Yoo Eun Seon, Choo Gang Sik, Kim Sung Hyun, Woo Joong Seok, Kim Hyeong Jin, Park Young Seok, Kim Byeong Soo, Kim Sang Ki, Park Byung Kwon, Cho Sung Dae, Nam Jeong Seok, Choi Chang Sun, Che Jeong Hwan, Jung Ji-Youn
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, Republic of Korea.
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
Anticancer Res. 2019 Apr;39(4):1883-1892. doi: 10.21873/anticanres.13296.
BACKGROUND/AIM: Piperine is a major pungent alkaloid present in black pepper (Piper nigrum L). This study investigated the potential anticancer effects of piperine on human melanoma cells and explored the potential pharmacological mechanisms in vitro and in vivo.
Studies were performed using the MTT assay, 4',6-diamidino-2-phenylindole (DAPI) staining, western blotting, a xenograft model, the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and immunohistochemistry.
Piperine inhibited the growth of melanoma cells. Several apoptotic events were observed following treatment, as revealed by DAPI staining. Piperine increased the expression of BCL2-associated X, apoptosis regulator (BAX), cleaved poly(ADP-ribose)polymerase, cleaved caspase-9, phospho-c-Jun N-terminal kinase and phospho-p38, and reduced that of B-cell lymphoma 2 (BCL2), X-chromosome-linked inhibitor of apoptosis, and phospho-extracellular signal-regulated protein kinase (ERK1/2) in a concentration-dependent manner. Treatment of mice for 4 weeks with piperine inhibited tumor growth without apparent toxicity. Piperine increased the expression of apoptotic cells and cleaved-caspase-3 protein and reduced the expression of phospho-ERK1/2 protein in melanoma tumors.
Piperine suppressed the growth of human melanoma cells by the induction of apoptosis via the inhibition of tumor growth of human melanoma cells and tumor xenograft models.
背景/目的：胡椒碱是黑胡椒（Piper nigrum L）中主要的辛辣生物碱。本研究调查了胡椒碱对人黑色素瘤细胞的潜在抗癌作用，并在体外和体内探索了其潜在的药理机制。
采用MTT法、4',6-二脒基-2-苯基吲哚（DAPI）染色、蛋白质印迹法、异种移植模型、末端脱氧核苷酸转移酶dUTP缺口末端标记法和免疫组织化学进行研究。
胡椒碱抑制黑色素瘤细胞的生长。DAPI染色显示，处理后观察到一些凋亡事件。胡椒碱以浓度依赖的方式增加凋亡调节因子BCL2相关X蛋白（BAX）、裂解的聚（ADP-核糖）聚合酶、裂解的半胱天冬酶-9、磷酸化c-Jun氨基末端激酶和磷酸化p38的表达，并降低B细胞淋巴瘤2（BCL2）、X染色体连锁凋亡抑制蛋白和磷酸化细胞外信号调节蛋白激酶（ERK1/2）的表达。用胡椒碱处理小鼠4周可抑制肿瘤生长且无明显毒性。胡椒碱增加黑色素瘤肿瘤中凋亡细胞和裂解的半胱天冬酶-3蛋白的表达，并降低磷酸化ERK1/2蛋白的表达。
胡椒碱通过抑制人黑色素瘤细胞和肿瘤异种移植模型的肿瘤生长来诱导凋亡，从而抑制人黑色素瘤细胞的生长。
