Propolis extracts from the northern region of Thailand suppress cancer cell growth through induction of apoptosis pathways

Invest New Drugs. 2016 Dec;34(6):707-722. doi: 10.1007/s10637-016-0392-1. Epub 2016 Sep 21.


The continual increase in mortality rates and number of cancer cases is a matter of serious concern in developing countries. The incorporation of natural products into classical cancer treatment approaches is a promising direction. The mechanisms of A549 and HeLa cancer cell death induction by ethanolic extracts of propolis samples from Phayao, Chiang Mai, and Nan provinces in northern Thailand were investigated in this study. The propolis extract from Chiang Mai showed the highest antioxidant activity and the greatest total phenolic content. The propolis extract from Nan also exhibited the highest total flavonoid content. The proliferation of A549 and HeLa cells grown in the presence of the propolis extracts was suppressed in a dose- and time-dependent manner. Moreover, treatment of both cancer cells with the propolis extracts showed DNA fragmentation and significantly increased the number of the apoptotic cells. On A549 cells, the extrinsic and intrinsic pathways of caspase enzymes were activated by the propolis extracts from Phayao and Chiang Mai. In the case of the propolis extract from Nan, the mechanisms involved apoptosis on the A549 cells were caspase-independent pathway. The extrinsic pathway of the caspase enzyme was triggered by all of the propolis extracts on HeLa cells. Finally, oral administration of the propolis granule produced from the propolis extract from Nan resulted in extended survival of tumour-bearing mice. Therefore, propolis extracts from the northern region of Thailand demonstrated pharmacological properties, both antioxidant and anticancer activities. From these findings, it is evident that propolis extracts can be considered as a naturally obtained agent extremely useful in cancer treatment.

Keywords: Anticancer activity; Antiproliferative activity; Apoptosis; Caspase enzyme; Propolis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Proliferation / drug effects*
  • Flavonoids / pharmacology*
  • HeLa Cells
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Plant Extracts / pharmacology*
  • Propolis / chemistry*
  • Signal Transduction / drug effects
  • Thailand


  • Antioxidants
  • Flavonoids
  • Plant Extracts
  • Propolis
  • Caspases