Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon cancer

April B. Cabang, Keya De Mukhopadhyay, Sarah Meyers, James L Morris, Paul V. Zimba, Michael J Wargovich

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers and the 3rd leading cause of cancer-related mortality. The emergence of drug resistance poses a major challenge in CRC care or treatment. This can be addressed by determining cancer mechanisms, discovery of druggable targets, and development of new drugs. In search for novel agents, aquatic microorganisms offer a vastly untapped pharmacological source that can be developed for cancer therapeutics. In this study, we characterized the anti-colorectal cancer potential of euglenophycin, a microalgal toxin from Euglena sanguinea. The toxin (49.1-114.6 μM) demonstrated cytotoxic, anti-proliferative, anti-clonogenic, and anti-migration effects against HCT116, HT29, and SW620 CRC cells. We identified G1 cell cycle arrest and cell type - dependent modulation of autophagy as mechanisms of growth inhibition. We validated euglenophycin's anti-tumorigenic activity in vivo using CRL:Nu(NCr)Foxn1nu athymic nude mouse CRC xenograft models. Intraperitoneal toxin administration (100 mg/kg; 5 days) decreased HCT116 and HT29 xenograft tumor volumes (n=10 each). Tumor inhibition was associated with reduced expression of autophagy negative regulator mechanistic target of rapamycin (mTOR) and decreased trend of serum pro-inflammatory cytokines. Together, these results provide compelling evidence that euglenophycin can be a promising anti-colorectal cancer agent targeting multiple cancer-promoting processes. Furthermore, this study supports expanding natural products drug discovery to freshwater niches as prospective sources of anti-cancer compounds.

Original languageEnglish (US)
Pages (from-to)104347-104358
Number of pages12
JournalOncotarget
Volume8
Issue number61
DOIs
StatePublished - Jan 1 2017

Fingerprint

Therapeutic Uses
Colonic Neoplasms
Colorectal Neoplasms
Neoplasms
Autophagy
Heterografts
Nude Mice
Euglena
G1 Phase Cell Cycle Checkpoints
Sirolimus
Drug Discovery
euglenophycin
Tumor Burden
Biological Products
Fresh Water
Drug Resistance
Pharmacology
Cytokines
Mortality
Growth

Keywords

  • Autophagy
  • Colon cancer
  • Euglenophycin
  • Ichthyotoxin
  • Therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Cabang, A. B., De Mukhopadhyay, K., Meyers, S., Morris, J. L., Zimba, P. V., & Wargovich, M. J. (2017). Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon cancer. Oncotarget, 8(61), 104347-104358. https://doi.org/10.18632/oncotarget.22238

Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon cancer. / Cabang, April B.; De Mukhopadhyay, Keya; Meyers, Sarah; Morris, James L; Zimba, Paul V.; Wargovich, Michael J.

In: Oncotarget, Vol. 8, No. 61, 01.01.2017, p. 104347-104358.

Research output: Contribution to journalArticle

Cabang, AB, De Mukhopadhyay, K, Meyers, S, Morris, JL, Zimba, PV & Wargovich, MJ 2017, 'Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon cancer', Oncotarget, vol. 8, no. 61, pp. 104347-104358. https://doi.org/10.18632/oncotarget.22238
Cabang, April B. ; De Mukhopadhyay, Keya ; Meyers, Sarah ; Morris, James L ; Zimba, Paul V. ; Wargovich, Michael J. / Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon cancer. In: Oncotarget. 2017 ; Vol. 8, No. 61. pp. 104347-104358.
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