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Physalin F from Physalis minima L. triggers apoptosis-based cytotoxic mechanism in T-47D cells through the activation caspase-3- and c-myc-dependent pathways.

AbstractETHNOPHARMACOLOGICAL RELEVANCE:
Physalin F (a secosteroid derivative), is well recognized as a potent anticancer compound from Physalis minima L., a plant that is traditionally used to treat cancer. However, the exact molecular anticancer mechanism remains to be elucidated.
AIM OF THE STUDY:
We have recently reported the apoptosis-based cytotoxic effect of the chloroform extract of this plant. Here, we investigated the cytotoxicity and possible cell death mechanism elicited by the active constituent, physalin F on human breast T-47D carcinoma.
MATERIALS AND METHODS:
Cytotoxic-guided fractionation of the chloroform extract of Physalis minima has led to the isolation of physalin F. The cytotoxicity activity was assayed using MTS assay. The effect of the compound to induce apoptosis was determined by biochemical and morphological observations through DeadEnd Colorimetric and annexin V assays, respectively, and RT-PCR analysis of mRNA expression of the apoptotic-associated genes.
RESULTS:
Cytotoxicity screening of physalin F displayed a remarkable dose-dependent inhibitory effect on T-47D cells with lower EC50 value (3.60 μg/ml) than the crude extract. mRNA expression analysis revealed the co-regulation of c-myc- and caspase-3-apoptotic genes in the treated cells with the peak expression at 9 and 12h of treatment, respectively. This apoptotic mechanism is reconfirmed by DNA fragmentation and phosphatidylserine externalization.
CONCLUSION:
These findings indicate that physalin F may potentially act as a chemopreventive and/or chemotherapeutic agent by triggering apoptosis mechanism via the activation of caspase-3 and c-myc pathways in T-47D cells.
AuthorsKheng Leong Ooi, Tengku Sifzizul Tengku Muhammad, Shaida Fariza Sulaiman
JournalJournal of ethnopharmacology (J Ethnopharmacol) Vol. 150 Issue 1 Pg. 382-8 (Oct 28 2013) ISSN: 1872-7573 [Electronic] Ireland
PMID24051023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Secosteroids
  • physalin F
  • Caspase 3
Topics
  • Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
  • Apoptosis (drug effects)
  • Caspase 3 (genetics)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Humans
  • Physalis
  • Plant Extracts (chemistry)
  • Proto-Oncogene Proteins c-myc (genetics)
  • RNA, Messenger (metabolism)
  • Secosteroids (isolation & purification, pharmacology)

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