title: 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: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University , Hangzhou, Zhejiang Province , China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhong-Jun
authors.initials: ZJ
authors.lastname: Ma
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D030024:Curcuma / Q000737:chemistry*; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D009944:Organoplatinum Compounds; C585952:diterpenoid C, Radix curcumae; D000077150:Oxaliplatin; D053148:Caspase 3; D005472:Fluorouracil
keywords: Apoptosis; MAPK; SW620 cell; Zingiberaceae; caspase-3; colon cancer; diterpenoid C