Systemic and local injections of lupeol inhibit tumor growth in a melanoma‑bearing mouse model

Nitta,Makiko; Azuma,Kazuo; Hata,Keishi; Takahashi,Saori; Ogiwara,Kikumi; Tsuka,Takeshi; Imagawa,Tomohiro; Yokoe,Inoru; Osaki,Tomohiro; Minami,Saburo; Okamoto,Yoshiharu

doi:10.3892/br.2013.116

July-August 2013 Volume 1 Issue 4

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.

July-August 2013 Volume 1 Issue 4

Full Size Image

Article

Systemic and local injections of lupeol inhibit tumor growth in a melanoma‑bearing mouse model

Authors:
- Makiko Nitta
- Kazuo Azuma
- Keishi Hata
- Saori Takahashi
- Kikumi Ogiwara
- Takeshi Tsuka
- Tomohiro Imagawa
- Inoru Yokoe
- Tomohiro Osaki
- Saburo Minami
- Yoshiharu Okamoto
View Affiliations / Copyright

Affiliations: Faculty of Agriculture, Tottori University, Tottori, Tottori 6808553, Japan, Institute for Food and Brewing, Akita Prefectural Agricultural, Forestry and Fisheries Research Center, Akita, Akita 0101623, Japan, Laboratory of Veterinary Pathology, Azabu University, Sagamihara, Kanagawa 2525201, Japan
Pages: 641-645
|
Published online on: May 28, 2013

https://doi.org/10.3892/br.2013.116
Expand metrics +

Abstract

Melanoma is the most aggressive type of skin cancer and it is procured from activated or genetically altered epidermal melanocytes. In the present study, the tumor‑suppressive effects of systemic and local injections of lupeol, a triterpene extracted from Indian lettuce (Lactuca indica), in a melanoma‑bearing mouse model were evaluated. Mice were injected once with lupeol or olive oil (solvent control) subcutaneously into the skin of the back or into the tumor tissue. seven days after the injection, the tumor growth rates were calculated and the tumor tissues were collected. Immunohistochemical staining for Ki‑67 and proliferating cell nuclear antigen (PCNA) were performed. the tumor growth rates in the lupeol‑injected group were significantly decreased compared to those observed in the non‑treated (NT) and solvent control groups. Lupeol also significantly decreased the areas positively stained for Ki‑67 and PCNA in the tumor tissues compared to those in the NT and solvent control groups. The results of the present study demonstrated that systemic and local injections of lupeol suppress tumor growth and induce cell cycle arrest in a melanoma‑bearing mouse model. These data suggest that lupeol may be effective as a novel therapeutic option for melanoma patients.

View Figures

View References

1	Oliveria S, Dusza S and Berwick M: Issues in the epidemiology of melanoma. Expert Rev Anticancer Ther. 1:453–459. 2001. View Article : Google Scholar : PubMed/NCBI
2	Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, et al: Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 26:527–534. 2008. View Article : Google Scholar : PubMed/NCBI
3	Bergman PJ: Canine oral melanoma. Clin Tech Small Anim Pract. 22:55–60. 2007. View Article : Google Scholar
4	Saleem M, Kaur S, Kweon MH, Adhami VM, Afaq F and Mukhtar H: Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway. Carcinogenesis. 26:1956–1964. 2005. View Article : Google Scholar
5	Geetha T and Varalakshmi P: Anti-inflammatory activity of lupeol and lupeol linoleate in rats. J Ethnopharmacol. 76:77–80. 2001. View Article : Google Scholar : PubMed/NCBI
6	Prasad S, Kalra N and Shukla Y: Hepatoprotective effects of lupeol and mango pulp extract of carcinogen induced alteration in Swiss albino mice. Mol Nutr Food Res. 51:352–359. 2007. View Article : Google Scholar : PubMed/NCBI
7	Chaturvedi PK, Bhui K and Shukla Y: Lupeol: connotations for chemoprevention. Cancer Lett. 263:1–13. 2008. View Article : Google Scholar : PubMed/NCBI
8	Saleem M: Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene. Cancer Lett. 285:109–115. 2009. View Article : Google Scholar : PubMed/NCBI
9	Hata K, Ishikawa K, Hori K and Konishi T: Differentiation-inducing activity of lupeol, a lupane-type triterpene from Chinese dandelion root (Hokouei-kon), on a mouse melanoma cell line. Biol Pharm Bull. 23:962–967. 2000. View Article : Google Scholar : PubMed/NCBI
10	Hata K, Mukaiyama T, Tsujimura N, Sato Y, Kosaka Y, Sakamoto K and Hori K: Differentiation-inducing activity of lupane triterpenes on a mouse melanoma cell line. Cytotechnology. 52:151–158. 2006. View Article : Google Scholar : PubMed/NCBI
11	Saleem M, Maddodi N, Abu Zaid M, Khan N, bin Hafeez B, Asim M, Suh Y, Yun JM, Setaluri V and Mukhtar H: Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. Clin Cancer Res. 14:2119–2127. 2008. View Article : Google Scholar : PubMed/NCBI
12	Hata K, Hori K and Takahashi S: Role of p38 MAPK in lupeol-induced B16 2F2 mouse melanoma cell differentiation. J Biochem. 134:441–445. 2003. View Article : Google Scholar : PubMed/NCBI
13	You YJ, Nam NH, Kim Y, Bae KH and Ahn BZ: Antiangiogenic activity of lupeol from Bombax ceiba. Phytother Res. 17:341–344. 2003. View Article : Google Scholar : PubMed/NCBI
14	Hata K, Hori K, Murata J and Takahashi S: Remodeling of actin cytoskeleton in lupeol-induced B16 2F2 cell differentiation. J Biochem. 138:467–472. 2005. View Article : Google Scholar : PubMed/NCBI
15	Ogiwara K and Hata K: Melanoma cell differentiation induced by lupeol separates into two stages: morphological and functional changes. J Nat Med. 63:323–326. 2009. View Article : Google Scholar : PubMed/NCBI
16	Hata K, Hori K, Mukaiyama T, Sakamoto K and Takahashi S: Activators of melanin biosynthesis from Lactuca indica. Nat Med. 57:238–241. 2003.
17	Brown DC and Gatter KC: Ki67 protein: the immaculate deception? Histopathology. 40:2–11. 2002. View Article : Google Scholar
18	Lopez F, Belloc F, Lacombe F, Dumain P, Reiffers J, Bernard P and Boisseau MR: Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes. Cytometry. 12:42–49. 1991. View Article : Google Scholar : PubMed/NCBI
19	Moldovan GL, Pfander B and Jentsch S: PCNA, the maestro of the replication fork. Cell. 129:665–679. 2007. View Article : Google Scholar : PubMed/NCBI
20	Gould Rothberg BE, Bracken MB and Rimm DL: Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 101:452–474. 2009.PubMed/NCBI
21	Lee B, Mukhi N and Liu D: Current management and novel agents for malignant melanoma. J Hematol Oncol. 5:32012. View Article : Google Scholar : PubMed/NCBI
22	Garbe C, Eigentler TK, Keilholz U, Hauschild A and Kirkwood JM: Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist. 16:5–24. 2011. View Article : Google Scholar : PubMed/NCBI

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

Systemic and local injections of lupeol inhibit tumor growth in a melanoma‑bearing mouse model

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Related Articles