Trichodermin inhibits the growth of oral cancer through apoptosis-induced mitochondrial dysfunction and HDAC-2-mediated signaling

HDAC2 as a target for developing anti-cancer drugs

“…C-MYC increased the expression level of HDAC2 in PC cells [72] , implying that targeting HDAC2 might overcome c-MYC-induced oncogenic effects. Trichodermin, an inhibitor of eukaryotic protein synthesis, induced apoptosis by decreasing HDAC2 expression and levels of phosphorylated STAT3 and NF-κB [73] .…”

A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models

“…Nuclear factor-κappa B (NF-κB), a protein complex consisting of five transcription factors, namely RelA, RelB, c-Rel, NF-κB1, and NF-κB2, has been reported to play an important role in cell proliferation and survival in HNSCC [ 62 , 63 ]. Preclinical studies using HNSCC models have demonstrated the inhibition of NF-κB, leading to apoptosis with neferine, trichodermin, cinnamaldehyde, and Seco-A -ring oleanane [ 48 , 50 , 64 , 65 ].…”

“…The activation of STAT3 would also lead to various STAT3-dependent pathways, such as the interleukin-8/STAT3 (IL-8/STAT3) and EGFR/STAT3/SRY-box transcription factor 2 (EGFR/STAT3/SOX2) pathways, which have been shown to play important roles in cancer stemness [ 71 , 72 ]. Preclinical studies in HNSCC models have indicated the downregulation of p-STAT3 with trichodermin and Seco-A -ring oleanane [ 50 , 65 ]. Meanwhile, psorachromene caused the downregulation of EGFR, leading to apoptosis and inhibiting metastasis [ 24 ].…”

“…Actein, salicylate, honokiol, trichodermin, psorachromene, protocatechuic acid, fucoidan, hydroxygenkwanin, nimbolide, 4-O-methylhonokiol, [(3β)-3-hydroxy-lup-20(29)-en-28-oic acid], seco-A-ring oleanane, cinnamaldehyde, kaempferol, resveratrol, and curcumin induced cell cycle arrest via the regulation of cyclins and Cdks, which play an important role in coordinating the cell cycle progression [ 24 , 41 , 42 , 45 , 47 , 48 , 49 , 50 , 56 , 65 , 91 , 92 , 107 , 108 ]. The expressions of p21, p27, p16, and p53, acting as cyclin-Cdk complex inhibitors, have also been upregulated by actein, hydroxygenkwanin, honokiol, ilimaquinone, tanshinone IIA, resveratrol, and curcumin, which leads to induced cell cycle arrest [ 41 , 43 , 45 , 46 , 107 , 108 ].…”

“…Cell migration and angiogenesis have been widely studied and strongly associated with regulations of MMPs. Fucoidan, trichodermin, [(3β)-3-hydroxy-lup-20(29)-en-28-oic acid], seco-A-ring oleanane, and sodium danshensu have shown to downregulate MMPs, which inhibit cell migration and angiogenesis in HNSCC [ 49 , 50 , 55 , 65 ]. The VEGF and VEGF receptors play an important role in coordinating angiogenesis, while ilimaquinone, cinnamaldehyde, [(3β)-3-hydroxy-lup-20(29)-en-28-oic acid], and seco-A-ring oleanane have shown inhibition of the VEGF signaling in vitro [ 46 , 48 , 50 ].…”