Yoon Heein, Park Junhee, Park Kwang-Kyun, Kim Jin, Bandara N Champika, Bandara B M R, Tilakaratne Wanninayake M, Chung Won-Yoon
Department of Applied Life Science, The Graduate School, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Department of Oral Biology, Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Evid Based Complement Alternat Med. 2017;2017:7272947. doi: 10.1155/2017/7272947. Epub 2017 Nov 22.
Oral squamous cell carcinoma (OSCC) frequently invades mandibular bone, and outcomes for treatment with surgical resection are typically poor, ultimately resulting in death. L. (Apocynaceae), distributed throughout Sri Lanka and India, has been used as a folk remedy to treat various diseases. Treatment with methanol extract of bark (HABE) inhibited cell viability and BrdU incorporation and induced apoptotic cell death in Ca9-22 gingival and HSC-3 tongue SCC cells. Flow cytometric analysis indicated that HABE treatment preferentially induces apoptotic cell death via increasing the sub-G1 peak in Ca9-22 cells and cell cycle arrest at the G1 phase in HSC-3 cells. HABE treatment in the presence of zVAD-fmk, a pan-caspase inhibitor, rescued cell viabilities in both OSCC cell lines. The ratio of Bax to Bcl-2 increased with reductions in the Bcl-2 protein expression, and the activation of caspase 3 and subsequent cleavage of PARP was detected in HABE-treated Ca9-22 and HSC-3 cells. Furthermore, HABE treatment at noncytotoxic concentrations inhibited osteoclast formation in RANKL-stimulated bone marrow macrophages. Taken together, HABE possesses the inhibitory activity on the growth of OSCC cells and antiosteoclastogenic activity. Therefore, HABE may be a promising alternative and complementary agent for preventing and treating OSCC.
口腔鳞状细胞癌（OSCC）常侵犯下颌骨，手术切除治疗的效果通常较差，最终导致死亡。萝芙木（夹竹桃科）分布于斯里兰卡和印度各地，一直被用作治疗各种疾病的民间药物。用萝芙木树皮甲醇提取物（HABE）处理可抑制Ca9-22牙龈和HSC-3舌鳞状细胞癌细胞活力及BrdU掺入，并诱导凋亡性细胞死亡。流式细胞术分析表明，HABE处理通过增加Ca9-22细胞中的亚G1峰和使HSC-3细胞在G1期发生细胞周期阻滞，优先诱导凋亡性细胞死亡。在泛半胱天冬酶抑制剂zVAD-fmk存在的情况下进行HABE处理，可挽救两种OSCC细胞系的细胞活力。Bax与Bcl-2的比值随Bcl-2蛋白表达的降低而增加，并且在经HABE处理的Ca9-22和HSC-3细胞中检测到半胱天冬酶3的激活及随后PARP的裂解。此外，非细胞毒性浓度的HABE处理可抑制RANKL刺激的骨髓巨噬细胞中的破骨细胞形成。综上所述，HABE具有抑制OSCC细胞生长的活性和抗破骨细胞生成活性。因此，HABE可能是预防和治疗OSCC的一种有前景的替代和补充药物。
