Umbelliferone exhibits anticancer activity via the induction of apoptosis and cell cycle arrest in HepG2 hepatocellular carcinoma cells

Yu,Shi‑Min; Hu,Dong‑Hui; Zhang,Jian‑Jun

doi:10.3892/mmr.2015.3797

Umbelliferone exhibits anticancer activity via the induction of apoptosis and cell cycle arrest in HepG2 hepatocellular carcinoma cells

Authors:
- Shi‑Min Yu
- Dong‑Hui Hu
- Jian‑Jun Zhang
View Affiliations

Affiliations: Department of Infective Disease, Zhongshan Hospital of Hubei, Wuhan, Hubei 430033, P.R. China
Published online on: May 18, 2015 https://doi.org/10.3892/mmr.2015.3797
Pages: 3869-3873

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

Hepatocellular carcinoma (HCC) is a highly malignant tumor, associated with poor patient prognoses, and high rates of morbidity and mortality. To date, the therapeutic strategies available for the treatment of HCC remain limited. The present study aimed to elucidate the anticancer activity of umbelliferone, a naturally occurring coumarin derivative isolated from Ferula communis, against the HepG2 HCC cell line. A 3‑(4,5‑dimthylthaizol‑2‑yl)‑2,5, diphenyltetrazolium bromide assay was used to evaluate cell viability following umbelliferone treatment, and the effects of umbelliferone on cell cycle progression and apoptosis were evaluated using flow cytometry. The presence of morphological features characteristic of apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation, were evaluated in HepG2 cells following umbelliferone treatment. Cell cycle analysis conducted via propidium iodide (PI) staining indicated that umbelliferone treatment induced cell cycle arrest at S phase in HepG2 cells. Analysis with Annexin V and PI staining revealed that umbelliferone induced apoptotic events in HepG2 cells in a concentration‑dependant manner (0‑50 µM). Umbelliferone also induced dose‑dependant DNA fragmentation. In conclusion, umbelliferone was found to exhibit significant anticancer effects via the induction of apoptosis, cell cycle arrest and DNA fragmentation in HepG2 cancer cells.

View Figures

View References

1	Filipova A, Seifrtova M, Mokry J, Dvorak J, Rezacova M, Filip S and Diaz-Garcia D: Breast cancer and cancer stem cells: A mini-review. Tumori. 100:363–369. 2014.PubMed/NCBI
2	Li ZF, Wang ZD, Ji YY, Zhang S, et al: Induction of apoptosis and cell cycle arrest in human HCC MHCC97H cells with Chrysanthemum indicum extract. World J Gastroenterol. 15:4538–4546. 2009. View Article : Google Scholar : PubMed/NCBI
3	Lu CX, Nan KJ, Nie YL, Hai YN and Jiao M: Delisheng, a Chinese medicinal compound, exerts anti-proliferative and pro-apoptotic effects on HepG2 cells through extrinsic and intrinsic pathways. Mol Biol Rep. 37:3407–3412. 2010. View Article : Google Scholar :
4	Roomi MW, Roomi NW, Kalinovsky T, Niedzwiecki A and Rath M: In vivo and in vitro effect of a nutrient mixture on human hepatocarcinoma cell line SK-HEP-1. Exp Oncol. 32:84–91. 2010.PubMed/NCBI
5	Newman DJ: Natural products as leads to potential drugs: An old process or the new hope for drug discovery? J Med Chem. 51:2589–2599. 2008. View Article : Google Scholar : PubMed/NCBI
6	Manosroi J, Sainakham M, Manosroi W and Manosroi A: Anti-proliferative and apoptosis induction activities of extract from Thai medicinal plant recipes selected from MANOSROI II database. J Ethnopharmacol. 141:451–459. 2012. View Article : Google Scholar : PubMed/NCBI
7	Engel N, Oppermanne C, Falodunb A and Kragle U: Proliferative effects of five traditional Nigerian medicinal plant extracts on human breast and bone cancer cell lines. J Ethnopharmacol. 137:1003–1010. 2011. View Article : Google Scholar : PubMed/NCBI
8	Tanaka H, Fujita N, Sugimoto R, Urawa N, et al: Hepatic oxidative DNA damage is associated with increased risk for hepatocellular carcinoma in chronic hepatitis C. Br J Cancer. 98:580–586. 2008. View Article : Google Scholar : PubMed/NCBI
9	Park SH, Lee Y, Han SH, Kwon SY, et al: Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma. BMC Cancer. 6:32006. View Article : Google Scholar : PubMed/NCBI
10	Chen YB, Yan ML, Gong JP, Xia RP, et al: Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1. Chinese Med J (Engl). 120:703–707. 2007.
11	Locher C, Conforti R, Aymeric L, Ma Y, et al: Desirable cell death during anticancer chemotherapy. Ann NY Acad Sci. 1209:99–108. 2010. View Article : Google Scholar : PubMed/NCBI
12	Jizhong Y and Shengqiang T: Preparative isolation and purification of two coumarins from Edgeworthia chrysantha lindl by high speed countercurrent chromatography. J Liq Chromatogr Relat Technol. 29:1307–1315. 2006. View Article : Google Scholar
13	Taraphdar AK, Roy M and Bhattacharya RK: Natural products as inducers of apoptosis: Implication for cancer therapy and prevention. Current Sci. 80:1387–1396. 2001.
14	Yu HY, Zhang XQ, Li X, Zeng FB and Ruan HL: 2-methoxyjuglone induces apoptosis in HepG2 human hepatocellular carcinoma cells and exhibits in vivo antitumor activity in a H22 mouse hepatocellular carcinoma model. J Nat Prod. 76:889–895. 2013. View Article : Google Scholar : PubMed/NCBI
15	Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, et al: Features of apoptotic cells measured by flow cytometry. Cytometry. 13:795–808. 1992. View Article : Google Scholar : PubMed/NCBI
16	Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C: A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Meth. 139:271–279. 1991. View Article : Google Scholar
17	Mukherjee AK, Basu S, Sarkar N and Ghosh AC: Advances in cancer therapy with plant based natural products. Curr Med Chem. 8:1467–1486. 2001. View Article : Google Scholar : PubMed/NCBI
18	Wang S, Penchala S, Prabhu S, Wang J and Huang Y: Molecular basis of traditional Chinese medicine in cancer chemoprevention. Curr Drug Discov Technol. 7:67–75. 2010. View Article : Google Scholar : PubMed/NCBI
19	Desai AG, Qazi GN, Ganju RK, El-Tame M, et al: Medicinal plants and cancer chemoprevention. Curr Drug Metab. 9:581–591. 2008. View Article : Google Scholar : PubMed/NCBI
20	Lorenzetti OJ, Boltralik J, Bushy E and Fortenberr B: The influence of protein vehicles on the penetrability of sunscreens. J Soc Cosmet Chem. 26:5931975.
21	Leal LK, Ferreira AA, Bezerra GA, Matos FJ and Viana GS: Antinociceptive, anti-inflammatory and bronchodilator activities of Brazilian medicinal plants containing coumarin: a comparative study. J Ethnopharmacol. 70:151–159. 2000. View Article : Google Scholar : PubMed/NCBI
22	Lino CS, Taveira ML, Viana GSB and Matos FJA: Analgesic and antiinflammatory activities of Justicia pectoralis Jacq and its main constituents: coumarin and umbelliferone. Phytother Res. 11:211–215. 1997. View Article : Google Scholar
23	Stefanova TH, Nikolova NJ, Toshkova RA and Neychev HO: Antitumor and immunomodulatory effect of coumarin and 7-hydroxycoumarin against Sarcoma 180 in mice. J Exp Ther Oncol. 6:107–115. 2007.PubMed/NCBI
24	Kielbus M, Skalicka-Wozniak K, Grabarska A, Jeleniewicz W, et al: 7-substituted coumarins inhibit proliferation and migration of laryngeal cancer cells in vitro. Anticancer Res. 33:4347–4356. 2013.PubMed/NCBI
25	Maucher A and von Angerer E: Antitumour activity of coumarin and 7-hydroxycoumarin against 7,12-dimethylbenz[a] anthracene-induced rat mammary carcinomas. J Cancer Res Clin Oncol. 120:502–504. 1994. View Article : Google Scholar