In vitro evaluation of the pogostone effects on the expression of PTEN and DACT1 tumor suppressor genes, cell cycle, and apoptosis in ovarian cancer cell line

Mansour Homayoun , Nayereh Sajedi, Mitra Soleimani


Background and purpose: Ovarian cancer is one of the most dangerous cancers among women. Pogostone has anticancer effects and is rich in polyphenol compounds. In the present study, we investigated the effects of pogostone on ovarian cancer cell lines (OVCAR-3).

Experimental approach: OVCAR-3 cells were treated with pogostone at IC50 (90 μg/mL) for 24 and 48 h. Cell viability and apoptotic rate in the cells were measured using MTT assay and flow cytometry. Real-time PCR was used to determine the expression of genes involved in the cell cycle and apoptosis. The expression of caspase-3 (CASP3) protein was evaluated by the CASP3 assay.

Findings/Results: Treatment of OVCAR-3 cells with pogostone increased the expression levels of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and Dapper antagonist of catenin-1 (DACT1) tumor suppressor genes, as well as the apoptotic genes CASPs3, 8, and 9. Moreover, the ratio of the expressed BCL2 associated X (BAX)/BCl2 genes, as pro- and anti-apoptotic genes, was increased. The expression levels of the genes related to the cell cycle progression including cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4) were inhibited. The data obtained from flow cytometry indicated that pogostone induced cell apoptosis in 24 and 48 pogostone groups. The CASP3 colorimetric assay revealed that pogostone increased the expression of CASP3 protein in the treated groups.

Conclusion and implication: Pogostone, by inducing the expression of PTEN and DACT1 tumor suppressor genes and regulation of downstream genes may decrease cell proliferation and increase the rate of apoptosis in OVCAR-3.


Apoptosis; Cell cycle; DACT1; Ovarian cancer; Pogostone; PTEN.

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Homayoun M, Ghasemnezhad Targhi R, Soleimani M. Anti-proliferative and anti-apoptotic effects of grape seed extract on chemo-resistant OVCAR-3 ovarian cancer cells. Res Pharm Sci. 2020;15(4):390-400.

DOI: 10.4103/1735-5362.293517

Pokhriyal R, Hariprasad R, Kumar L, Hariprasad G. Chemotherapy resistance in advanced ovarian cancer patients. Biomark Cancer. 2019;11:1179299X19860815,1-19.

DOI: 10.1177/1179299X19860815.

Chan KKL, Yao TJ, Jones B, Zhao JF, Ma F, Leung C, et al. The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring. Ann Oncol. 2011;22(10):2241-2249.

DOI: 10.1093/annonc/mdq749.

Safarzadeh E, Shotorbani SS, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 2014;4(Suppl 1):421-427.

DOI: 10.5681/apb.2014.062.

Li RN, Liu B, Li XM, Hou LS, Mu XL, Wang H, et al. DACT1 overexpression in type I ovarian cancer inhibits malignant expansion and cis-platinum resistance by modulating canonical Wnt signalling and autophagy. Sci Rep. 2017;7:9285,1-12.

DOI: 10.1038/s41598-017-08249-7.

Jafari SM, Nazri A, Shabani M, Zargar Balajam N, Aghaei M. Galectin-9 induces apoptosis in OVCAR-3 ovarian cancer cell through mitochondrial pathway. Res Pharm sci. 2018;13(6):557-565.

DOI: 10.4103/1735-5362.245967.

Raoufi-Nejad K, Javadi M, Torkamandi H, Rajabi M, Moeini A, Khanavi M, et al. Adverse drug reactions of herbal medicines during pregnancy amongst Iranian women. Res Pharm Sci. 2012; 7(5):S980.

Tsai CC, Chang YH, Chang CC, Cheng YM, Ou YC, Chien CCC, et al. Induction of apoptosis in endometrial cancer (ishikawa) cells by Pogostemon cablin aqueous extract (PCAE). Int J Mol Sci. 2015;16(6):12424-12435.

DOI: 10.3390/ijms160612424.

Dongare P, Dhande S, Kadam V. A review on Pogostemon patchouli. Res J Pharmacognosy Phytochem. 2013;6(1):41-47.

DOI: 10.5958/0975-4385.

Dechayont B, Ruamdee P, Poonnaimuang S, Mokmued K, Chunthorng-Orn J. Antioxidant and antimicrobial activities of Pogostemon cablin (Blanco) Benth. J Bot. 2017;2017:8310275,1-7.

DOI: 10.1155/2017/8310275.

Li YC, Xian YF, Su ZR, Ip SP, Xie JH, Liao JB, et al. Pogostone suppresses proinflammatory mediator production and protects against endotoxic shock in mice. J Ethnopharmacol. 2014;157: 212-221.

DOI: 10.1016/j.jep.2014.09.023.

Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol. 2014;4:64-74.

DOI: 10.3389/fonc.2014.00064.

Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annual Rev Pathol. 2009;4:127-150.

DOI: 10.1146/annurev.pathol.4.110807.092311.

Takei Y, Saga Y, Mizukami H, Takayama T, Ohwada M, Ozawa K, et al. Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice. Mol Cancer Ther. 2008;7(3):704-711.

DOI: 10.1158/1535-7163.

Cao ZX, Yang YT, Yu S, Li YZ, Wang WW, Huang J, et al. Pogostone induces autophagy and apoptosis involving PI3K/Akt/mTOR axis in human colorectal carcinoma HCT116 cells. J Ethnopharmacol. 2017;202:20-27.

DOI: 10.1016/j.jep.2016.07.028.

Gasparri ML, Bardhi E, Ruscito I, Papadia A, Farooqi AA, Marchetti C, et al. PI3K/AKT/mTOR pathway in ovarian cancer treatment: are we on the right track? Geburtshilfe Frauenheilkd. 2017;77(10): 1095-1103.

DOI: 10.1055/s-0043-118907.

Zhu K, Jiang B, Yang Y, Hu R, Liu Z. DACT1 overexpression inhibits proliferation, enhances apoptosis, and increases daunorubicin chemosensitivity in KG-1α cells. Tumor Biol. 2017;39(10):1010428317711089,1-8.

DOI: 10.1177/1010428317711089.

Olmeda D, Castel S, Vilaró S, Cano A. Beta-catenin regulation during the cell cycle: implications in G2/M and apoptosis. Mol Biol Cell. 2003;14(7):2844-2860.

DOI: 10.1091/mbc.e03-01-0865.

Velmurugan B, Singh RP, Kaul N, Agarwal R, Agarwal C. Dietary feeding of grape seed extract prevents intestinal tumorigenesis in APCmin/+ mice. Neoplasia. 2010;12(1):95-102.

DOI: 10.1593/neo.91718.

Jeong JB, Choi J, Lou Z, Jiang X, Lee SH. Patchouli alcohol, an essential oil of Pogostemon cablin, exhibits anti-tumorigenic activity in human colorectal cancer cells. Int Immunopharmacol. 2013;16(2):184-190.

DOI: 10.1016/j.intimp.2013.04.006.

Kruidering M, Evan GI. Caspase‐8 in apoptosis: the beginning of “the end”? IUBMB life. 2000;50(2): 85-90.

DOI: 10.1080/713803693.

Lu X, Yang L, Lu C, Xu Z, Qiu H, Wu J, et al. Molecular role of EGFR-MAPK pathway in patchouli alcohol-induced apoptosis and cell cycle arrest on a549 cells in vitro and in vivo. Biomed Res Int. 2016;2016:4567580,1-12.

DOI: 10.1155/2016/4567580.

Hamilton TC, Young RC, McKoy WM, Grotzinger KR, Green JA, Chu EW, et al. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983;43(11):5379-5389.

PMID: 6604576.

Beaufort CM, Helmijr JC, Piskorz AM, Hoogstraat M, Ruigrok-Ritstier K, Besselink N, et al. Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes. PloS One. 2014;9(9):e103988,1-16.

DOI: 10.1371/journal.pone.0103988.

Ghatei N, Nabavi AS, Toosi MHB, Azimian H, Homayoun M, Targhi RG, et al. Evaluation of bax, bcl-2, p21 and p53 genes expression variations on cerebellum of BALB/c mice before and after birth under mobile phone radiation exposure. Iran J Basic Med Sci. 2017;20(9):1037-1043.

DOI: 10.22038/IJBMS.2017.9273.

Cheaib B, Auguste A, Leary A. The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges. Chin J Cancer. 2015;34(1):4-16.

DOI: 10.5732/cjc.014.10289.

Nero C, Ciccarone F, Pietragalla A, Scambia G. PTEN and gynecological cancers. Cancers (Basel). 2019;11(10):1458-1474.

DOI: 10.3390/cancers11101458.

Russo A, Czarnecki AA, Dean M, Modi DA, Lantvit DD, Hardy L, et al. PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. Oncogene. 2018;37(15):1976-1990.

DOI: 10.1038/s41388-017-0097-8.

Saito M, Okamoto A, Kohno T, Takakura S, Shinozaki H, Isonishi S, et al. Allelic imbalance and mutations of the PTEN gene in ovarian cancer. Int J Cancer. 2000;85(2):160-165.

PMID: 10629071.

Cai J, Xu L, Tang H, Yang Q, Yi X, Fang Y, et al. The role of the PTEN/PI3K/Akt pathway on prognosis in epithelial ovarian cancer: a meta-analysis. Oncologist. 2014;19(5):528-535.

DOI: 10.1634/theoncologist.2013-0333.

Memmott RM, Dennis PA. Akt-dependent and-independent mechanisms of mTOR regulation in cancer. Cell Signal. 2009;21(5):656-664.

DOI: 10.1016/j.cellsig.2009.01.004.

Nguyen VHL, Hough R, Bernaudo S, Peng C. Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis. J Ovarian Res. 2019;12(1):122-138.

DOI: 10.1186/s13048-019-0596-z.

Arend RC, Londoño-Joshi AI, Straughn Jr JM, Buchsbaum DJ. The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013;131(3):772-779.

DOI: 10.1016/j.ygyno.2013.09.034.

Niiro E, Morioka S, Iwai K, Yamada Y, Ogawa K, Kawahara N, et al. Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer. Biomed Rep. 2018;8(3):215-223.

DOI: 10.3892/br.2018.1045.

Niu Y, Xu J, Sun T. Cyclin-dependent kinases 4/6 inhibitors in breast cancer: current status, resistance, and combination strategies. J Cancer. 2019;10(22):5504-5517.

DOI: 10.7150/jca.32628.

Gao C, Zhou Y, Li H, Cong X, Jiang Z, Wang X, et al. Antitumor effects of baicalin on ovarian cancer cells through induction of cell apoptosis and inhibition of cell migration in vitro. Mol Med Rep. 2017;16(6):8729-8734.

DOI: 10.3892/mmr.2017.7757.

He Z, Chen AY, Rojanasakul Y, Rankin GO, Chen YC. Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells. Oncol Rep. 2016; 35(1):291-297.

DOI: 10.3892/or.2015.4354.

Yu Z, Wan Y, Liu Y, Yang J, Li L, Zhang W. Curcumin induced apoptosis via PI3K/Akt-signalling pathways in SKOV3 cells. Pharm Biol. 2016;54(10):2026-2032.

DOI: 10.3109/13880209.2016.1139601.

Wang H, Zhang Z, Wei X, Dai R. Small-molecule inhibitor of Bcl-2 (TW-37) suppresses growth and enhances cisplatin-induced apoptosis in ovarian cancer cells. J Ovarian Res. 2015; 8(1):3-10.

DOI: 10.1186/s13048-015-0130-x.


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