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Cancer Chemotherapy and Pharmacology

Published in:

01-08-2021 | Original Article

Glaucocalyxin A induces apoptosis and autophagy in tongue squamous cell carcinoma cells by regulating ROS

Authors: Fanzhe Shi, Danfeng Xue, Qingkun Jiang, Jiaxuan Qiu

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2021

Abstract

Purpose

Tongue squamous cell carcinoma (TSCC) is the most common highly invasive oral cancer. Glaucocalyxin A (GLA) is a diterpenoid component isolated from Rabdosia japonica var. with anti-bacterial and anti-cancer biological properties. However, the role of GLA in human TSCC remains uncertain. The aim of this paper was to investigate the anti-cancer effect of GLA on TSCC cells as well as its underlying mechanism.

Methods

Cell viability and growth were analyzed by CCK-8 assay and colony formation, respectively. DAPI staining and flow cytometry assay were used to detect the cell apoptosis. Lysotracker Red staining was used to observe the lysosomes and autolysosomes of TSCC cells. ROS fluorescent probe was used to test the intracellular ROS levels. Western blotting was used to detect the expression levels of apoptosis- and autophagy-related proteins.

Results

GLA inhibits the cell viability and growth in TSCC cells. GLA induces TSCC cells apoptosis, autophagy and ROS production in a time- and concentration-dependent manner. In addition, GLA inhibits the viability of TSCC cells by inducing intracellular ROS production. Finally, GLA triggers ROS-dependent apoptosis and autophagy in TSCC cells.

Conclusion

Our results consistently suggested that GLA can induce apoptosis and autophagy in TSCC cells by generating ROS. GLA may serve as a promising therapeutic drug for overcoming TSCC.

Bilano V, Gilmour S, Moffiet T, d’Espaignet ET, Stevens GA, Commar A, Tuyl F, Hudson I, Shibuya K (2015) Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO comprehensive information systems for tobacco control. Lancet 385:966–976CrossRef

Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD, King BA, Neff LJ (2016) Current cigarette smoking among adults—United States. Morb Mortal Wkly Rep 67(2018):53–59

Tota JE, Anderson WF, Coffey C, Califano J, Cozen W, Ferris RL, St John M, Cohen EE, Chaturvedi AK (2017) Rising incidence of oral tongue cancer among white men and women in the United States, 1973-2012. Oral Oncol 67:146–152CrossRef

Ng JH, Iyer NG, Tan MH, Edgren G (2017) Changing epidemiology of oral squamous cell carcinoma of the tongue: a global study. Head Neck 39:297–304CrossRef

Fan T, Pi H, Li M, Ren Z, He Z, Zhu F, Tian L, Tu M, Xie J, Liu M, Li Y, Tan M, Li G, Qing W, Reiter RJ, Yu Z, Wu H, Zhou Z (2018) Inhibiting MT2-TFE3-dependent autophagy enhances melatonin-induced apoptosis in tongue squamous cell carcinoma. J Pineal Res 64:e12457CrossRef

Dong Z, Gao Q, Guo H (2018) Glaucocalyxin A attenuates the activation of hepatic stellate cells through the TGF-β1/smad signaling pathway. DNA Cell Biol 37:227–232CrossRef

Gao LW, Zhang J, Yang WH, Wang B, Wang JW (2011) Glaucocalyxin A induces apoptosis in human leukemia HL-60 cells through mitochondria-mediated death pathway. Toxicol In Vitro 25:51–63CrossRef

Mao M, Zhang T, Wang Z, Wang H, Xu J, Yin F, Wang G, Sun M, Wang Z, Hua Y, Cai Z (1865) Glaucocalyxin A-induced oxidative stress inhibits the activation of STAT3 signaling pathway and suppresses osteosarcoma progression in vitro and in vivo. Biochim Biophys Acta Mol Basis Dis 2019:1214–1225

Zhu J, Sun Y, Lu Y, Jiang X, Ma B, Yu L, Zhang J, Dong X, Zhang Q (2018) Glaucocalyxin A exerts anticancer effect on osteosarcoma by inhibiting GLI1 nuclear translocation via regulating PI3K/Akt pathway. Cell Death Dis 9:708CrossRef

10.

Yang J, Liu Y, Xue C, Yu W, Zhang J, Qiao C (2014) Synthesis and biological evaluation of glaucocalyxin A derivatives as potential anticancer agents. Eur J Med Chem 86:235–241CrossRef

11.

Liu HC, Qiao LM, Zheng W, Xiang ZB, Chen HS, Yu SC, Zhang DZ, Wang T, Zhang YF, Jin YS (2020) Synthesis and cytotoxicity assessment of novel 7-O- and 14-O-derivatives of glaucocalyxin A. Anticancer Agents Med Chem 20:1241–1249CrossRef

12.

Sabharwal SS, Schumacker PT (2014) Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles’ heel? Nat Rev Cancer 14:709–721CrossRef

13.

Prasad S, Gupta SC, Tyagi AK (2017) Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals. Cancer Lett 387:95–105CrossRef

14.

Gaikwad S, Srivastava SK (2021) Role of phytochemicals in perturbation of redox homeostasis in cancer. Antioxidants (Basel) 10:83CrossRef

15.

Xue D, Pan ST, Zhou X, Ye F, Zhou Q, Shi F, He F, Yu H, Qiu J (2020) Plumbagin enhances the anticancer efficacy of cisplatin by increasing intracellular ROS in human tongue squamous cell carcinoma. Oxid Med Cell Longev 2020:5649174PubMedPubMedCentral

16.

Li F, Song L, Yang X, Huang Z, Mou X, Syed A, Bahkali AH, Zheng L (2020) Anticancer and genotoxicity effect of (Clausena lansium (Lour.) skeels) peel ZnONPs on neuroblastoma (SH-SY5Y) cells through the modulation of autophagy mechanism. J Photochem Photobiol B 203:111748CrossRef

17.

Kirkin V, Rogov VV (2019) A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. Mol Cell 76:268–285CrossRef

18.

Wang F, Gómez-Sintes R, Boya P (2018) Lysosomal membrane permeabilization and cell death. Traffic 19:918–931CrossRef

19.

Vega-Rubín-de-Celis S, Kinch L, Peña-Llopis S (2020) Regulation of beclin 1-mediated autophagy by oncogenic tyrosine kinases. Int J Mol Sci 21:9210CrossRef

20.

Xiang Z, Wu X, Liu X, Jin Y (2014) Glaucocalyxin A: a review. Nat Prod Res 28:2221–2236CrossRef

21.

Zhou X, Ma W, Li X, Xu J (2020) Glaucocalyxin a prevents hypoxia-induced epithelial-mesenchymal transition in human gastric cancer cells through the PI3K/Akt signaling pathway. J Recept Signal Transduct Res. https://doi.org/10.1080/10799893.2020.1853160

22.

Jiang X, Zhang Z, Song C, Deng H, Yang R, Zhou L, Sun Y, Zhang Q (2019) Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Chem Biol Interact 307:158–166CrossRef

23.

Radha G, Raghavan SC (1868) BCL2: a promising cancer therapeutic target. Biochim Biophys Acta Rev Cancer 2017:309–314

24.

Kopeina GS, Prokhorova EA, Lavrik IN, Zhivotovsky B (2018) Alterations in the nucleocytoplasmic transport in apoptosis: Caspases lead the way. Cell Prolif 51:e12467CrossRef

25.

Lin W, Xie J, Xu N, Huang L, Xu A, Li H, Li C, Gao Y, Watanabe M, Liu C, Huang P (2018) Glaucocalyxin A induces G2/M cell cycle arrest and apoptosis through the PI3K/Akt pathway in human bladder cancer cells. Int J Biol Sci 14:418–426CrossRef

26.

Liu Y, Lu S, Zhao L, Dong X, Zhu Z, Jin Y, Chen H, Lu F, Hong Z, Chai Y (2018) Effects of glaucocalyxin A on human liver cancer cells as revealed by GC/MS- and LC/MS-based metabolic profiling. Anal Bioanal Chem 410:3325–3335CrossRef

27.

White E, Mehnert JM, Chan CS (2015) Autophagy, metabolism, and cancer. Clin Cancer Res 21:5037–5046CrossRef

28.

Manent J, Banerjee S, de Matos Simoes R, Zoranovic T, Mitsiades C, Penninger JM, Simpson KJ, Humbert PO, Richardson HE (2017) Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species. Oncogene 36:5576–5592CrossRef

29.

Wang Y, Xiong H, Liu D, Hill C, Ertay A, Li J, Zou Y, Miller P, White E, Downward J, Goldin RD, Yuan X, Lu X (2019) Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells. Autophagy 15:886–899CrossRef

30.

White E, DiPaola RS (2009) The double-edged sword of autophagy modulation in cancer. Clin Cancer Res 15:5308–5316CrossRef

31.

Zhou T, Zhuang J, Wang Z, Zhou Y, Li W, Wang Z, Zhu Z (2019) Glaucocalyxin A as a natural product increases amyloid β clearance and decreases tau phosphorylation involving the mammalian target of rapamycin signaling pathway. NeuroReport 30:310–316CrossRef

32.

Harris IS, DeNicola GM (2020) The Complex Interplay between Antioxidants and ROS in Cancer. Trends Cell Biol 30:440–451CrossRef

33.

Salehi F, Jamali T, Kavoosi G, Ardestani SK, Vahdati SN (2020) Stabilization of Zataria essential oil with pectin-based nanoemulsion for enhanced cytotoxicity in monolayer and spheroid drug-resistant breast cancer cell cultures and deciphering its binding mode with gDNA. Int J Biol Macromol 164:3645–3655CrossRef

34.

Peng Z, Zhang R, Pan L, Pei H, Niu Z, Wang H, Lv J, Dang X (2020) Glaucocalyxin A protects H9c2 cells against hypoxia/reoxygenation-induced injury through the activation of Akt/Nrf2/HO-1 pathway. Cell Transpl 29:963689720967672CrossRef

Title: Glaucocalyxin A induces apoptosis and autophagy in tongue squamous cell carcinoma cells by regulating ROS
Authors: Fanzhe Shi
Danfeng Xue
Qingkun Jiang
Jiaxuan Qiu
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-021-04285-3

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Purpose

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