Ilimaquinone Induces Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma Cells

In this study, the anti-tumor activity of ilimaquinone (IQ), a sesquiterpene quinone isolated from marine sponge Halichondria sp., in oral squamous cell carcinoma (OSCC) cells, was investigated. IQ suppressed the viability of the OSCC cell lines SCC4 and SCC2095 with IC50 values of 7.5 and 8.5 μM, respectively. Flow cytometric analysis demonstrated that IQ induced caspase-dependent apoptosis in SCC4 cells and modulated the expression of several cell growth-related gene products, including Akt, p38, Mcl-1, and p53. Notably, p53 knockdown caused higher resistance to IQ’s anti-tumor activity. In addition, IQ increased reactive oxygen species generation, which was partially reversed by the addition of antioxidants. Furthermore, it triggered autophagy, as evidenced by acidic organelle formation and LC3B-II and Atg5 expression in SCC4 cells. Pretreatment with the autophagy inhibitor 3-methyladenine or chloroquine partially decreased IQ-induced apoptosis, suggesting that IQ induced protective autophagy. In summary, IQ has potential to be used in OSCC therapy.

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Correlation between histological grading and ploidy status in oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma: A flow cytometric analysis

Journal of Pharmacy And Bioallied Sciences ◽

10.4103/jpbs.jpbs_33_20 ◽

2020 ◽

Vol 12 (5) ◽

pp. 91

Author(s):

Surekha Velidandla ◽

Sangameshwar Manikya ◽

Nirosha Gajjada ◽

Sridhar Reddy ◽

Lavanya Gogulamudi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Oral Submucous Fibrosis ◽

Flow Cytometric Analysis ◽

Histological Grading ◽

Flow Cytometric ◽

Submucous Fibrosis ◽

Ploidy Status

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Invasive front in oral squamous cell carcinoma: Image and flow cytometric analysis with clinicopathologic correlation

Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology ◽

10.1067/moe.2002.122341 ◽

2002 ◽

Vol 93 (6) ◽

pp. 682-687 ◽

Cited By ~ 20

Author(s):

Makoto Noguchi ◽

Hisanori Kinjyo ◽

Gen-iku Kohama ◽

Kenji Nakamori

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Flow Cytometric Analysis ◽

Invasive Front ◽

Clinicopathologic Correlation ◽

Flow Cytometric

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Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21217947 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7947

Author(s):

Jing-Ru Weng ◽

Wei-Yu Lin ◽

Li-Yuan Bai ◽

Jing-Lan Hu ◽

Chia-Hsien Feng

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cardiac Glycoside ◽

Janus Kinase ◽

Parp Cleavage ◽

Diphenyltetrazolium Bromide ◽

Indigenous Plant ◽

Induced Apoptosis

We recently isolated a cardiac glycoside (CG), αldiginoside, from an indigenous plant in Taiwan, which exhibits potent tumor-suppressive efficacy in oral squamous cell carcinoma (OSCC) cell lines (SCC2095 and SCC4, IC50 < 0.2 µM; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays). Here, we report that αldiginoside caused Sphase arrest and apoptosis, through the inhibition of a series of signaling pathways, including those mediated by cyclin E, phospho-CDC25C (p-CDC25C), and janus kinase/signal transducer and activator of transcription (JAK/STAT)3. αldiginoside induced apoptosis, as indicated by caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. Equally important, αldiginoside reduced Mcl-1 expression through protein degradation, and overexpression of Mcl-1 partially protected SCC2095 cells from αldiginoside’s cytotoxicity. Taken together, these data suggest the translational potential of αldiginoside to foster new therapeutic strategies for OSCC treatment.

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