Periplocin is one of the cardenolides isolated from Periploca sepium, with anti-proliferative activities[1]. Periplocin can increase the caspase-3, -8, and -9 enzyme activities and decrease PI3K/Akt/mTOR activity to trigger apoptosis[2]. Periplocin has been widely used as an anticancer agent in cellular and animal models to inhibit cancer progression[3].
In vitro, Periplocin treatment significantly inhibited the proliferation of Muc-Myx2a, Muc-Myx2b and T60 cells with IC50 values of 0.25µM, 0.30µM, and 0.10µM, respectively[4]. Periplocin treatment at 50µM for 24 hours significantly activated RIP3/MLKL signaling pathway and induced necroptosis in TPC-1 cells[5]. Treatment of SK-HEP-1 cells with 500nM Periplocin for 48 hours significantly induced cell cycle arrest and apoptosis, accompanied by the inhibition of AKT/NF-κB signaling pathway[6].
In vivo, Periplocin treatment via intraperitoneal injection at a dose of 15mg/kg/day for 14 days notably reduced tumor growth in A549 cell-xenograft mice and decreased Ki67 expression in the tumor tissues[7]. Daily intraperitoneal injection of Periplocin at a dose of 5mg/kg for 8 weeks reduced bone loss in ovariectomy-induced osteoporotic mice[8].
References:
[1] Lohberger B, Wagner S, Wohlmuther J, et al. Periplocin, the most anti-proliferative constituent of Periploca sepium, specifically kills liposarcoma cells by death receptor mediated apoptosis[J]. Phytomedicine, 2018, 51: 162-170.
[2] Liu X, Liu J, Yan B, et al. Study of the PI3K/Akt/mTOR signaling pathway in vitro and molecular docking analysis of periplocin inhibits cell cycle progression and induces apoptosis in MDA‐MB‐231[J]. Environmental Toxicology, 2024, 39(1): 444-456.
[3] Bae E S, Byun W S, Ock C W, et al. Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells[J]. Biomedicine & Pharmacotherapy, 2023, 157: 114039.
[4] Lohberger B, Bernhart E, Stuendl N, et al. Periplocin mediates TRAIL-induced apoptosis and cell cycle arrest in human myxofibrosarcoma cells via the ERK/p38/JNK pathway[J]. Phytomedicine, 2020, 76: 153262.
[5] Ding L, Wen F, Zeng L, et al. Periplocin induces necroptosis in papillary thyroid carcinoma through DR4 mediated RIPK3 and MLKL signaling[J]. Scientific Reports, 2025, 15(1): 20383.
[6] Lin J P, Huang M H, Sun Z T, et al. Periplocin inhibits hepatocellular carcinoma progression and reduces the recruitment of MDSCs through AKT/NF-κB pathway[J]. Life Sciences, 2023, 324: 121715.
[7] Wang J, Zhu Y, Song J, et al. Periplocin potentiates ferroptotic cell death in non-small cell lung cancer by inducing the degradation of Nrf2[J]. Cancer Cell International, 2025, 25(1): 294.
[8] Zhang X, Sun Z, Zhang Y, et al. Periplocin targets low density lipoprotein receptor-related protein 4 to attenuate osteoclastogenesis and protect against osteoporosis[J]. Biochemical Pharmacology, 2023, 211: 115516.
Periplocin是从Periploca sepium分离的强心苷类化合物，具有抗增殖活性[1]。Periplocin可通过增强caspase-3、-8、-9酶活性并抑制PI3K/Akt/mTOR通路进而诱导细胞凋亡[2]。Periplocin已作为抗癌剂广泛应用于细胞和动物模型中抑制癌症进展[3]。
在体外，Periplocin处理48小时能显著抑制Muc-Myx2a、Muc-Myx2b和T60细胞增殖，IC50值分别为0.25µM、0.30µM和0.10µM[4]。使用50µM的Periplocin处理TPC-1细胞24小时，可显著激活RIP3/MLKL信号通路并诱导坏死性凋亡[5]。用500nM的Periplocin处理SK-HEP-1细胞48小时，能显著诱导细胞周期阻滞和凋亡，同时抑制AKT/NF-κB信号通路[6]。
在体内，每日腹腔注射15mg/kg/day剂量的Periplocin连续14天，可显著抑制A549细胞移植瘤小鼠的肿瘤生长，并降低肿瘤组织中Ki67的表达[7]。每日腹腔注射5mg/kg剂量的Periplocin持续8周，能减轻卵巢切除诱导的骨质疏松小鼠的骨量丢失[8]。