Licochalcone C induced apoptosis in human oral squamous cell carcinoma cells by regulation of the JAK2/STAT3 signaling pathway

Abstract

Oral cancer is of an aggressive malignancy that arises on oral cavity and lip, 90% of cancers histologically originated in the squamous cells. Licochalcone (LC)C has been known as natural phenolic chalconoid substances, and its origin is the root of Glycyrrhiza glabra or Glycyrrhiza inflata. LCC inhibited oral squamous cell carcinoma (OSCC) cell viability, mitochondrial function, and anchorage-independent growth in a dose-dependent manner. To investigate the ability of LCC to target Janus kinase 2 (JAK2), we performed pull-down binding assay, kinase assay, and docking simulation. The molecular docking studies were performed between JAK2 and the potent inhibitor LCC. It was shown that LCC tightly interacted with ATP-binding site of JAK2. In addition, LCC inhibited the JAK2/signal transducer and activator of transcription 3 pathway, upregulated p21, and downregulated Bcl-2, Mcl-1, and Survivin, while it disrupted mitochondrial membrane potential and subsequently caused cytochrome c release with activation of multi-caspase, eventually leading to apoptosis in HN22 and HSC4 cells. LCC elevated the protein levels of Bax, cleaved Bid and PARP, and increased Apaf-1, and this effect was reversed by LCC treatment. Our results demonstrated that treatment of OSCC cells with LCC induced the death receptor (DR)4 and DR5 expression level with the generation of reactive oxygen species and the upregulation of CHOP protein expression. Taken together, these results could provide the basis for clinical application as a new therapeutic strategy in the treatment of oral cancer.

Tyrosinase Inhibition Antioxidant Effect and Cytotoxicity Studies of the Extracts of Cudrania tricuspidata Fruit Standardized in Chlorogenic Acid

“…Human melanoma cells (B16F10) were purchased from the American Tissue Culture Collection (Manassas, VA, USA). Cells were seeded in 96-well plates and treated with 100 μg/mL of sample for 24 h. MTT was added and plates were incubated at 37 °C for 2 h. After dissolving the formazan crystals in 100 μL of DMSO, the absorbance was measured at 490 nm using an Enspire Multimode Plate reader (Perkin-Elmer, Akron, OH) [19].…”

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

“…Additionally, other lichochalcones including licochalcone H, C, and D have also been described as inhibitors of JAK/STAT signaling in oral squamous cell carcinoma [ 223 , 224 , 225 ].…”

Protein overexpression of toll‑like receptor 4 and myeloid differentiation factor 88 in oral squamous cell carcinoma and clinical significance

“…Oral cancer is a malignant tumor type that occurs in the lips or mouth ( 1 ). 90% of oral cancers are histologically originated from squamous cells ( 2 ) and oral cancer has traditionally been defined as oral squamous cell carcinoma (OSCC) ( 3 ). According to US government statistics, OSCC is the eighth most common cancer type among males and the 14th most common cancer type among females ( 4 ).…”

“…MyD88 is a central regulator of innate immunity; it acts directly downstream of TLRs and cytokine receptors, while also associated with carcinogenesis ( 12 ). MyD88 activates the TLRs or interleukin-1 receptor (IL-1Rs) pathways autonomously, or perhaps in relation to TNF receptor-associated factor 6 signaling, allowing tumor cells to proliferate indefinitely ( 3 ). MyD88 is involved in oncogene-induced inflammation and contributes to the development of cancers of the skin, liver, pancreas and colon, as well as sarcoma formation ( 13 ), and its expression is associated with poor prognosis in colorectal cancer ( 14 ).…”