Capsaicin

Capsaicin is a highly selective agonist for the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), a ligand-gated, nonselective cation channel, preferentially expressed on small-diameter sensory neurons ^[1]. capsaicin inhibits CYP1A2, CYP2C9, and CYP2C19, with IC50 values of 2.1, 2.0, and 3.2 μM, respectively, and inhibits CYP2B6, CYP2D6, CYP3A4, and CYP3A5 with extrapolated IC50 values of 24, 18, 38, and 12 μM, respectively ^[2].

Capsaicin inhibited Human cervical carcinoma HeLa growth (IC50 ～30 μM) and increased intracellular calcium, with effect blocked by capsazepine ^[3]. Capsaicin induced Human glioblastoma A172 apoptosis at ≥200 μM, not inhibited by capsazepine or BAPTA/AM 250 μM reduced basal generation of ROS and lipid peroxidation H2O2 reduced apoptosis, while NAC enhanced ^[4]. Capsaicin reduced Human urothelial cancer RT4 growth (IC50=80 μM) via a TRPV1-dependent process, induced cell cycle arrest in G0/G1 phase Apoptosis occurred ^[5].

Capsaicin pretreated ICR mice CD-1 mice with 2.5 μmol reduced VC-induced (5.8 mol) and TPA-promoted tumor incidence (by 62%) at 22 weeks (ICR) 1 μmol topical capsaicin 24 and 1 hr before, also significantly inhibited tumors induced by topical BP (0.3 μmol) then promoted with TPA (CD-1) ^[6]. Gavage with capsaicin significantly elevated phase II enzymes in liver and colon Oral capsaicin at 500 ppm for 4 weeks significantly inhibited ACF formation induced by AOM (20 mg/kg body weight, once a week for 2 weeks) In a 38-week study, 500 ppm capsaicin during the 4-week initiation phase significantly reduced (60%) incidence of colonic adenocarcinoma ^[7].

References:
[1]. Bley, K.; Boorman, G.; Mohammad, B.; McKenzie, D.; Babbar, S. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin. Toxicol. Pathol. 2012, 40, 847-873.
[2]. Babbar S., Chanda S., Bley K. (2010). Inhibition and induction of human cytochrome P450 enzymes in vitro by capsaicin. Xenobiotica 40, 807-16.
[3]. Takahata K., Chen X., Monobe K., Tada M. (1999). Growth inhibition of capsaicin on HeLa cells is not mediated by intracellular calcium mobilization. Life Sci 64, PL165-71.
[4]. Lee Y. S., Nam D. H., Kim J. A. (2000). Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett 161, 121-30.
[5]. Amantini C., Ballarini P., Caprodossi S., Nabissi M., Morelli M. B., Lucciarini R., Cardarelli M. A., Mammana G., Santoni G. (2009). Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis 30, 1320-29.
[6]. Surh Y. J., Lee R. C., Park K. K., Mayne S. T., Liem A., Miller J. A. (1995). Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis or tumorigenesis by vinyl carbamate and N-nitrosodimethylamine. Carcinogenesis 16, 2467-71.
[7]. Yoshitani S. I., Tanaka T., Kohno H., Takashima S. (2001). Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone. Int J Oncol 19, 929-39.

辣椒素是一种高度选择性的瞬时受体电位阳离子通道激动剂,亚家族 V,成员 1 (TRPV1),一种配体门控的非选择性阳离子通道,优先在小直径感觉神经元上表达 ^{[1]。辣椒素抑制 CYP1A2、CYP2C9 和 CYP2C19,IC50 值分别为 2.1、2.0 和 3.2 μM,抑制 CYP2B6、CYP2D6、CYP3A4 和 CYP3A5,外推 IC50 值分别为 24、18、38 和 12 μM sup>[2]}.

辣椒素抑制人宫颈癌 HeLa 的生长 (IC50 ~30 μM) 并增加细胞内钙,其作用被辣椒素 ^[3] 阻断。辣椒素在 ≥ 200 μM 时诱导人胶质母细胞瘤 A172 细胞凋亡,不受辣椒素或 BAPTA/AM 250 μM 的抑制,减少 ROS 和脂质过氧化的基础生成 H2O2 减少细胞凋亡,而 NAC 增强 ^[4]。辣椒素通过 TRPV1 依赖过程降低人尿路上皮癌 RT4 的生长 (IC50=80 μM),诱导细胞周期停滞在 G0/G1 期发生细胞凋亡^[5]。

用 2.5 μmol 辣椒素预处理 ICR 小鼠 CD-1 小鼠 22 周 (ICR) 时 VC 诱导的 (5.8 mol) 和 TPA 促进的肿瘤发生率降低 (62%) 1 μmol 外用辣椒素 24 小时和 1 小时前,也显着抑制局部 BP (0.3 μmol) 诱导的肿瘤,然后用 TPA (CD-1) ^[6] 促进。用辣椒素灌胃可显着提高肝脏和结肠中的 II 期酶口服 500 ppm 辣椒素 4 周可显着抑制 AOM 诱导的 ACF 形成（20 mg/kg 体重,每周一次,持续 2 周）在一项为期 38 周的研究中,500 ppm 辣椒素在 4 周起始阶段显着降低 (60%) 结肠腺癌的发病率^[7]。