Carnosic acid impedes cell growth and enhances anticancer effects of carmustine and lomustine in melanoma

Author:

Lin Kun-I12,Lin Chih-Chien1,Kuo Shyh-Ming3,Lai Jui-Chi4,Wang You-Qi4,You Huey-Ling56,Hsu Mei-Ling5,Chen Chang-Han7,Shiu Li-Yen89

Affiliation:

1. Department of Cosmetic Science, Providence University, Taichung, Taiwan, R.O.C

2. Departments of Obstetrics and Gynecology, Chang Bing Show Chwan Memorial Hospital, Lukang Zhen, Changhua County, Taiwan, R.O.C

3. Department of Biomedical Engineering, I-Shou University, Taiwan, R.O.C

4. Department of Biological Science and Technology, I-SHOU University, Kaohsiung, Taiwan, R.O.C

5. Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, R.O.C

6. Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan, R.O.C

7. Guangdong Institution of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China

8. Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, R.O.C

9. Cell Therapy and Research Center, Department of Medical Research, E-Da Cancer Hospital, Kaohsiung, Taiwan, R.O.C

Abstract

Carnosic acid (CA), a major polyphenolic diterpene present in Rosmarinus officinalis, has been reported to have multiple functions, including antitumor activity. The MTT assay, BrdU incorporation, wound healing, and colony formation were used to detect melanoma B16F10 cell growth and proliferation. Flow cytometry was used for cell cycle detection. p21 and p27 expression was detected by Western blotting. B16F10 cell xenograft model was established, and treated with CA, carmustine (BCNU), or lomustine (CCNU). The present study found that CA exhibits significant growth inhibition and cell cycle arrest in melanoma B16F10 cells. We also found that CA triggers cell cycle arrest at G0/G1 phase, and enhances p21 expression. Additionally, CA can enhance BCNU- and CCNU-mediated cytotoxicity and cell cycle arrest in B16F10 cells. Finally, we found that CA inhibits tumor growth, and reduces the values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in vivo. The present study study concluded that CA may be safe and useful as a novel chemotherapeutic agent.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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