Chelerythrine Chloride is a potent and cell-permeable inhibitor of protein kinase C (PKC), with an IC50 value of 660nM[1]. Chelerythrine Chloride acts by selectively binding to the catalytic domain of PKC, inhibiting its activity through competition with the substrate phosphoacceptor rather than ATP[2]. Chelerythrine Chloride is commonly used in studies related to anti-inflammatory effects, apoptosis mechanisms, tumor biology, and immunoregulation[3,4].
In vitro, treatment of NCI-H1703 cells with Chelerythrine Chloride (3μg/mL) for 24h significantly induces the activity of caspase-3 and caspase-7, promoting apoptosis. When NCI-H1703 cells were treated with Chelerythrine Chloride (1.5, 3, 6μg/mL) for 3 weeks, a dose-dependent inhibition of colony formation in soft agar was observed[5]. Treatment of human neutrophils (PMN) with Chelerythrine Chloride (10μM) for 4h induced apoptosis in 93% of cells, which was significantly higher than the UV-irradiation group (70%)[6].
In vivo, administration of Chelerythrine Chloride (2.5mg/kg; i.p.) to nude mice bearing SQ-20B tumor cells on days 8, 10, and 12 after tumor implantation significantly delayed tumor growth[7]. Daily treatment with Chelerythrine Chloride (10mg/kg/day; i.p.) for 4 weeks in mice bearing TSC2-deficient ELT3-Luciferase xenograft tumors significantly inhibited tumor volume growth (by 57%) without causing weight loss or apparent toxicity[8].
References:
[1] HERBERT J M, AUGEREAU J M, GLEYE J, et al. Chelerythrine is a potent and specific inhibitor of protein kinase C[J]. Biochemical and biophysical research communications, 1990, 172(3): 993-999.
[2] SIOMMOING X, GRESSIER B, DINE T, et al. Investigation of the inhibitory effects of chelerythrine chloride on the translocation of the protein kinase c βi, βii, ζ in human neutrophils[J]. Il Farmaco, 2001, 56(11): 859-865.
[3] ZHANG Z, GUO Y, ZHANG J, et al. Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 cell[J]. Archives of pharmacal research, 2011, 34(5): 791-800.
[4] NIU X F, ZHOU P, LI W F, et al. Effects of chelerythrine, a specific inhibitor of cyclooxygenase-2, on acute inflammation in mice[J]. Fitoterapia, 2011, 82(4): 620-625.
[5] HENG W S, CHEAH S C. Chelerythrine chloride downregulates β-catenin and inhibits stem cell properties of non-small cell lung carcinoma[J]. Molecules, 2020, 25(1): 224.
[6] SWEENEY J F, NGUYEN P K, ATKINS K B, et al. Chelerythrine chloride induces rapid polymorphonuclear leukocyte apoptosis through activation of caspase-3[J]. Shock, 2000, 13(6): 464-471.
[7] CHMURA S J, DOLAN M E, CHA A, et al. In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo[J]. Clinical Cancer Research, 2000, 6(2): 737-742.
[8] MEDVETZ D, SUN Y, LI C, et al. High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting[J]. Molecular Cancer Research, 2015, 13(1): 50-62.
Chelerythrine Chloride是一种强效且可渗透细胞的蛋白激酶C（protein kinase C, PKC）抑制剂，IC50值为660nM[1]。Cheleryt hrine Chloride通过选择性结合PKC的催化结构域发挥作用，以竞争底物磷酸受体而非ATP的方式抑制PKC活性[2]。Chelerythrine Chloride通常用于抗炎、细胞凋亡机制、肿瘤生物学及免疫调节相关的研究[3,4]。
在体外，Chelerythrine Chloride（3μg/mL）处理NCI-H1703细胞24h，能显著诱导caspase-3和caspase-7的活性，促进细胞凋亡。Chelerythrine Chloride（1.5, 3, 6μg/mL）处理NCI-H1703细胞3周，能剂量依赖性地抑制其在软琼脂中的菌落形成能力[5]。Chelerythrine Chloride（10μM）处理人中性粒细胞（PMN）4h，可诱导93%的细胞发生凋亡，显著高于紫外线照射组（70%）[6]。
在体内，Chelerythrine Chloride（2.5mg/kg; i.p.）治疗携带SQ-20B肿瘤细胞的裸鼠，分别在移植肿瘤细胞后第8、10、12天给药，显著延迟了肿瘤的生长[7]。Chelerythrine Chloride（10mg/kg/day; i.p.）治疗携带TSC2缺失的ELT3-Luciferase细胞异种移植瘤的小鼠4周，可显著抑制肿瘤体积的增长（减少57%），且无体重下降或明显毒性[8]。