1,6‑Bis[4‑(4‑amino‑3‑hydroxyphenoxy)phenyl] diamantane potentiates in vitro and in vivo antitumor effects of irinotecan on human colorectal cancer cells

Yang,Po‑Sheng; Wang,Jane‑Jen; Wang,Yea‑Hwey; Jan,Woan‑Ching; Cheng,Shih‑Ping; Hsu,Yi‑Chiung

doi:10.3892/ol.2016.4430

May-2016 Volume 11 Issue 5

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May-2016 Volume 11 Issue 5

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Article

1,6‑Bis[4‑(4‑amino‑3‑hydroxyphenoxy)phenyl] diamantane potentiates in vitro and in vivo antitumor effects of irinotecan on human colorectal cancer cells

Authors:
- Po‑Sheng Yang
- Jane‑Jen Wang
- Yea‑Hwey Wang
- Woan‑Ching Jan
- Shih‑Ping Cheng
- Yi‑Chiung Hsu
View Affiliations / Copyright

Affiliations: Department of Surgery, Mackay Memorial Hospital, Taipei 10449, Taiwan R.O.C., Department of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan R.O.C., Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan R.O.C., Institute of Statistical Science, Academia Sinica, Taipei 11529, Taiwan R.O.C.
Pages: 3551-3557
|
Published online on: April 7, 2016

https://doi.org/10.3892/ol.2016.4430
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Abstract

1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD), a diamantane derivative, was previously noted as an anticancer compound through anticancer drug screening with NCI‑60 human tumor cells. Irinotecan (CPT‑11), a semisynthetic derivative of camptothecin, is clinically active in the treatment of colorectal cancer, with no cross‑resistance. The current study conducted a pharmacokinetic evaluation of DPD, an essential component of drug discovery. Subsequent pathway analysis of microarray gene expression data indicated that the anticancer mechanisms of DPD were associated with cell cycle progression and apoptosis. The combined effect of DPD and CPT‑11 with regard to the mechanisms of apoptosis‑related pathways in COLO 205 cells, and the antitumor effects in colon cancer xenograft mice, were investigated. The plasma concentration and pharmacokinetic parameters of DPD in male albino rats were analyzed following a single dose of DPD by injection. The protein expression of active caspase‑3, procaspase‑3 and poly ADP‑ribose polymerase (PARP) in COLO 205 cells treated with DPD and CPT‑11, alone or combined, was evaluated by western blotting. A trypan blue dye exclusion assay revealed that, whilst DPD alone demonstrated good antitumor effects, this effect was potentiated when combined with CPT‑11. Combined treatment with DPD and CPT‑11 upregulated the expression of cleaved PARP, procaspase‑3, caspase‑3 and active caspase‑3 in COLO 205 cells. In the colon cancer xenograft model, compared with the control (vehicle‑treated) mice, the sizes of the tumors were significantly lower in mice treated with DPD and CPT‑11, alone or in combination. Thus, DPD may be a potential therapeutic agent for the treatment of colorectal cancer via upregulating apoptosis‑related pathways.

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1	Byeon JS, Yang SK, Kim TI, Kim WH, Lau JY, Leung WK, Fujita R, Makharia GK, Abdullah M, Hilmi I, et al: Colorectal neoplasm in asymptomatic Asians: A prospective multinational multicenter colonoscopy survey. Gastrointest Endosc. 65:1015–1022. 2007. View Article : Google Scholar : PubMed/NCBI
2	Pham NM, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Nagata C, Inoue M, Tsugane S, et al: Meat consumption and colorectal cancer risk: An evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 44:641–650. 2014. View Article : Google Scholar : PubMed/NCBI
3	Wasserman E, Myara A, Lokiec F, Goldwasser F, Trivin F, Mahjoubi M, Misset JL and Cvitkovic E: Severe CPT-11 toxicity in patients with Gilbert's syndrome: Two case reports. Ann Oncol. 8:1049–1051. 1997. View Article : Google Scholar : PubMed/NCBI
4	Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, et al: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J Clin Oncol. 26:2013–2019. 2008. View Article : Google Scholar : PubMed/NCBI
5	Aggarwal BB, Takada Y and Oommen OV: From chemoprevention to chemotherapy: Common targets and common goals. Expert Opin Investig Drugs. 13:1327–1338. 2004. View Article : Google Scholar : PubMed/NCBI
6	Robert J and Rivory L: Pharmacology of irinotecan. Drugs Today (Barc). 34:777–803. 1998. View Article : Google Scholar : PubMed/NCBI
7	Kawato Y, Furuta T, Aonuma M, Yasuoka M, Yokokura T and Matsumoto K: Antitumor activity of a camptothecin derivative, CPT-11, against human tumor xenografts in nude mice. Cancer Chemother Pharmacol. 28:192–198. 1991. View Article : Google Scholar : PubMed/NCBI
8	Houghton PJ, Cheshire PJ, Hallman JD II, Lutz L, Friedman HS, Danks MK and Houghton JA: Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol. 36:393–403. 1995. View Article : Google Scholar : PubMed/NCBI
9	Karato A, Sasaki Y, Shinkai T, Eguchi K, Tamura T, Ohe Y, Oshita F, Nishio M, Kunikane H, Arioka H, et al: Phase I study of CPT-11 and etoposide in patients with refractory solid tumors. J Clin Oncol. 11:2030–2035. 1993.PubMed/NCBI
10	Armand JP, Terret C, Couteau C and Rixe O: CPT-11. The European experience. Ann NY Acad Sci. 803:282–291. 1996. View Article : Google Scholar : PubMed/NCBI
11	Rothenberg ML: Irinotecan (CPT-11): Recent developments and future directions - colorectal cancer and beyond. Oncologist. 6:66–80. 2001. View Article : Google Scholar : PubMed/NCBI
12	Gamelin E, Gamelin L, Bossi L and Quasthoff S: Clinical aspects and molecular basis of oxaliplatin neurotoxicity: Current management and development of preventive measures. Semin Oncol. 29(5 Suppl 15): 21–33. 2002. View Article : Google Scholar : PubMed/NCBI
13	Hecht JR: Gastrointestinal toxicity or irinotecan. Oncology (Williston Park). 12(8 Suppl 6): 72–78. 1998.PubMed/NCBI
14	Chen CSH, Shen DM and Wentzek SE: Preparation of adamantane and diamantane derivatives as antivirals. Patent WO 9428885 Al. 1994.
15	Chen CSHSD and Wentzek SE: Preparation of adamantane and diamantane derivatives as antivirals. WO 9428885 Al (patent). 1994.
16	Wang JJ, Huang KT and Chern YT: Induction of growth inhibition and G1 arrest in human cancer cell lines by relatively low-toxic diamantane derivatives. Anticancer Drugs. 15:277–286. 2004. View Article : Google Scholar : PubMed/NCBI
17	Wang JJ, Chang YF, Chern YT and Chi CW: Study of in vitro and in vivo effects of 1,6-Bis [4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD), a novel cytostatic and differentiation inducing agent, on human colon cancer cells. Br J Cancer. 89:1995–2003. 2003. View Article : Google Scholar : PubMed/NCBI
18	Chang YF, Chi CW, Chern YT and Wang JJ: Effects of 1,6-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] diamantane (DPD), a reactive oxygen species and apoptosis inducing agent, on human leukemia cells in vitro and in vivo. Toxicol Appl Pharmacol. 202:1–12. 2005. View Article : Google Scholar : PubMed/NCBI
19	National Research Council: Guide for the Care and Use of Laboratory Animals (8th). The National Academies Press. Washington, DC: 2011.
20	Holbeck SL, Collins JM and Doroshow JH: Analysis of food and drug administration-approved anticancer agents in the NCI60 panel of human tumor cell lines. Mol Cancer Ther. 9:1451–1460. 2010. View Article : Google Scholar : PubMed/NCBI
21	United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) Guidelines for the Welfare of Animals in Experimental Neoplasia (Second Edition). Br J Cancer. 77:1–10. 1998. View Article : Google Scholar
22	Attia MA and Weiss DW: Immunology of spontaneous mammary carcinomas in mice. V. Acquired tumor resistance and enhancement in strain A mice infected with mammary tumor virus. Cancer Res. 26:1787–1800. 1966.PubMed/NCBI
23	Wang JJ, Lee JY, Chen YC, Chern YT and Chi CW: The antitumor effect of a novel differentiation inducer, 2,2-Bis (4-(4-amino-3-hydroxyphenoxy) phenyl) adamantane (DPA), in combinatory therapy on human colon cancer. Int J Oncol. 28:1003–1012. 2006.PubMed/NCBI
24	Singh RP, Dhanalakshmi S and Agarwal R: Phytochemicals as cell cycle modulators-a less toxic approach in halting human cancers. Cell Cycle. 1:156–161. 2002. View Article : Google Scholar : PubMed/NCBI
25	Kaufmann SH and Earnshaw WC: Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 256:42–49. 2000. View Article : Google Scholar : PubMed/NCBI
26	Makin G and Hickman JA: Apoptosis and cancer chemotherapy. Cell Tissue Res. 301:143–152. 2000. View Article : Google Scholar : PubMed/NCBI
27	Cotter TG: Apoptosis and cancer: The genesis of a research field. Nat Rev Cancer. 9:501–507. 2009. View Article : Google Scholar : PubMed/NCBI
28	Wang R, Ma L, Weng D, Yao J, Liu X and Jin F: Gallic acid induces apoptosis and enhances the anticancer effects of cisplatin in human small cell lung cancer H446 cell line via the ROS-dependent mitochondrial apoptotic pathway. Oncol Rep. Mar 17–2016.(Epub ahead of print). View Article : Google Scholar
29	Khuda-Bukhsh AR, Das S and Saha SK: Molecular approaches toward targeted cancer prevention with some food plants and their products: Inflammatory and other signal pathways. Nutr Cancer. 66:194–205. 2014. View Article : Google Scholar : PubMed/NCBI
30	Zhang L and Yu J: Role of apoptosis in colon cancer biology, therapy, and prevention. Curr Colorectal Cancer Rep. 9:2013. View Article : Google Scholar
31	Lavrik IN, Golks A and Krammer PH: Caspases: Pharmacological manipulation of cell death. J Clin Invest. 115:2665–2672. 2005. View Article : Google Scholar : PubMed/NCBI
32	Woo M, Hakem R, Soengas MS, Duncan GS, Shahinian A, Kägi D, Hakem A, McCurrach M, Khoo W, Kaufman SA, et al: Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev. 12:806–819. 1998. View Article : Google Scholar : PubMed/NCBI
33	Slee EA, Adrain C and Martin SJ: Executioner caspase-3, −6, and −7 perform distinct, non-redundant roles during the demolition phase of apoptosis. J Biol Chem. 276:7320–7326. 2001. View Article : Google Scholar : PubMed/NCBI
34	Looi CY, Arya A, Cheah FK, et al: Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds. PloS One. 8:e566432013. View Article : Google Scholar : PubMed/NCBI
35	Lin Y, Bai L, Chen W and Xu S: The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert Opin Ther Targets. 14:45–55. 2010. View Article : Google Scholar : PubMed/NCBI
36	Zhou S, Li N, Wang X, et al: In vitro cytotoxicity, pharmacokinetics and tissue distribution in rats of MXN-004, a novel conjugate of polyethylene glycol and SN38. Xenobiotica. 44:562–569. 2014. View Article : Google Scholar : PubMed/NCBI