Combined effect of papuamine and doxorubicin in human breast cancer MCF‑7 cells

Kanno,Syu‑Ichi; Yomogida,Shin; Tomizawa,Ayako; Yamazaki,Hiroyuki; Ukai,Kazuyo; Mangindaan,Remy   E.P.; Namikoshi,Michio; Ishikawa,Masaaki

doi:10.3892/ol.2014.2218

August-2014 Volume 8 Issue 2

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

August-2014 Volume 8 Issue 2

Full Size Image

Article Open Access

Combined effect of papuamine and doxorubicin in human breast cancer MCF‑7 cells

Authors:
- Syu‑Ichi Kanno
- Shin Yomogida
- Ayako Tomizawa
- Hiroyuki Yamazaki
- Kazuyo Ukai
- Remy E.P. Mangindaan
- Michio Namikoshi
- Masaaki Ishikawa
View Affiliations / Copyright

Affiliations: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, Sendai 981‑8558, Japan, Department of Natural Product Chemistry, Tohoku Pharmaceutical University, Sendai 981‑8558, Japan, Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia
Pages: 547-550
|
Published online on: June 3, 2014

https://doi.org/10.3892/ol.2014.2218
Expand metrics +

Abstract

Our previous study reported that an extract of an Indonesian marine sponge, Haliclona sp., showed potent cytotoxicity and induced apoptosis. The major cytotoxic chemical compound was identified as papuamine, which caused reduction of cell survival through activation of c‑Jun N‑terminal kinase (JNK) in human breast cancer MCF‑7 cells. Doxorubicin (DOX), a Streptomyces metabolite, is used in chemotherapy against a wide range of cancers, including breast cancer. The present study examined the combined effect of papuamine and DOX on MCF‑7 cells. The effect of these reagents on cell growth was assessed by a colony formation assay. Incubation with either of the reagents alone resulted in concentration‑dependent decreases in the colony formation of the MCF‑7 cells. Incubation with the reagents together at sub‑cytotoxic concentrations resulted in significant decreases in colony formation. The phosphorylation of JNK, the activated form of the protein, was elevated in a concentration‑dependent manner upon co‑incubation with papuamine and DOX. Fluorescence intensity analysis demonstrated that papuamine caused a small, but non‑significant, decrease in cellular accumulation of DOX. These results indicate that the combinatory effect of papuamine and DOX is not associated with changes in the cellular accumulation of DOX, and may instead reflect additive effects on JNK activation. This study indicates that papuamine may represent a novel type of modulator for DOX chemotherapy.

View Figures

View References

1	Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F and Capocaccia R; EUROCARE Working Group. EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999 Results and commentary. Eur J Cancer. 45:931–991. 2009.
2	Smith LA, Cornelius VR, Plummer CJ, et al: Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 10:3372010.
3	Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004.
4	Gewirtz DA: A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 57:727–741. 1999.
5	Kim J and Freeman MR: JNK/SAPK mediates doxorubicin-induced differentiation and apoptosis in MCF-7 breast cancer cells. Breast Cancer Res Treat. 79:321–328. 2003.
6	Li F, Meng L, Xing H, et al: Essential role of c-Jun-NH2-terminal kinase on synergy induction of apoptosis by TRAIL plus ADM in ADM resistant MCF-7/ADM cells. Apoptosis. 11:1239–1246. 2006.
7	Mansouri A, Ridgway LD, Korapati AL, et al: Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. J Biol Chem. 278:19245–19256. 2003.
8	Yamazaki H, Wewengkang DS, Kanno S, et al: Papuamine and haliclonadiamine, obtained from an Indonesian sponge Haliclona sp, inhibited cell proliferation of human cancer cell lines. Nat Prod Res. 27:1012–1015. 2013.
9	Kanno S, Yomogida S, Tomizawa A, et al: Papuamine causes autophagy following the reduction of cell survival through mitochondrial damage and JNK activation in MCF-7 human breast cancer cells. Int J Oncol. 43:1413–1419. 2013.
10	Hanauske AR, Hanauske U and Von Hoff DD: The human tumor cloning assay in cancer research and therapy: a review with clinical correlations. Curr Probl Cancer. 9:1–66. 1985.
11	Slee PH, Van Oosterom AT and De Bruijn EA: Predictive testing in cancer chemotherapy. II. In vitro. Pharm Weekbl Sci. 7:125–133. 1985.
12	Shoemaker RH, Wolpert-DeFilippes MK, Kern DH, et al: Application of a human tumor colony-forming assay to new drug screening. Cancer Res. 45:2145–2153. 1985.
13	Freedman VH and Shin SI: Cellular tumorigenicity in nude mice: correlation with cell growth in semi-solid medium. Cell. 3:355–359. 1974.
14	Panaretakis T, Laane E, Pokrovskaja K, et al: Doxorubicin requires the sequential activation of caspase-2, protein kinase Cdelta, and c-Jun NH2-terminal kinase to induce apoptosis. Mol Biol Cell. 16:3821–3831. 2005.
15	Ferry DR: Testing the role of P-glycoprotein expression in clinical trials: applying pharmacological principles and best methods for detection together with good clinical trials methodology. Int J Clin Pharmacol Ther. 36:29–40. 1998.
16	Robert J and Jarry C: Multidrug resistance reversal agents. J Med Chem. 46:4805–4817. 2003.
17	Sikic BI, Fisher GA, Lum BL, Halsey J, Beketic-Oreskovic L and Chen G: Modulation and prevention of multidrug resistance by inhibitors of P-glycoprotein. Cancer Chemother Pharmaco. 40(Suppl): S13–S19. 1997.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Combined effect of papuamine and doxorubicin in human breast cancer MCF‑7 cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles