The neddylation inhibitor <scp>MLN4924</scp> inhibits proliferation and triggers apoptosis of oral cancer cells but not for normal cells

Chen, Yan‐Ning; Chan, Yu‐Hsuan; Shiau, Jun‐Ping; Farooqi, Ammad Ahmad; Tang, Jen‐Yang; Chen, Kuan‐Liang; Yen, Ching‐Yu; Chang, Hsueh‐Wei

doi:10.1002/tox.23951

Cited by 3 publications

(2 citation statements)

References 67 publications

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“…Two oral cancer cell lines were applied in this study, namely HSC-3 (JCR Bank, Ibaraki, Osaka, Japan) and OC-2 [ 63 ] (kindly given by Kaohsiung Medical University (Dr. Wan-Chi Tsai)). The cultural maintenance and medium preparation have been described previously [ 64 ]. Cell viability was evaluated with a CCK-8 reagent (IMT Formosa New Materials, Kaohsiung, Taiwan) [ 65 ] for 1 h.…”

Section: Methodsmentioning

confidence: 99%

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

Lu,

Chen,

Yen

et al. 2024

Pharmaceuticals

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The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow–Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

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Section: Methodsmentioning

confidence: 99%

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

Lu,

Chen,

Yen

et al. 2024

Pharmaceuticals

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“…TRAIL-resistant cancer cells have hyperactive survival signaling. Different natural and synthetic molecules have been tested to increase the sensitivity of cancer cells to TRAIL-based therapeutics (80)(81)(82)(83)(84).…”

Section: Trail-based Therapeutics Mediated Pyroptosismentioning

confidence: 99%

Mechanistic role of pyroptosis in tumor microenvironment and tumor immunotherapy

Rukset Attar,

Muhammad Zahid Qureshi,

Uteuliyev Yerzhan Sabitaliyevich

et al. 2024

Cell Mol Biol (Noisy-le-grand)

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In recent decades, extraordinary attention has been devoted to cell death pathways principally because of multifaceted regulatory roles in normal developmental and pathophysiological processes. The removal of functionally defective, infected or potentially malignant cells is regulated by programmed cell death (PCD) cascades. Pyroptotic cell death is a highly complicated pro-inflammatory form of cell death. Pyroptosis is characterized by the formation of pores in the plasma membrane by oligomerization of the N-terminal fragment of gasdermins (gasdermin-NT) following the cleavage of gasdermin. Pyroptosis plays a pivotal role in the innate immune responses and mechanistically steered by inflammasome-mediated and inflammasome-independent cascades. In this review, we have comprehensively analyzed how different signaling pathways regulated pyroptosis in cancer inhibition and metastatic spread of cancer cells to the secondary sites. Comprehensive understanding of the interconnection between signaling pathways and pyroptosis will enable us to reap maximum benefits from the exciting mechanistic insights gained from pioneering studies related to pyroptosis.

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Protein neddylation and its role in health and diseases

Zhang,

Yu,

et al. 2024

Sig Transduct Target Ther

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NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation, catalyzed by the enzyme cascade, namely NEDD8 activating enzyme (E1), NEDD8 conjugating enzyme (E2), and NEDD8 ligase (E3). The substrates of neddylation are categorized into cullins and non-cullin proteins. Neddylation of cullins activates CRLs (cullin RING ligases), the largest family of E3 ligases, whereas neddylation of non-cullin substrates alters their stability and activity, as well as subcellular localization. Significantly, the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases, such as metabolic disorders, liver dysfunction, neurodegenerative disorders, and cancers, among others. Thus, targeting neddylation becomes an attractive strategy for the treatment of these diseases. In this review, we first provide a general introduction on the neddylation cascade, its biochemical process and regulation, and the crystal structures of neddylation enzymes in complex with cullin substrates; then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates. We further review the literature data on dysregulated neddylation in several human diseases, particularly cancer, followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach. Finally, few perspectives were proposed for extensive future investigations.

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The neddylation inhibitor MLN4924 inhibits proliferation and triggers apoptosis of oral cancer cells but not for normal cells

Cited by 3 publications

References 67 publications

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

Mechanistic role of pyroptosis in tumor microenvironment and tumor immunotherapy

Protein neddylation and its role in health and diseases

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