Pteisolic acid G, a novel ent‑kaurane diterpenoid, inhibits viability and induces apoptosis in human colorectal carcinoma cells

Qiu,Shuangli; Wu,Xin; Liao,Hongbo; Zeng,Xiaobin; Zhang,Senwang; Lu,Xiaofen; He,Xiaohong; Zhang,Xiaoqi; Ye,Wencai; Wu,Hua; Zhu,Xiaohui

doi:10.3892/ol.2017.6889

Pteisolic acid G, a novel ent‑kaurane diterpenoid, inhibits viability and induces apoptosis in human colorectal carcinoma cells

Authors:
- Shuangli Qiu
- Xin Wu
- Hongbo Liao
- Xiaobin Zeng
- Senwang Zhang
- Xiaofen Lu
- Xiaohong He
- Xiaoqi Zhang
- Wencai Ye
- Hua Wu
- Xiaohui Zhu
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Affiliations: Cancer Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China, Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: September 6, 2017 https://doi.org/10.3892/ol.2017.6889
Pages: 5540-5548

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Abstract

Human colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, and its incidence rates are increasing in economical transitioning areas globally. To develop efficient chemotherapy drugs for CRC, the present study isolated and identified a novel ent‑kaurane diterpenoid from Pteris semipinnata, termed pterisolic acid G (PAG). This ent‑kaurane diterpenoid was demonstrated to significantly inhibit the growth of human CRC HCT116 cells in a time‑ and dose‑dependent manner, determined using the Cell Counting Kit‑8 assay. Additionally, western blot analysis, Hoechst 33342 staining and cytometry analysis revealed that PAG not only inhibited the viability of HCT116 cells by suppressing the dishevelled segment polarity protein 2/glycogen synthase kinase 3 β/β‑catenin pathway, but also induced the apoptosis of HCT116 cells by downregulating nuclear factor‑κB p65 activity, stimulating p53 expression and promoting the generation of intracellular reactive oxygen species. These results suggest that PAG, a novel inhibitor of the Wnt/β‑catenin pathway and inducer of apoptosis, should be investigated in more detail using in vivo experiments and comprehensive mechanistic studies in order to examine the potential use of PAG as a novel therapeutic agent for the treatment of CRC.

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1	Brenner H, Kloor M and Pox CP: Colorectal cancer. Lancet. 383:1490–1502. 2014. View Article : Google Scholar : PubMed/NCBI
2	Center MM, Jemal A and Ward E: International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 18:1688–1694. 2009. View Article : Google Scholar : PubMed/NCBI
3	Jemal A, Center MM, DeSantis C and Ward EM: Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 19:1893–1907. 2010. View Article : Google Scholar : PubMed/NCBI
4	Fearon ER: Molecular genetics of colorectal cancer. Annu Rev Pathol. 6:479–507. 2011. View Article : Google Scholar : PubMed/NCBI
5	DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS and Jemal A: Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 64:252–271. 2014. View Article : Google Scholar : PubMed/NCBI
6	Merla A and Goel S: Novel drugs targeting the epidermal growth factor receptor and its downstream pathways in the treatment of colorectal cancer: A systematic review. Chemother Res Pract. 2012:3871722012.PubMed/NCBI
7	Perkins G and Laurent-Puig P: Colorectal cancer biology. Rev Prat. 65:802–806. 2015.(In French). PubMed/NCBI
8	Zeng Y, Xie H, Qiao Y, Wang J, Zhu X, He G, Li Y, Ren X, Wang F, Liang L and Ding Y: FMNL2 regulates Rho/ROCK pathway to promote actin assembly and cell invasion of colorectal cancer. Cancer Sci. 106:1385–1393. 2015. View Article : Google Scholar : PubMed/NCBI
9	Jiang X, Tan J, Li J, Kivimäe S, Yang X, Zhuang L, Lee PL, Chan MT, Stanton LW, Liu ET, et al: DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. Cancer Cell. 13:529–541. 2008. View Article : Google Scholar : PubMed/NCBI
10	Cancer Genome Atlas Network: Comprehensive molecular characterization of human colon and rectal cancer. Nature. 487:330–337. 2012. View Article : Google Scholar : PubMed/NCBI
11	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
12	Meek DW: Regulation of the p53 response and its relationship to cancer. Biochem J. 469:325–346. 2015. View Article : Google Scholar : PubMed/NCBI
13	Basmadjian C, Zhao Q, Bentouhami E, Djehal A, Nebigil CG, Johnson RA, Serova M, de Gramont A, Faivre S, Raymond E and Désaubry LG: Cancer wars: Natural products strike back. Front Chem. 2:202014. View Article : Google Scholar : PubMed/NCBI
14	Liu CX, Yin QQ, Zhou HC, Wu YL, Pu JX, Xia L, Liu W, Huang X, Jiang T, Wu MX, et al: Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells. Nat Chem Biol. 8:486–493. 2012. View Article : Google Scholar : PubMed/NCBI
15	Sun HD, Huang SX and Han QB: Diterpenoids from Isodon species and their biological activities. Nat Prod Rep. 23:673–698. 2006. View Article : Google Scholar : PubMed/NCBI
16	Ye H, Liang NC and Zheng XB: Progress in research on anti-tumor effect of 5F isolated from Pteris semipinnata L. Nat Pro Res Dev. 26:2082–2087. 2014.
17	Schubert WM and Sweeney WA: The effect of ring strain on the ultraviolet spectra of α,β-unsaturated carbonyl compounds. J Am Chem Soc. 77:2297–2300. 1955. View Article : Google Scholar
18	Wang F, Li YJ, Ren FC, Wei GZ and Liu JK: Pterisolic acids A-F, new ent-kaurane diterpenoids from the fern Pteris semipinnata. Chem Pharm Bull (Tokyo). 59:484–487. 2011. View Article : Google Scholar : PubMed/NCBI
19	Hutchison M, Lewer P and MacMillan J: Carbon-13 nuclear magnetic resonance spectra of eighteen derivatives of ent-kaur-16-en-19-oic acid. J Chem Soc, Perkin Trans. 1:2363–2366. 1984. View Article : Google Scholar
20	Santos HS, Barros FW, Albuquerque MR, Bandeira PN, Pessoa C, Braz-Filho R, Monte FJ, Leal-Cardoso JH and Lemos TL: Cytotoxic diterpenoids from Croton argyrophylloides. J Nat Prod. 72:1884–1887. 2009. View Article : Google Scholar : PubMed/NCBI
21	Ye Q, Yao G, Zhang M, Guo G, Hu Y, Jiang J, Cheng L, Shi J, Li H, Zhang Y and Liu H: A novel ent-kaurane diterpenoid executes antitumor function in colorectal cancer cells by inhibiting Wnt/β-catenin signaling. Carcinogenesis. 36:318–326. 2015. View Article : Google Scholar : PubMed/NCBI
22	Li X, Pu J, Jiang S, Su J, Kong L, Mao B, Sun H and Li Y: Henryin, an ent-kaurane diterpenoid, inhibits Wnt signaling through interference with β-catenin/TCF4 interaction in colorectal cancer cells. PLoS One. 8:e685252013. View Article : Google Scholar : PubMed/NCBI
23	Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X and He X: Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 108:837–847. 2002. View Article : Google Scholar : PubMed/NCBI
24	Jin Y, Kanno T and Nishizaki T: Acute restraint stress impairs induction of long-term potentiation by activating GSK-3β. Neurochem Res. 40:36–40. 2015. View Article : Google Scholar : PubMed/NCBI
25	Aschenbach WG, Ho RC, Sakamoto K, Fujii N, Li Y, Kim YB, Hirshman MF and Goodyear LJ: Regulation of dishevelled and beta-catenin in rat skeletal muscle: An alternative exercise-induced GSK-3beta signaling pathway. Am J Physiol Endocrinol Metab. 291:E152–E158. 2006. View Article : Google Scholar : PubMed/NCBI
26	Kim S, Lee J, Park J and Chung J: BP75, bromodomain-containing M(r) 75,000 protein, binds dishevelled-1 and enhances Wnt signaling by inactivating glycogen synthase kinase-3 beta. Cancer Res. 63:4792–4795. 2003.PubMed/NCBI
27	Gao C and Chen YG: Dishevelled: The hub of Wnt signaling. Cell Signal. 22:717–727. 2010. View Article : Google Scholar : PubMed/NCBI
28	Liao YJ, Bai HY, Li ZH, Zou J, Chen JW, Zheng F, Zhang JX, Mai SJ, Zeng MS, Sun HD, et al: Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells. Cell Death Dis. 5:e11372014. View Article : Google Scholar : PubMed/NCBI
29	Weng W, Feng J, Qin H and Ma Y: Molecular therapy of colorectal cancer: Progress and future directions. Int J Cancer. 136:493–502. 2015.PubMed/NCBI
30	Zhang X and Hao J: Development of anticancer agents targeting the Wnt/β-catenin signaling. Am J Cancer Res. 5:2344–2360. 2015.PubMed/NCBI
31	Bi X, Xia X, Mou T, Jiang B, Fan D, Wang P, Liu Y, Hou Y and Zhao Y: Anti-tumor activity of three ginsenoside derivatives in lung cancer is associated with Wnt/β-catenin signaling inhibition. Eur J Pharmacol. 742:145–152. 2014. View Article : Google Scholar : PubMed/NCBI
32	Albring KF, Weidemuller J, Mittag S, Weiske J, Friedrich K, Geroni MC, Lombardi P and Huber O: Berberine acts as a natural inhibitor of Wnt/β-catenin signaling-identification of more active 13-arylalkyl derivatives. Biofactors. 39:652–662. 2013. View Article : Google Scholar : PubMed/NCBI
33	Lee MA, Kim WK, Park HJ, Kang SS and Lee SK: Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with the suppression of Wnt/β-catenin signaling pathway in colon cancer cells. Bioorg Med Chem Lett. 23:5511–5514. 2013. View Article : Google Scholar : PubMed/NCBI
34	Choi H, Gwak J, Cho M, Ryu MJ, Lee JH, Kim SK, Kim YH, Lee GW, Yun MY, Cuong NM, et al: Murrayafoline A attenuates the Wnt/beta-catenin pathway by promoting the degradation of intracellular beta-catenin proteins. Biochem Biophys Res Commun. 391:915–920. 2010. View Article : Google Scholar : PubMed/NCBI
35	Tarapore RS, Siddiqui IA and Mukhtar H: Modulation of Wnt/β-catenin signaling pathway by bioactive food components. Carcinogenesis. 33:483–491. 2012. View Article : Google Scholar : PubMed/NCBI
36	Bai L and Wang S: Targeting apoptosis pathways for new cancer therapeutics. Annu Rev Med. 65:139–155. 2014. View Article : Google Scholar : PubMed/NCBI
37	Sun SY, Hail N Jr and Lotan R: Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 96:662–672. 2004. View Article : Google Scholar : PubMed/NCBI
38	Kucharczak J, Simmons MJ, Fan Y and Gelinas C: To be, or not to be: NF-kappaB is the answer-role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene. 22:8961–8982. 2003. View Article : Google Scholar : PubMed/NCBI
39	Lin A and Karin M: NF-kappaB in cancer: A marked target. Semin Cancer Biol. 13:107–114. 2003. View Article : Google Scholar : PubMed/NCBI
40	Li XL, Zhou J, Chen ZR and Chng WJ: P53 mutations in colorectal cancer-molecular pathogenesis and pharmacological reactivation. World J Gastroenterol. 21:84–93. 2015. View Article : Google Scholar : PubMed/NCBI
41	Dashzeveg N and Yoshida K: Cell death decision by p53 via control of the mitochondrial membrane. Cancer Lett. 367:108–112. 2015. View Article : Google Scholar : PubMed/NCBI
42	Wang J and Yi J: Cancer cell killing via ROS: To increase or decrease, that is the question. Cancer Biol Ther. 7:1875–1884. 2008. View Article : Google Scholar : PubMed/NCBI