Inhibition of PDGFR by CP-673451 induces apoptosis and increases cisplatin cytotoxicity in NSCLC cells via inhibiting the Nrf2-mediated defense mechanism

Yang, Yang; Deng, Yao; Chen, Xiangcui; Zhang, Jiahao; Chen, Yueming; Li, Huachao; Wu, Qinghua; Yang, Zhicheng; Zhang, Luyong; Liu, Bing

doi:10.1016/j.toxlet.2018.05.033

Cited by 14 publications

(4 citation statements)

References 32 publications

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“…Several studies demonstrated that inhibiting CAFs from expressing several markers, including FAP-a and PDGFR-b, can prevent cancer growth (Camorani et al, 2018;Kishi et al, 2018;Lin et al, 2018;Lo et al, 2015;Teichgraber et al, 2015;Truffi et al, 2018;Wang et al, 2014;Yang et al, 2018). Based on our bioinformatic analysis of the selected cancers in this study, blocking ACTA2, PDGFR-b, and FAPa might potentially influence cancer growth and can be evaluated in the future in combination with therapeutic agents as potential anticancer treatment.…”

Section: Discussionmentioning

confidence: 88%

Broadening Drug Design and Targets to Tumor Microenvironment? Cancer-Associated Fibroblast Marker Expression in Cancers and Relevance for Survival Outcomes

Dzobo

Dandara

2020

OMICS: A Journal of Integrative Biology

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Solid tumors have complex biology and structure comprising cancer cells, stromal cells, and the extracellular matrix. While most therapeutics target the cancer cells, recent data suggest that cancer cell behavior and response to treatment are markedly influenced by the tumor microenvironment (TME). In particular, the cancerassociated fibroblasts (CAFs) are the most abundant stromal cells, and play a significant contextual role in shaping tumor initiation, progression, and metastasis. CAFs have therefore emerged as part of the nextgeneration cancer drug design and discovery innovation strategy. We report here new findings on differential expression and prognostic significance of CAF markers in several cancers. We utilized two publicly available resources: The Cancer Genomic Atlas and Gene Expression Profiling Interactive Analysis. We examined the expression of CAF markers, ACTA2, S100A4, platelet-derived growth factor receptor-beta [PDGFR-b], CD10, and fibroblast activation protein-alpha (FAP-a), in tumor tissues versus the adjacent normal tissues. We found that CAF markers were differentially expressed in various different tumors such as colon, breast, and esophageal cancers and melanoma. No CAF marker is expressed in the same pattern in all cancers, however. Importantly, we report that patients with colon adenocarcinoma and esophageal carcinoma expressing high FAP-a and CD10, respectively, had significantly shorter overall survival, compared with those with low levels of these CAF markers ( p < 0.05). We call for continued research on TME biology and clinical evaluation of the CAF markers ACTA2, S100A4, PDGFR-b, CD10, and FAP-a in relation to prognosis of solid cancers in large population samples. An effective cancer drug design and discovery roadmap in the 21st century ought to be broadly framed, and include molecular targets informed by both cancer cell and TME variations.

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Section: Discussionmentioning

confidence: 88%

Broadening Drug Design and Targets to Tumor Microenvironment? Cancer-Associated Fibroblast Marker Expression in Cancers and Relevance for Survival Outcomes

Dzobo

Dandara

2020

OMICS: A Journal of Integrative Biology

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“…Neurotic and undeveloped defensive styles, in fact, distort the reality in people with death obsession thoughts, and the degree of the reality distortion in psychologically sad and undeveloped defenses is more than the developed ones. In another explanation based on the cognitive perspective, the more cognitive distortions of an event, situation, and even behavior, the less the level of conscious awareness thereupon, and consequently, less effort is made to deal with cognitive distortion [13]. Consequently, during a false period, the psychologically sad and undeveloped defensive styles increase and consequently, the obsession with the death and life phenomenons greatly increases [11].…”

Section: Discussionmentioning

confidence: 99%

“…Defenses are divided into undeveloped and developed neurotic categories [12]. The defensive undeveloped defense is considered to be regressive; while neurotic defenses are divided into obsessive and suppressive components [13]. Developed defensive mechanisms are considered to be adaptive, normal, and efficient methods of exposure [14].…”

Section: Introductionmentioning

confidence: 99%

The Relationship of Defensive Styles and Islamic Quality of Life with Death Obsession in Women with Breast Cancer

Sangani

Ramak

Azizi

et al. 2020

Multidiscip Cancer Investig

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Introduction: Breast cancer is one of the most common types of cancer in women with an increasing outbreak. The present study aimed to investigate the relationship between defensive styles and Islamic quality of life (QoL) with death obsession in women with breast cancer. Methods: This research was a correlational study. The statistical population of the study included 220 female patients with breast cancer; referring to Cancer Patients Association of Gorgan in 2019. According to Krejcie and Morgan’s table, 136 women were selected from breast cancer patients by simple random sampling. Islamic QoL questionnaire of Mohammad Namaqi et al., defense styles questionnaire of Andrews et al., and obsession with death questionnaire of Abdel-Khalek were applied. Data were analyzed; using the Kolmogorov-Smirnov test, Pearson correlation, and stepwise regression. Results: The results showed that there was a negative significant relationship betweenthe developed defensive style and the Islamic QoL with death obsession (P=0.001). There was a positive significant relationship between the neurotic and undeveloped defensive style with the death obsession (P=0.001). In addition, the results of the regression showed that the Islamic QoL (-0.257) and developed defensive style (-0.196) had the potential for predicting the obsession of death. Conclusions: These results emphasize the necessity of the role defensive styles and Islamic QoL on the death obsession. So, therapists and counseling in the treatment of cancer for reducing obsession may benefit from paying attention to Islamic QoL and defensive styles.

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“…Another recent study investigated the anticancer effects of CP-673451, a selective PDGFR β inhibitor, in models of NSCLC. Here, CP-673451 was found to suppress NRF2 expression and promote a significant increase in cell apoptosis, accompanied by ROS accumulation in A549 and H358 NSCLC cell lines that was further exacerbated by the coadministration of Cisplatin [334]. Taken together, these data support the concept that NRF2 is a crucial determinant of therapy resistance against TKRIs in lung and breast cancers and further highlight the importance of combinatorial regimens wherein NRF2 inhibition might represent the prerequisite to restore or at least improve the efficacy of already established drugs and achieve optimal therapeutic effects.…”

Section: Therapeutic Strategies For Nrf2 Inhibition In Cancermentioning

confidence: 99%

Potential Applications of NRF2 Inhibitors in Cancer Therapy

Panieri¹,

Saso²

2019

Oxidative Medicine and Cellular Longevity

150

128

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The NRF2/KEAP1 pathway represents one of the most important cell defense mechanisms against exogenous or endogenous stressors. Indeed, by increasing the expression of several cytoprotective genes, the transcription factor NRF2 can shelter cells and tissues from multiple sources of damage including xenobiotic, electrophilic, metabolic, and oxidative stress. Importantly, the aberrant activation or accumulation of NRF2, a common event in many tumors, confers a selective advantage to cancer cells and is associated to malignant progression, therapy resistance, and poor prognosis. Hence, in the last years, NRF2 has emerged as a promising target in cancer treatment and many efforts have been made to identify therapeutic strategies aimed at disrupting its prooncogenic role. By summarizing the results from past and recent studies, in this review, we provide an overview concerning the NRF2/KEAP1 pathway, its biological impact in solid and hematologic malignancies, and the molecular mechanisms causing NRF2 hyperactivation in cancer cells. Finally, we also describe some of the most promising therapeutic approaches that have been successfully employed to counteract NRF2 activity in tumors, with a particular emphasis on the development of natural compounds and the adoption of drug repurposing strategies.

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Inhibition of PDGFR by CP-673451 induces apoptosis and increases cisplatin cytotoxicity in NSCLC cells via inhibiting the Nrf2-mediated defense mechanism

Cited by 14 publications

References 32 publications

Broadening Drug Design and Targets to Tumor Microenvironment? Cancer-Associated Fibroblast Marker Expression in Cancers and Relevance for Survival Outcomes

Broadening Drug Design and Targets to Tumor Microenvironment? Cancer-Associated Fibroblast Marker Expression in Cancers and Relevance for Survival Outcomes

The Relationship of Defensive Styles and Islamic Quality of Life with Death Obsession in Women with Breast Cancer

Potential Applications of NRF2 Inhibitors in Cancer Therapy

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