Andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity.
Andrographolide, a major constituent of Andrographis paniculata, was previously shown to exhibit anti-inflammatory, antiviral, and anticancer activities. The anticancer activity of andrographolide includes growth suppression, apoptosis promotion, antiangiogenesis, and antitransformation. However, the effect of andrographolide on cancer metastasis, the most malignant feature of cancer, has not been elucidated extensively. In the present study, we demonstrated that andrographolide at nontoxic to subtoxic concentrations (0.3-3 µM) suppressed the invasion ability of CT26 cells in Matrigel-based invasion assays. In addition, the expression of cell adhesion regulators (β-catenin and ILK) was not altered by andrographolide treatment. However, andrographolide indeed inhibited matrix metalloproteinase 2 (MMP2) activity without affecting its expression. Furthermore, the activation of ERK, but not Akt, was attenuated by andrographolide treatment. Notably, a similar inhibitory effect of andrographolide on the invasion and MMP2 activity of the human colon cancer cell line HT29 was also observed. In summary, our results indicate that andrographolide exhibits anti-invasive activity against colon cancer cells via inhibition of MMP2 activity.
Chao
Hsueh-Ping
HP
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
Kuo
Cheng-Deng
CD
Chiu
Jen-Hwey
JH
Fu
Shu-Ling
SL
D035685:Andrographis / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000099200:Scaffold Protein ILK
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C030419:andrographolide