Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells

You Jin Kang, Hwa Jin Chung, Joo Won Nam, Hyen Joo Park, Eun Kyoung Seo, Yeong Shik Kim, Dongho Lee, Sang Kook Lee

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The potential antitumor activity of timosaponin A-III (1), a steroidal saponin from the rhizomes of Anemarrhena asphodeloides, was investigated in human colorectal cancer HCT-15 cells both in cell culture and in an in vivo murine xenograft model. Compound 1 inhibited the proliferation of cancer cells with cell-cycle arrest and induction of apoptosis. Cell-cycle arrest in the G0/G1 and G2/M phase by 1 was correlated with the down-regulation of cyclin A, cyclin B1, cyclin-dependent kinase 2 (CDK2), CDK4, proliferating cell nuclear antigen, and c-Myc. The increase of the sub-G1 peak by 1 was also closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspases, induction of cleaved poly-(ADP ribose) polymerase, and suppression of Bcl-xL and Bcl-2 expression. In an in vivo xenograft model, treatment with 1 (2 or 5 mg/kg body weight, three times/week, ip administration) for four weeks significantly suppressed tumor growth in athymic nude mice bearing HCT-15 cells, without any overt toxicity. Cell-cycle arrest and induction of apoptosis might be plausible mechanisms of actions for the observed antineoplastic activity of 1.

Original languageEnglish
Pages (from-to)701-706
Number of pages6
JournalJournal of Natural Products
Volume74
Issue number4
DOIs
Publication statusPublished - 2011 Apr 25

Fingerprint

Cell Cycle Checkpoints
Antineoplastic Agents
Colonic Neoplasms
Cells
Apoptosis
Heterografts
Nude Mice
Anemarrhena
Cyclin-Dependent Kinase 2
Cyclin B1
Cyclin A
Rhizome
Bearings (structural)
Poly(ADP-ribose) Polymerases
G2 Phase
Saponins
Proliferating Cell Nuclear Antigen
DNA Fragmentation
Caspases
Cell Division

ASJC Scopus subject areas

  • Complementary and alternative medicine
  • Molecular Medicine
  • Organic Chemistry
  • Analytical Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

Cite this

Kang, Y. J., Chung, H. J., Nam, J. W., Park, H. J., Seo, E. K., Kim, Y. S., ... Lee, S. K. (2011). Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells. Journal of Natural Products, 74(4), 701-706. https://doi.org/10.1021/np1007735

Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells. / Kang, You Jin; Chung, Hwa Jin; Nam, Joo Won; Park, Hyen Joo; Seo, Eun Kyoung; Kim, Yeong Shik; Lee, Dongho; Lee, Sang Kook.

In: Journal of Natural Products, Vol. 74, No. 4, 25.04.2011, p. 701-706.

Research output: Contribution to journalArticle

Kang, YJ, Chung, HJ, Nam, JW, Park, HJ, Seo, EK, Kim, YS, Lee, D & Lee, SK 2011, 'Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells', Journal of Natural Products, vol. 74, no. 4, pp. 701-706. https://doi.org/10.1021/np1007735
Kang, You Jin ; Chung, Hwa Jin ; Nam, Joo Won ; Park, Hyen Joo ; Seo, Eun Kyoung ; Kim, Yeong Shik ; Lee, Dongho ; Lee, Sang Kook. / Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells. In: Journal of Natural Products. 2011 ; Vol. 74, No. 4. pp. 701-706.
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