Gracillin (Synonyms: NSC 698787)

Gracillin, as a natural steroidal saponin component of D. quinqueloba, has antitumour, antimicrobial, antioxidant, pro‐apoptotic and anti‐inflammatory properties^[1].

In vitro efficacy test it shown that gracillin markedly inhibits the viability of RKO, SW480 and HCT116 cells, with IC₅₀ of 3.118, 2.671 and 5.473 μmol/L, respectively. Gracillin also stimulates apoptosis in human CRC cells in a dose-dependent manner (0, 2.5, 5.0 or 10.0 μmol/L)^[1]. In vitro experiment it exhibited that gracillin obviously inhibited the proliferation of A549 cells with IC₅₀ of 2.54 μmol/L in a concentration-dependent and time-dependent manner and induced morphological changes^[2]. Furthermore, gracillin inhibited the gastric tumor BGC823 cell proliferation in a concentration-dependent manner with IC₅₀ of 8.3 μM and gastric tumor SGC7901 cell proliferation with IC₅₀ of 8.9 μM in the range of 0-15 μM. At concentrations of 3 μM, 6 μM, and 12 μM, gracillin has TIPE2 induction in concentration-dependent manner^[3]. In vitro, gracillin has dose-dependent inhibitory effects on the mitochondrial function in various human cancer cell lines derived from lung, colorectum, prostate, pharynx, and liver with IC₅₀ of ~1-5 μM^[4].

In vivo, mice were administrated with 20 mg/kg gracillin significantly inhibited the growth of xenograft tumors^[5]. In vivo efficacy test it demenstrated that fish treated with 1 mg/kg gracillin carried significantly fewer parasites than the control, and acute toxicity LD50 of gracillin for grass carp was 1.64 mg/kg^[6].

References:
[1] Yang L, et al. Gracillin shows potent efficacy against colorectal cancer through inhibiting the STAT3 pathway. J Cell Mol Med. 2021 Jan;25(2):801-812.
[2] Yang J, et al. Gracillin Isolated from Reineckia carnea Induces Apoptosis of A549 Cells via the Mitochondrial Pathway. Drug Des Devel Ther. 2021 Jan 20;15:233-243.
[3] Liu W, et al. Beneficial Effects of Gracillin From Rhizoma Paridis Against Gastric Carcinoma via the Potential TIPE2-Mediated Induction of Endogenous Apoptosis and Inhibition of Migration in BGC823 Cells. Front Pharmacol. 2021 Sep 24;12:669199.
[4] Min HY, et al. The natural compound gracillin exerts potent antitumor activity by targeting mitochondrial complex II. Cell Death Dis. 2019 Oct 24;10(11):810.
[5] Min HY, et al. Potent Anticancer Effect of the Natural Steroidal Saponin Gracillin Is Produced by Inhibiting Glycolysis and Oxidative Phosphorylation-Mediated Bioenergetics. Cancers (Basel). 2020 Apr 8;12(4):913.
[6] Zheng W, et al. Antiparasitic efficacy of Gracillin and Zingibernsis newsaponin from Costus speciosus (Koen ex. Retz) Sm. against Ichthyophthirius multifiliis. Parasitology. 2015 Mar;142(3):473-9.