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 timedependent manner. The median inhibitory concentration (IC 50 ) at 24, 48, and 72 h were 28.31, 15.58, and 6.14 mg/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) (p50.01). Diterpenoid C also induced apoptosis and arrested cell cycle. It showed the highest apoptosis rate (98.20 ± 0.91%) at 70 mg/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.

Herbal Compound “Jiedu Huayu” Reduces Liver Injury in Rats via Regulation of IL‐2, TLR4, and PCNA Expression Levels

“…Oldenlandia diffusa inhibits inflammation via suppression of caspase-1 activation in mouse peritoneal macrophages [ 22 ]. Radix curcumae was found to reduce proinflammatory cytokines by blocking NF- κ B signal pathways [ 23 ]; however, it was also found to regulate cell proliferation and apoptosis [ 24 ]. Acorus gramineus was found to have a therapeutical role in disorders of the central nervous system such as convulsions and epilepsy [ 25 ].…”

A Review of the Ethnomedicinal Uses, Biological Activities, and Triterpenoids of Euphorbia Species

“…This has been the reason behind the failure of many cancer therapies. However, the glycoprotein (P-gp or Pgp), which is normally programmed with multidrug gene 1 (MDR1) pumps out of the cell any foreign materials/substances [ 87 ]. Therefore, targeting compounds that can inhibit these proteins can help in addressing drug resistance and also reduce the migration of cancer cells.…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…It has been reported that matrine induces growth inhibition and apoptosis of M21 and A375 (human melanoma cell lines) by activating the PTEN pathway (17). Matrine also induces apoptosis of A549 and 95D (human lung cancer cell lines) via the PI3K/Akt/mTOR signaling diterpenoid C functions as an inhibitor of proliferation and inducer of apoptosis through the MAPK signaling pathway (29).…”