Diterpenoid C of Radix Curcumae: an inhibitor of proliferation and inducer of apoptosis in human colon adenocarcinoma cells acting via inhibiting MAPK signaling pathway

Abstract

Context: Radix Curcumae is a traditional Chinese medicine that possesses antitumor properties, from which a new compound, diterpenoid C, was previously isolated and characterized.

Objective: In this study, using human colon adenocarcinoma SW620 cells, we further investigated the antitumor effects of diterpenoid C and the underlying mechanisms.

Materials and methods: Cell proliferation was assessed with the MTT assay. Cell apoptosis and cell-cycle progression were analyzed with flow cytometry. The expression of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK), and their phosphorylated forms, as well as caspase-3 protein levels were examined with Western blots.

Results: Diterpenoid C could inhibit the proliferation of SW620 cells in a dose- and time-dependent manner. The median inhibitory concentration (IC50) at 24, 48, and 72 h were 28.31, 15.58, and 6.14 μg/ml, respectively. The inhibition of proliferation was found to be statistically significant as compared with the well-established drugs 5-fluorouracil (5-Fu) and oxaliplatin (L-OHP) (p < 0.01). Diterpenoid C also induced apoptosis and arrested cell cycle. It showed the highest apoptosis rate (98.20 ± 0.91%) at 70 μg/ml, at 72 h. Meanwhile, diterpenoid C suppressed the phosphorylation of ERK, JNK, and p38 MAPK proteins, and markedly induced the cleavage of caspase 3.

Discussion and conclusion: Diterpenoid C inhibits proliferation and induces apoptosis of cancer cells by suppressing the MAPK signaling pathway and inducing apoptotic factor caspase-3. Our results suggest that this novel compound might become a potent chemotherapeutic agent for the treatment of colon cancer and further studies are warranted.

Keywords: Apoptosis; MAPK; SW620 cell; Zingiberaceae; caspase-3; colon cancer; diterpenoid C.