Moscatilin Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma Cells via JNK Signaling Pathway

Abstract

Dendrobii Herba is an herbal medicine that uses the stems of Dendrobium species (Orchidacea). It has been traditionally used to treat fever, hydrodipsomania, stomach disorders, and amyotrophia. In our previous study, a bibenzyl compound, moscatilin, which is isolated from Dendrobii Herba, showed potent cytotoxicity against a FaDu human pharyngeal squamous carcinoma cell line. Prompted by this finding, we performed additional studies in FaDu cells to investigate the mechanism of action. Moscatilin induced FaDu cell death by using 5 μM of concentration and by mediating apoptosis, whereas cell proliferation following treatment with 1 μM of moscatilin was not suppressed to the same levels as by the anti-cancer agent, cisplatin. Apoptosis-related protein expression (cleaved caspase-8, cleaved caspase-7, cytochrome c, cleaved caspase-9, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) was increased by treating with 5 μM of moscatilin. This suggests that moscatilin-mediated apoptosis is associated with the extrinsic and intrinsic apoptotic signaling pathways. In addition, moscatilin-induced apoptosis was mediated by the c-Jun N-terminal kinase (JNK) signaling pathway. Overall, this study identified additional biological activity of moscatilin derived from natural products and suggested its potential application as a chemotherapeutic agent for the management of head and neck squamous cell carcinoma.

Mangiferin inhibits lipopolysaccharide‐induced epithelial‐mesenchymal transition (EMT) and enhances the expression of tumor suppressor gene PER1 in non‐small cell lung cancer cells

“…Apoptosis triggered by the caspase dependent pathway can be started off the extrinsic pathway or the intrinsic pathway (mitochondrial pathway). The extrinsic pathway leads to activation of caspase‐8 28 . As shown in Figure 1D, caspase‐8 increased obviously in NSCLC cells with mangiferin.…”

Chemical and Biological Profiles of Dendrobium in Two Different Species, Their Hybrid, and Gamma-Irradiated Mutant Lines of the Hybrid Based on LC-QToF MS and Cytotoxicity Analysis

“…In conclusion, the chemical compositions of Dendrobii Herba, D. nobile, D. chrysanthum, and their hybrid, D. nobile × candidum, were analyzed via UPLC-QToF MS and were identified by comparing the ESI QToF MS data of the isolates (1-13) from Dendrobii Herba and the standards (14)(15)(16)(17). The results showed that the chemical compositions of each sample were different, demonstrating that each sample from different species could be well-distinguished, and the quality of the different samples could be determined through this method.…”

“…The methanol extracts of Dendrobii Herba, D. nobile, D. candidum, the hybrid, D. nobile × candidum, and compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) were analyzed using a Waters ACQUITY UPLC I-Class system combined with a Vion IMS QToF mass spectrometer (Waters). Each sample (1000 ppm, 2 µL) was injected into an ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm i.d., 1.7 µm; Waters).…”

“…Previous phytochemical studies on the Dendrobium species have resulted in the isolation of diverse types of compounds, such as alkaloids [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ], bibenzyls [ 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ], phenanthrenes [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], fluorenones [ 18 , 31 ], sesquiterpenoids [ 6 , 32 , 33 ], lignans [ 21 , 34 ], flavonoids [ 35 , 36 ], and polysaccharides [ 37 , 38 , 39 ]. These compounds have been reported as exhibiting neuroprotective [ 4 , 5 ], anticancer [ 6 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 25 , …”

Traditional Herbal Medicine Mediated Regulations during Head and Neck Carcinogenesis

“…At the molecular level, THM compounds seem to regulate tumorous properties through modulation of different external and intrinsic apoptotic signaling pathways. For instance, berberine, demethoxycurcumin, ursolic acid, tanshinones, oridonin, moscatilin and wogonin were all capable of suppressing oncogenic PI3K/Akt/mTOR and MAPK/JNK/p38 pathways thereby resulting in cell proliferation inhibition in HNSCC as well as in nasopharyngeal carcinoma [13,[22][23][24][25][26][27][28]. Moreover, mitochondrial-associated apoptotic regulators BCL-2 and Bax were also important mediators for THM-related antigrowth/survival activity.…”