Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata.
Andrographis paniculata plant extract is known to possess a variety of pharmacological activities. Andrographolide, the major constituent of the extract is implicated towards its pharmacological activity. We studied the cellular processes and targets modulated by andrographolide treatment in human cancer and immune cells. Andrographolide treatment inhibited the in vitro proliferation of different tumor cell lines, representing various types of cancers. The compound exerts direct anticancer activity on cancer cells by cell-cycle arrest at G0/G1 phase through induction of cell-cycle inhibitory protein p27 and decreased expression of cyclin-dependent kinase 4 (CDK4). Immunostimulatory activity of andrographolide is evidenced by increased proliferation of lymphocytes and production of interleukin-2. Andrographolide also enhanced the tumor necrosis factor-alpha production and CD marker expression, resulting in increased cytotoxic activity of lymphocytes against cancer cells, which may contribute for its indirect anticancer activity. The in vivo anticancer activity of the compound is further substantiated against B16F0 melanoma syngenic and HT-29 xenograft models. These results suggest that andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential for being developed as a cancer therapeutic agent.
Rajagopal
Sriram
S
Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad, India-500050. sriramrajagopal@drreddys.com
Kumar
R Ajaya
RA
Deevi
Dhanvanthri S
DS
Satyanarayana
Chitkala
C
Rajagopalan
R
R
D035685:Andrographis; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D007376:Interleukin-2; D010936:Plant Extracts; C030419:andrographolide