Da Jeong Kim1, Ji Hye Lee1, Hae Ryoun Park2, Young Whan Choi3. 1. Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, South Korea; School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea. 2. Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, South Korea; School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea; Institute of Translational Dental Sciences, Pusan National University, 49 Busandaehak-Ro, Yangsan 626-870, South Korea. Electronic address: parkhr@pusan.ac.kr. 3. Department of Horticultural Bioscience, Pusan National University, Samnangjin-Ro 1268-50, Samnangjin-eup, Miryang 627-706, South Korea. Electronic address: ywchoi@pusan.ac.kr.
Abstract
OBJECTIVES: Recently, shikonin derivatives from Lithospermum erythrorhizon have been suggested as potential chemotherapeutic agents against numerous types of cancers in addition to their traditional uses, e.g., as anti-inflammatory agents. Acetylshikonin, one of shikonin derivatives, has also been reported to possess anticancer activity. However, few studies of the effectiveness of acetylshikonin against cancer cells have been conducted, and there are no studies of oral cancers. In this study, we investigated the usefulness of acetylshikonin as a treatment regimen for oral cancers by observing the growth inhibitory function of acetylshikonin and the involved mechanisms. DESIGNS: The viability, cell cycle, and ratio of apoptotic cells of oral squamous cell carcinoma (OSCC) cells were observed after treatment with acetylshikonin using MTT assay, flow cytometric analysis, and Annexin V/PI staining, respectively. In addition, molecular changes of apoptosis-related pathways and the role of reactive oxygen species (ROS) were analyzed in acetylshikonin-treated cells. RESULTS: We observed that acetylshikonin significantly suppressed the growth of OSCC cells by inducing apoptotic cell death, and acetylshikonin affected the viability of a normal keratinocyte cell line HaCaT to a lesser degree, suggesting that acetylshikonin may be a good chemotherapeutic reagent with less toxicity to normal tissues. In addition, we found that acetylshikonin-induced apoptosis of OSCC cells is mediated by ROS as well as G2 cell cycle arrest. ROS production in response to acetylshikonin treatment enhanced the phosphorylation of JNK and p38 MAPK, which are in the major pathways of apoptotic cell death mechanisms. CONCLUSIONS: In summary, our data suggest that acetylshikonin is a strong candidate for use as a selective chemotherapeutic agent for the treatment of OSCC.
OBJECTIVES: Recently, shikonin derivatives from Lithospermum erythrorhizon have been suggested as potential chemotherapeutic agents against numerous types of cancers in addition to their traditional uses, e.g., as anti-inflammatory agents. Acetylshikonin, one of shikonin derivatives, has also been reported to possess anticancer activity. However, few studies of the effectiveness of acetylshikonin against cancer cells have been conducted, and there are no studies of oral cancers. In this study, we investigated the usefulness of acetylshikonin as a treatment regimen for oral cancers by observing the growth inhibitory function of acetylshikonin and the involved mechanisms. DESIGNS: The viability, cell cycle, and ratio of apoptotic cells of oral squamous cell carcinoma (OSCC) cells were observed after treatment with acetylshikonin using MTT assay, flow cytometric analysis, and Annexin V/PI staining, respectively. In addition, molecular changes of apoptosis-related pathways and the role of reactive oxygen species (ROS) were analyzed in acetylshikonin-treated cells. RESULTS: We observed that acetylshikonin significantly suppressed the growth of OSCC cells by inducing apoptotic cell death, and acetylshikonin affected the viability of a normal keratinocyte cell line HaCaT to a lesser degree, suggesting that acetylshikonin may be a good chemotherapeutic reagent with less toxicity to normal tissues. In addition, we found that acetylshikonin-induced apoptosis of OSCC cells is mediated by ROS as well as G2 cell cycle arrest. ROS production in response to acetylshikonin treatment enhanced the phosphorylation of JNK and p38 MAPK, which are in the major pathways of apoptotic cell death mechanisms. CONCLUSIONS: In summary, our data suggest that acetylshikonin is a strong candidate for use as a selective chemotherapeutic agent for the treatment of OSCC.
Authors: Bong-Hae Cho; Yun-Hoa Jung; Da Jeong Kim; Bok Hee Woo; Ji Eun Jung; Ji Hye Lee; Young Whan Choi; Hae Ryoun Park Journal: Mol Med Rep Date: 2017-11-24 Impact factor: 2.952