Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Departments of Pharmacognosy and Pharmaceutical Botany, Chulalongkorn University, Bangkok, 10330, Thailand.
J Nat Med. 2018 Jun;72(3):615-625. doi: 10.1007/s11418-018-1186-x. Epub 2018 Feb 27.
Failure of current chemotherapeutic drugs leads to the recurrence of tumor pathology and mortality in lung cancer patients. This study aimed to evaluate the anticancer activity and related mechanisms of 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang, in human lung cancer cells. Cytotoxicity of TDB (0-300 µM) in different types of human lung cancer cells (H460, H292 and H23) and human dermal papilla cells (DPCs) was evaluated via MTT viability assay. Selective anticancer activity of TDB against human lung cancer cells was demonstrated with a high IC (approximately > 300 µM) in DPCs, while IC in human lung cancer H460, H292 and H23 cells was approximately 100 ± 5.18, 100 ± 8.73 and 188.89 ± 8.30 µM, respectively. After treatment with 50 µM of TDB for 24 h, flow cytometry analysis revealed the significant increase of early and late apoptosis with absence of necrosis cell death in human lung cancer cells. The up-regulation of p53, a tumor-suppressor protein, was elucidated in human lung cancer cells treated with 10-50 µM of TDB. Alteration to down-stream signaling of p53 including activation of pro-apoptosis protein (Bcl-2-associated X protein; Bax), reduction of anti-apoptosis (B cell lymphoma 2; Bcl-2 and myeloid cell leukemia 1; Mcl-1) and suppression on protein kinase B (Akt) survival pathway were notified in TDB-treated lung cancer cells. The information obtained from this study strengthens the potential development of TDB as an anticancer compound with a favorable human safety profile and high efficacy.
目前的化疗药物的失败导致肿瘤病理学的复发和肺癌患者的死亡率。本研究旨在评估 4,5,4'-三羟基-3,3'-二甲氧基二苄基（TDB），一种从石斛中提取的二苄基，对人肺癌细胞的抗癌活性和相关机制。通过 MTT 活力测定法评估 TDB（0-300µM）在不同类型的人肺癌细胞（H460、H292 和 H23）和人真皮乳头细胞（DPCs）中的细胞毒性。TDB 对人肺癌细胞的选择性抗癌活性表现为在 DPCs 中的高 IC（约>300µM），而在人肺癌 H460、H292 和 H23 细胞中的 IC 分别约为 100±5.18、100±8.73 和 188.89±8.30µM。用 50µM 的 TDB 处理 24 小时后，流式细胞术分析显示早期和晚期凋亡显著增加，而坏死细胞死亡不存在于人肺癌细胞中。在人肺癌细胞中用 10-50µM 的 TDB 处理后，上调了肿瘤抑制蛋白 p53。p53 的下游信号改变，包括促凋亡蛋白（Bcl-2 相关 X 蛋白；Bax）的激活、抗凋亡蛋白（B 细胞淋巴瘤 2；Bcl-2 和髓样细胞白血病 1；Mcl-1）的减少和蛋白激酶 B（Akt）生存途径的抑制，在 TDB 处理的肺癌细胞中得到了通知。本研究获得的信息加强了 TDB 作为一种具有良好人类安全性和高效性的抗癌化合物的潜在开发。
