers, which are also shown to induce S‐phase arrest due to oxidative stress and DNA damage from high levels of free radicals . These effects appear to be cancer‐specific due to existing oxidative stress.…”

Section: Discussionsupporting

confidence: 87%

The novel capsazepine analog, CIDD‐99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1‐independent induction of ER stress, mitochondrial dysfunction, and apoptosis

Chapa

Singha

Self

et al. 2019

J Oral Pathology Medicine

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Background Oral squamous cell carcinoma (OSCC) is a deadly disease with a mere 40% five‐year survival rate for patients with advanced disease. Previously, we discovered that capsazepine (CPZ), a transient receptor potential channel, Vanilloid subtype 1 (TRPV1) antagonist, has significant anti‐tumor effects against OSCC via a unique mechanism‐of‐action that is independent of TRPV1. Thus, we developed novel CPZ analogs with more potent anti‐proliferative effects (CIDD‐24, CIDD‐99, and CIDD‐111). Methods Using OSCC xenograft models, we determined the efficacy of these analogs in vivo. TRPV1 interactions were evaluated using calcium imaging and a rat model of orofacial pain. Anti‐cancer mechanism(s)‐of‐action were assessed by cell cycle analysis and mitochondrial depolarization assays. Results CIDD‐99 was the most potent analog demonstrating significant anti‐tumor effects in vivo (P < 0.001). CIDD‐24 was equipotent to the parent compound CPZ, but less potent than CIDD‐99. CIDD‐111 was the least efficacious analog. Calcium imaging studies confirmed that CIDD‐99 neither activates nor inhibits TRPV1 confirming that TRPV1 activity is not involved in its anti‐cancer effects. All analogs induced an S‐phase block, dose‐dependent mitochondrial depolarization, and apoptosis. Histological analyses revealed increased apoptosis and reduced cell proliferation in tumors treated with these analogs. Importantly, CIDD‐99 had the most dramatic anti‐tumor effects with 85% of tumors resolving leaving only minute traces of viable tissue. Additionally, CIDD‐99 was non‐noxious and demonstrated no observable adverse reactions Conclusion This study describes a novel, highly efficacious, CPZ analog, CIDD‐99, with dramatic anti‐tumor effects against OSCC that may be efficacious as a lone therapy or in combination with standard therapies.

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Section: Discussionsupporting

confidence: 87%

The novel capsazepine analog, CIDD‐99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1‐independent induction of ER stress, mitochondrial dysfunction, and apoptosis

Chapa

Singha

Self

et al. 2019

J Oral Pathology Medicine

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“…Passing these checkpoints, the cell will proceed with division. External factors such as drugs (5-fluorouracil), radiation, and reactive oxygen species result in DNA-damage-related cell death during S phase [42, 43]. The abnormality of DNA prevents the progress of replication and influences the next new one.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, cytotoxicity and antitumour mechanism investigations of polyoxometalate doped silica nanospheres on breast cancer MCF-7 cells

Cao

et al. 2017

PLoS ONE

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Polyoxometalates (POMs) have shown the potential anti-bacterial, anti-viral and anti-tumor activities. In order to improve their physiological stability and antitumour activity for medical application, K2Na[AsIIIMo6O21(O2CCH2NH3)3]·6H2O doped silica nanospheres (POM@SiO2) with diameters of ~40 nm have been synthesized by the water-in-oil microemulsion method in this study. The obtained spheres were morphologically uniform nanosized and nearly monodispersed in solution. The nanoparticles had high entrapment efficiency, which was upto 46.2% by the inductively coupled plasma mass spectrometry (ICP-MS) analysis and POMs slowly released from the nanospheres both in the PH 7.4 and 5.5 phosphate buffer saline (PBS) solutions in 60 h. The in vitro MTT assays of particles on MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to that of plain polyoxometalate. The IC50 value of the POM@SiO2 nanoparticles was 40.0 μg/mL at 24 h calculated by the encapsulated POM concentration, which was much lower comparing to that of 2.0 × 104 μg/mL according to the pure POM. And the SiO2 shells showed low inhibitory effect at the corresponding concentration. Confocal images further indicated the cell morphology changes and necrosis. Flow cytometric analysis showed nanoparticles induced the apoptosis by arresting the cells in S phase and western blot analysis indicated they promoted apoptosis by inhibiting the Bcl-2 protein. Moreover, the study of interactions between human serum albumin (HSA) and the nanoparticles indicated the fluorescence quenching was static, and the nanoparticles were likely to bind to HSA and changed its conformation.

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“…Moreover, activation of the MAPK pathway can result in apoptosis via death signals including the c-Jun N-terminal kinase (JNK) pathway and caspase family ( 21 ). The cancer cells that continue to proliferate tend to induce DNA damage and to elicit cell cycle arrest ( 22 , 23 ). Therefore, excessive production of ROS can provoke cell cycle arrest, apoptosis, and senescence.…”

Section: Relationship Between Ros and Cancermentioning

confidence: 99%

Potential roles of reactive oxygen species derived from chemical substances involved in cancer development in the female reproductive system

2018

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Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women’s cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

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The natural terthiophene α-terthienylmethanol induces S phase cell cycle arrest of human ovarian cancer cells via the generation of ROS stress

Cited by 30 publications

References 40 publications

The novel capsazepine analog, CIDD‐99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1‐independent induction of ER stress, mitochondrial dysfunction, and apoptosis

The novel capsazepine analog, CIDD‐99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1‐independent induction of ER stress, mitochondrial dysfunction, and apoptosis

Synthesis, cytotoxicity and antitumour mechanism investigations of polyoxometalate doped silica nanospheres on breast cancer MCF-7 cells

Potential roles of reactive oxygen species derived from chemical substances involved in cancer development in the female reproductive system

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