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Open AccessArticle

Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells

1
Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
2
Department of Family Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
3
Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan
4
Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
5
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
6
Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 184; https://doi.org/10.3390/biom10020184
Received: 4 December 2019 / Revised: 23 January 2020 / Accepted: 23 January 2020 / Published: 25 January 2020
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natural products may be a solution. Asiatic acid (AA), extracted from Centella asiatica, was found to have anticancer activity in various cancers. The aim of this study is to examine the cytotoxic effect and mediated mechanism of AA in cisplatin-resistant NPC cells. The results shows that AA significantly reduce the cell viability of cisplatin-resistant NPC cell lines (cis NPC-039 and cis NPC-BM) in dose and time dependent manners caused by apoptosis through the both intrinsic and extrinsic apoptotic pathways, including altered mitochondrial membrane potential, activated death receptors, increased Bax expression, and upregulated caspase 3, 8, and 9. The Western blot analysis of AA-treated cell lines reveals that the phosphorylation of MAPK pathway proteins is involved. Further, the results of adding inhibitors of these proteins indicates that the phosphorylation of p38 are the key mediators in AA-induced apoptosis in cisplatin-resistant human NPC cells. This is the first study to demonstrate the AA-induced apoptotic pathway through the phosphorylation p38 in human cisplatin-resistant nasopharyngeal carcinoma. AA is expected to be another therapeutic option for cisplatin-resistant NPC because of the promising anti-cancer effect and fewer toxic properties. View Full-Text
Keywords: Asiatic acid; nasopharyngeal cancer; apoptosis; cisplatin resistance; MAPK pathway Asiatic acid; nasopharyngeal cancer; apoptosis; cisplatin resistance; MAPK pathway
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MDPI and ACS Style

Liu, Y.-T.; Chuang, Y.-C.; Lo, Y.-S.; Lin, C.-C.; Hsi, Y.-T.; Hsieh, M.-J.; Chen, M.-K. Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells. Biomolecules 2020, 10, 184.

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