<em>In vitro</em> induction of mitotic catastrophe as a therapeutic approach for oral cancer using the ethanolic extract of <em>Juniperus squamata</em>

Jung,Minjung; Han,Dae Jin; Ahn,Chi-Hyun; Hong,Kyoung-Ok; Choi,Youn Soo; Kim,Jun Sung; Yoon,Hye-Jung; Hong,Seong Doo; Shin,Ji-Ae; Cho,Sung-Dae

doi:10.3892/or.2021.8054

In vitro induction of mitotic catastrophe as a therapeutic approach for oral cancer using the ethanolic extract of Juniperus squamata

Authors:
- Minjung Jung
- Dae Jin Han
- Chi-Hyun Ahn
- Kyoung-Ok Hong
- Youn Soo Choi
- Jun Sung Kim
- Hye-Jung Yoon
- Seong Doo Hong
- Ji-Ae Shin
- Sung-Dae Cho
View Affiliations

Affiliations: Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea, Department of Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, Research and Development Center, H‑MED Incorporated, Seoul 03761, Republic of Korea
Published online on: April 16, 2021 https://doi.org/10.3892/or.2021.8054
Article Number: 103

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mitotic catastrophe, a cell death mechanism characterized by abnormal mitosis, has been regarded as a therapeutic approach for the development of anti‑cancer drug candidates. The aim of the present study was to investigate the potential effect of the ethanolic extract of Juniperus squamata (EEJS) on the occurrence of mitotic catastrophe in human oral cancer cell lines. The effect of EEJS on the occurrence of mitotic catastrophe was evaluated by measuring cytotoxicity, observing phase‑contrast or transmission electron microscope findings, evaluating the appearance of microtubule or chromosome abnormalities, and detecting the phosphorylation of histone H3 (Ser¹⁰). The apoptotic effect of EEJS was assessed by detecting cleaved PARP, analyzing the sub‑G₁ population, Annexin V‑FITC/PI double staining, western blot analysis, and the transient transfection of myeloid cell leukemia‑1 (Mcl‑1) overexpression vectors. EEJS treatment was effective in inhibiting cell proliferation in human oral cancer cell lines. EEJS resulted in the enrichment of enlarged multinucleated cells, the disturbance of microtubule formation, and increased phosphorylation of histone H3 (Ser¹⁰), which demonstrates the occurrence of mitotic catastrophe. Additionally, the multinucleated cells underwent apoptotic cell death in a cell context‑dependent manner, which was associated with the reduction of Mcl‑1 protein levels. Findings of the present study indicate that EEJS could be effective for treating human oral cancer by promoting mitotic catastrophe linked to apoptotic cell death.

View Figures

View References

1	Yao Y and Dai W: Genomic instability and cancer. J Carcinog Mutagen. 5:10001652014.PubMed/NCBI
2	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
3	Mc Gee MM: Targeting the mitotic catastrophe signaling pathway in cancer. Mediators Inflamm. 2015:1462822015. View Article : Google Scholar : PubMed/NCBI
4	Vitale I, Galluzzi L, Castedo M and Kroemer G: Mitotic catastrophe: A mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol. 12:385–392. 2011. View Article : Google Scholar : PubMed/NCBI
5	Kimura M, Yoshioka T, Saio M, Banno Y, Nagaoka H and Okano Y: Mitotic catastrophe and cell death induced by depletion of centrosomal proteins. Cell Death Dis. 4:e6032013. View Article : Google Scholar : PubMed/NCBI
6	Vakifahmetoglu H, Olsson M and Zhivotovsky B: Death through a tragedy: Mitotic catastrophe. Cell Death Differ. 15:1153–1162. 2008. View Article : Google Scholar : PubMed/NCBI
7	Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R and Kroemer G: Cell death by mitotic catastrophe: A molecular definition. Oncogene. 23:2825–2837. 2004. View Article : Google Scholar : PubMed/NCBI
8	Denisenko TV, Sorokina IV, Gogvadze V and Zhivotovsky B: Mitotic catastrophe and cancer drug resistance: A link that must to be broken. Drug Resist Updat. 24:1–12. 2016. View Article : Google Scholar : PubMed/NCBI
9	Qi M, Yao G, Fan S, Cheng W, Tashiro S, Onodera S and Ikejima T: Pseudolaric acid B induces mitotic catastrophe followed by apoptotic cell death in murine fibrosarcoma L929 cells. Eur J Pharmacol. 683:16–26. 2012. View Article : Google Scholar : PubMed/NCBI
10	Wu YC, Yen WY, Ho HY, Su TL and Yih LH: Glyfoline induces mitotic catastrophe and apoptosis in cancer cells. Int J Cancer. 126:1017–1028. 2010.PubMed/NCBI
11	Cragg GM and Pezzuto JM: Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract. 25 (Suppl 2):S41–S59. 2016. View Article : Google Scholar : PubMed/NCBI
12	Bais S, Gill NS, Rana N and Shandil S: A phytopharmacological review on a medicinal plant: Juniperus communis. Int Sch Res Notices. 2014:6347232014.PubMed/NCBI
13	Tavares WR and Seca AML: The current status of the pharmaceutical potential of Juniperus L. Metabolites. Medicines (Basel). 5:812018. View Article : Google Scholar : PubMed/NCBI
14	Raasmaja A, Stenius U and Ghalali A: The Water Extract of Juniperus communis L. Induces cell death and sensitizes cancer cells to cytostatic drugs through p53 and PI3K/Akt Pathways. Int J Mol Sci. 20:20542019. View Article : Google Scholar : PubMed/NCBI
15	Lee CC, Hsiao CY, Lee SC, Huang XF, Chang KF, Lee MS, Hsieh MC and Tsai NM: Suppression of oral cancer by induction of cell cycle arrest and apoptosis using Juniperus communis extract. Biosci Rep. 40:BSR202020832020. View Article : Google Scholar : PubMed/NCBI
16	Al Groshi A, Jasim HA, Evans AR, Ismail FMD, Dempster NM, Nahar L and Sarker SD: Growth inhibitory activity of biflavonoids and diterpenoids from the leaves of the Libyan Juniperus phoenicea against human cancer cells. Phytother Res. 33:2075–2082. 2019. View Article : Google Scholar : PubMed/NCBI
17	Yang IH, Jung W, Kim LH, Shin JA, Cho NP, Hong SD, Hong KO and Cho SD: Nitidine chloride represses Mcl-1 protein via lysosomal degradation in oral squamous cell carcinoma. J Oral Pathol Med. 47:823–829. 2018. View Article : Google Scholar : PubMed/NCBI
18	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI
19	Tajmirriahi N, Razavi SM, Shirani S, Homayooni S and Gasemzadeh G: Evaluation of metastasis and 5-year survival in oral squamous cell carcinoma patients in Isfahan (2001–2015). Dent Res J (Isfahan). 16:117–121. 2019. View Article : Google Scholar : PubMed/NCBI
20	Omura K: Current status of oral cancer treatment strategies: Surgical treatments for oral squamous cell carcinoma. Int J Clin Oncol. 19:423–430. 2014. View Article : Google Scholar : PubMed/NCBI
21	Szturz P and Vermorken JB: Management of recurrent and metastatic oral cavity cancer: Raising the bar a step higher. Oral Oncol. 101:1044922020. View Article : Google Scholar : PubMed/NCBI
22	Crooker K, Aliani R, Ananth M, Arnold L, Anant S and Thomas SM: A review of promising natural chemopreventive agents for head and neck cancer. Cancer Prev Res (Phila). 11:441–450. 2018. View Article : Google Scholar : PubMed/NCBI
23	Yu HJ, Shin JA, Yang IH, Won DH, Ahn CH, Kwon HJ, Lee JS, Cho NP, Kim EC, Yoon HJ, et al: Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation. Arch Oral Biol. 84:94–99. 2017. View Article : Google Scholar : PubMed/NCBI
24	Yang IH, Shin JA, Lee KE, Kim J, Cho NP and Cho SD: Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2AX. Eur J Oral Sci. 125:438–443. 2017. View Article : Google Scholar : PubMed/NCBI
25	Morse DL, Gray H, Payne CM and Gillies RJ: Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells. Mol Cancer Ther. 4:1495–1504. 2005. View Article : Google Scholar : PubMed/NCBI
26	Lin YW, Raj EN, Liao WS, Lin J, Liu KK, Chen TH, Cheng HC, Wang CC, Li LY, Chen C and Chao JI: Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition. Sci Rep. 7:98142017. View Article : Google Scholar : PubMed/NCBI
27	Tan S, Guan X, Grun C, Zhou Z, Schepers U and Nick P: Gallic acid induces mitotic catastrophe and inhibits centrosomal clustering in HeLa cells. Toxicol In Vitro. 30:506–513. 2015. View Article : Google Scholar : PubMed/NCBI
28	Levrier C, Rockstroh A, Gabrielli B, Kavallaris M, Lehman M, Davis RA, Sadowski MC and Nelson CC: Discovery of thalicthuberine as a novel antimitotic agent from nature that disrupts microtubule dynamics and induces apoptosis in prostate cancer cells. Cell Cycle. 17:652–668. 2018. View Article : Google Scholar : PubMed/NCBI
29	Qu Z, Zou X, Zhang X, Sheng J, Wang Y, Wang J, Wang C and Ji Y: Chelidonine induces mitotic slippage and apoptotic-like death in SGC-7901 human gastric carcinoma cells. Mol Med Rep. 13:1336–1344. 2016. View Article : Google Scholar : PubMed/NCBI
30	Kundu S, Kim TH, Yoon JH, Shin HS, Lee J, Jung JH and Kim HS: Viriditoxin regulates apoptosis and autophagy via mitotic catastrophe and microtubule formation in human prostate cancer cells. Int J Oncol. 45:2331–2340. 2014. View Article : Google Scholar : PubMed/NCBI
31	Yamaguchi R, Lartigue L and Perkins G: Targeting Mcl-1 and other Bcl-2 family member proteins in cancer therapy. Pharmacol Ther. 195:13–20. 2019. View Article : Google Scholar : PubMed/NCBI
32	Xiang W, Yang CY and Bai L: MCL-1 inhibition in cancer treatment. Onco Targets Ther. 11:7301–7314. 2018. View Article : Google Scholar : PubMed/NCBI
33	Wen Q, Zhan Y, Zheng H, Zang H, Luo J, Zhang Y, Wang W, Feng J, Lu J, Chen L and Fan S: Elevated expression of mcl-1 inhibits apoptosis and predicts poor prognosis in patients with surgically resected non-small cell lung cancer. Diagn Pathol. 14:1082019. View Article : Google Scholar : PubMed/NCBI
34	Hird AW and Tron AE: Recent advances in the development of Mcl-1 inhibitors for cancer therapy. Pharmacol Ther. 198:59–67. 2019. View Article : Google Scholar : PubMed/NCBI
35	Muller F, Cerella C, Radogna F, Dicato M and Diederich M: Effects of natural products on Mcl-1 expression and function. Curr Med Chem. 22:3447–3461. 2015. View Article : Google Scholar : PubMed/NCBI
36	Han JM, Hong KO, Yang IH, Ahn CH, Jin B, Lee W, Jung YC, Kim KA, Shin JA, Cho SD and Hong SD: Oridonin induces the apoptosis of mucoepidermoid carcinoma cell lines in a myeloid cell leukemia-1dependent manner. Int J Oncol. 57:377–385. 2020. View Article : Google Scholar : PubMed/NCBI
37	Keskes H, Belhadj S, Jlail L, El Feki A, Damak M, Sayadi S and Allouche N: LC-MS-MS and GC-MS analyses of biologically active extracts and fractions from Tunisian Juniperus phoenicea leaves. Pharm Biol. 55:88–95. 2017. View Article : Google Scholar : PubMed/NCBI
38	Pollio A, Zarrelli A, Romanucci V, Di Mauro A, Barra F, Pinto G, Crescenzi E, Roscetto E and Palumbo G: Polyphenolic profile and targeted bioactivity of methanolic extracts from mediterranean ethnomedicinal plants on human cancer cell lines. Molecules. 21:3952016. View Article : Google Scholar : PubMed/NCBI
39	Wedge DE, Tabanca N, Sampson BJ, Werle C, Demirci B, Baser KH, Nan P, Duan J and Liu Z: Antifungal and insecticidal activity of two Juniperus essential oils. Nat Prod Commun. 4:123–127. 2009.PubMed/NCBI