Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Busandaehak-ro 49, Yangsan, Gyeongnam 50612, Republic of Korea; Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Yangsan, Gyeongnam 50612, Republic of Korea; Graduate Training Program of Korean Medicine for Healthy-aging, Pusan National University, Busandaehak-ro 49, Yangsan, Gyeongnam 50612, Republic of Korea.
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Busandaehak-ro 49, Yangsan, Gyeongnam 50612, Republic of Korea; Healthy Aging Korean Medical Research Center, Pusan National University, Busandaehak-ro 49, Yangsan, Gyeongnam 50612, Republic of Korea.
J Pharmacol Sci. 2018 Oct;138(2):146-154. doi: 10.1016/j.jphs.2018.10.005. Epub 2018 Oct 18.
Cinnamomum cassia Blume has been widely reported as the anti-tumor agent. However, the precise mechanism underlying its pro-apoptotic action is still not clear. Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer inhibition. In this study, we performed to investigate the anti-tumor action of C. cassia is mediated by PDHK inhibition. The inhibition of water-extracted branch of C. cassia (WBCC) on the activity of PDHK using both in vitro and cell-based kinase assay were examined in several lung cancer cells. WBCC reduced viabilities of several lung cancer cells with minimal cytotoxicity on normal bronchial epithelial cells. WBCC decreased lactate production through inhibiting activity of PDHK. In consequence of PDHK inhibition, WBCC increased ROS production, which damage mitochondria membrane stability. In addition, WBCC induced ROS- and mitochondria-dependent apoptotic cell death. Among the components of WBCC, cinnamic acid was founded as a major inhibitor on PDHK activity. This is first report that WBCC induces apoptosis of lung cancer cells through inhibiting PDHK activity. Our findings suggest that WBCC and cinnamic acid can be potential candidates for developing novel anti-cancer drugs through glycolysis metabolism.
肉桂已被广泛报道为抗肿瘤药物。然而，其促凋亡作用的确切机制尚不清楚。通过抑制丙酮酸脱氢酶激酶（PDHK）来抑制有氧糖酵解是抑制癌症的一种很有前途的策略。在这项研究中，我们研究了肉桂通过抑制 PDHK 发挥抗肿瘤作用。我们使用体外和基于细胞的激酶测定法，研究了肉桂的水提枝（WBCC）对几种肺癌细胞中 PDHK 活性的抑制作用。WBCC 降低了几种肺癌细胞的活力，对正常支气管上皮细胞的细胞毒性最小。WBCC 通过抑制 PDHK 的活性减少乳酸的产生。由于 PDHK 的抑制，WBCC 增加了 ROS 的产生，破坏了线粒体膜的稳定性。此外，WBCC 诱导 ROS 和线粒体依赖性细胞凋亡。在 WBCC 的成分中，发现肉桂酸是 PDHK 活性的主要抑制剂。这是首次报道 WBCC 通过抑制 PDHK 活性诱导肺癌细胞凋亡。我们的研究结果表明，WBCC 和肉桂酸可以成为通过糖酵解代谢开发新型抗癌药物的潜在候选药物。
