Targeting inhibitors of apoptosis in oral squamous cell carcinoma in vitro

Scheurer, Mario J.J.; Seher, Axel; Steinacker, Valentin; Linz, Christian; Hartmann, Stefan; Kübler, Alexander C.; Müller‐Richter, Urs; Brands, Roman C.

doi:10.1016/j.jcms.2019.07.022

Cited by 12 publications

(5 citation statements)

References 51 publications

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“…However, most cancer cell lines tested were resistant to the treatment of Smac mimetic [113,134,135]. To overcome the resistance of these cancers to anti-tumorigenic drugs, combination therapies with other anticancer drugs are being explored [136][137][138]. Some studies have reported accelerated disease growth after treatment with the monovalent Smac mimetic LCL161 in a lymphoma mouse model, and a cytokine release syndrome that showed an increased TNFα levels in patients treated with LCL161 [139,140].…”

Section: Targeting Xiap For Cancer Therapy; Developing Smac and Arts mentioning

confidence: 99%

Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC

Abbas

Larisch

2020

Cells

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Inhibitors of apoptosis (IAPs) are a family of proteins that regulate cell death and inflammation. XIAP (X-linked IAP) is the only family member that suppresses apoptosis by directly binding to and inhibiting caspases. On the other hand, cIAPs suppress the activation of the extrinsic apoptotic pathway by preventing the formation of pro-apoptotic signaling complexes. IAPs are negatively regulated by IAP-antagonist proteins such as Smac/Diablo and ARTS. ARTS can promote apoptosis by binding and degrading XIAP via the ubiquitin proteasome-system (UPS). Smac can induce the degradation of cIAPs but not XIAP. Many types of cancer overexpress IAPs, thus enabling tumor cells to evade apoptosis. Therefore, IAPs, and in particular XIAP, have become attractive targets for cancer therapy. In this review, we describe the differences in the mechanisms of action between Smac and ARTS, and we summarize efforts to develop cancer therapies based on mimicking Smac and ARTS. Several Smac-mimetic small molecules are currently under evaluation in clinical trials. Initial efforts to develop ARTS-mimetics resulted in a novel class of compounds, which bind and degrade XIAP but not cIAPs. Smac-mimetics can target tumors with high levels of cIAPs, whereas ARTS-mimetics are expected to be effective for cancers with high levels of XIAP.

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Section: Targeting Xiap For Cancer Therapy; Developing Smac and Arts mentioning

confidence: 99%

Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC

Abbas

Larisch

2020

Cells

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“…Like all carcinomas, OSCC consists of transformed epithelial cells that display a strong resistance to programmed cell death (apoptosis) [79]. In this regard, it must be highlighted that the intracellular signaling pathways stimulated by F. nucleatum and P. gingivalis hamper apoptosis promoters such as p53 or Bad [40,44] in oral keratinocytes (Table 1).…”

Section: Effects Of P Gingivalis and F Nucleatum Leading To The Onset...mentioning

confidence: 99%

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

Ciani,

Libonati,

Dri

et al. 2024

IJMS

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Periodontitis is linked to the onset and progression of oral squamous cell carcinoma (OSCC), an epidemiologically frequent and clinically aggressive malignancy. In this context, Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis, two bacteria that cause periodontitis, are found in OSCC tissues as well as in oral premalignant lesions, where they exert pro-tumorigenic activities. Since the two bacteria are present also in endodontic diseases, playing a role in their pathogenesis, here we analyze the literature searching for information on the impact that endodontic infection by P. gingivalis or F. nucleatum could have on cellular and molecular events involved in oral carcinogenesis. Results from the reviewed papers indicate that infection by P. gingivalis and/or F. nucleatum triggers the production of inflammatory cytokines and growth factors in dental pulp cells or periodontal cells, affecting the survival, proliferation, invasion, and differentiation of OSCC cells. In addition, the two bacteria and the cytokines they induce halt the differentiation and stimulate the proliferation and invasion of stem cells populating the dental pulp or the periodontium. Although most of the literature confutes the possibility that bacteria-induced endodontic inflammatory diseases could impact on oral carcinogenesis, the papers we have analyzed and discussed herein recommend further investigations on this topic.

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“…Unfortunately, most cancer cell lines are resistant to SMs [ 383 , 392 , 393 ]. Therefore, combinations with other anti-cancer drugs are being explored in an effort to overcome resistance [ 394 , 395 , 396 ]. Historically, SMs were developed to target XIAP, but until recently, no potent XIAP-only inhibitors were available [ 34 , 356 ].…”

Section: Targeting the Ups For Apoptosis-induced Cancer Therapymentioning

confidence: 99%

Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System

Abbas

Larisch

2021

Cells

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Apoptosis is a cell suicide process that is essential for development, tissue homeostasis and human health. Impaired apoptosis is associated with a variety of human diseases, including neurodegenerative disorders, autoimmunity and cancer. As the levels of pro- and anti-apoptotic proteins can determine the life or death of cells, tight regulation of these proteins is critical. The ubiquitin proteasome system (UPS) is essential for maintaining protein turnover, which can either trigger or inhibit apoptosis. In this review, we will describe the E3 ligases that regulate the levels of pro- and anti-apoptotic proteins and assisting proteins that regulate the levels of these E3 ligases. We will provide examples of apoptotic cell death modulations using the UPS, determined by positive and negative feedback loop reactions. Specifically, we will review how the stability of p53, Bcl-2 family members and IAPs (Inhibitor of Apoptosis proteins) are regulated upon initiation of apoptosis. As increased levels of oncogenes and decreased levels of tumor suppressor proteins can promote tumorigenesis, targeting these pathways offers opportunities to develop novel anti-cancer therapies, which act by recruiting the UPS for the effective and selective killing of cancer cells.

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Targeting inhibitors of apoptosis in oral squamous cell carcinoma in vitro

Cited by 12 publications

References 51 publications

Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC

Targeting XIAP for Promoting Cancer Cell Death—The Story of ARTS and SMAC

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System

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