Pharmacological Research 51 (2005) 437–443 Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandiflorum in human lung carcinoma cells Dong Il Park a , Jae Hun Lee a , Sung-Kwon Moon b , Cheorl-Ho Kim c , Yong Tae Lee a , JaeHun Cheong d , Byung Tae Choi a , Yung Hyun Choi a,∗ a Department of Oriental Medicine, Dongeui University College of Oriental Medicine and Research Institute of Oriental Medicine, Busan 614-052, Republic of Korea b Department of Food and Biotechnology, Chungju National University, Chungju 380-702, Republic of Korea c Department of Oriental Medicine, Dongguk University College of Oriental Medicine, Kyungju 780-714, Republic of Korea d Department of Molecular Biology, Pusan National University, Busan 609-735, Republic of Korea Accepted 4 November 2004 Abstract The objective of the present study was to investigate the effect of aqueous extract from the root of Platycodon grandiflorum (AEPG) on the cell growth and apoptosis in human lung carcinoma cell line A549. Exposure of A549 cells to AEPG resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometry analysis. This increase in apoptosis was associated with a decrease in Bcl-2 expression, an increase of Bax and an activation of caspase-3. AEPG treatment markedly inhibited the activity of telomerase in a dose-dependent fashion. Additionally, the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by AEPG treatment. These findings suggest that the apoptotic events by AEPG were associated with the diminished telomerase activity and down-regulation of Bcl-2 expression. © 2004 Elsevier Ltd. All rights reserved. Keywords: Platycodon grandiflorum; Apoptosis; Bcl-2; Telomerase; hTERT 1. Introduction It is now well accepted that apoptosis is a physiological phenomenon that plays an important role in the regulation of tissue development and homeostasis. Deregulation of apop- tosis has been shown to contribute to the pathogenesis of a number of human diseases including cancer [1,2]. There are apparently many factors, including Bcl-2 family and caspase proteases, involved in the apoptotic process through the ex- pression of genes, and the characterization of the function of these gene products will help to define the process of cell death at the molecular levels [3–5]. In addition to deregulation of apoptosis, it is increasingly clear that the process of neoplasia is characterized by the ∗ Corresponding author. Tel.: +82 51 850 7413; fax: +82 51 853 3578. E-mail address: choiyh@deu.ac.kr (Y.H. Choi). activation of telomerase that adds telomeric repeats to the ends of replicating chromosomes, telomeres [6,7]. Telom- eres are essential units that stabilize the ends of eukary- otic chromosome and prevent the loss of genetic informa- tion. In normal human somatic cells, which show little or no telomerase activity to synthesize new telomeres, the telomer- icDNAs progressively shorten with each cell division [6,8]. Critically short telomeres are suggested to cause irreversible cell growth arrest and cellular senescence [6,7,9,10]. Con- versely, most tumor cells have mechanisms that compensate for telomere shortening, most commonly through the acti- vation of telomerase, allowing them to stably maintain their telomeres and grow indefinitely. These observations suggest that telomerase reactivation is a rate-limiting step in cellular immortality and carcinogenesis, and telomerase repression can act as a tumor-suppressive mechanism. Telomere length in human is primarily controlled by three major components; 1043-6618/$ – see front matter © 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2004.11.003