Apoptosis of human gastric cancer SGC‑7901 cells induced by podophyllotoxin
- Authors:
View Affiliations
Affiliations: Engineering Research Center of Natural Anticancer Drugs, Ministry of Education, Harbin, Heilongjiang 150076, P.R. China
- Published online on: March 6, 2014 https://doi.org/10.3892/etm.2014.1606
-
Pages:
1317-1322
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Abstract
Numerous studies have demonstrated that podophyllotoxin and its derivatives exhibit antitumor effects. The aim of the present study was to investigate SGC‑7901 cell apoptosis and the underlying mechanism induced by podophyllotoxin. SGC‑7901 cells were treated with varying concentrations of podophyllotoxin. MTT assays and flow cytometry were used to evaluate the effects of podophyllotoxin on the proliferation and apoptosis of SGC‑7901 cells, while fluorescence inverted microscopy was used to observe the morphology of SGC‑7901 cells that had been dyed with Hoechst 33258. In addition, laser scanning confocal microscopy was used to analyze the mitochondrial membrane potential (MMP) of SGC‑7901 cells dyed with Rhodamine 123. Western blotting was performed to analyze the expression levels of cytochrome c (cyt‑c), caspase‑9 and caspase‑3 in the SGC‑7901 cells. The results indicated that podophyllotoxin was capable of inhibiting growth and inducing the apoptosis of SGC‑7901 cells in a dose‑dependent manner, causing cell cycle arrest at the G2/M phase. After 48 h of treatment, the apoptotic morphology of SGC‑7901 cells was clear, exhibiting cell protuberance, concentrated cytoplasms and apoptotic bodies. Following 24 h of treatment, the MMP of the SGC‑7901 cells decreased. In addition, after 48 h, the expression of cyt‑c was shown to be upregulated, while the expression levels of pro‑caspase‑9 and pro‑caspase‑3 in the SGC‑7901 cells were shown to be downregulated. In conclusion, apoptosis can be induced in SGC‑7901 cells by podophyllotoxin, potentially via a mitochondrial pathway, indicating that podophyllotoxin may be a potent agent for cancer treatment.
View References
|
1
|
Hu Y, Fang JY and Xiao SD: Can the
incidence of gastric cancer be reduced in the new century? J Dig
Dis. 14:11–15. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
2
|
Ji YB, Ji CF and Zhang H: Laminarin
induces apoptosis of human colon cancer LOVO cells through a
mitochondrial pathway. Molecules. 17:9947–9960. 2012. View Article : Google Scholar : PubMed/NCBI
|
|
3
|
Ji YB, Ji CF, Yue L and Xu H: Saponins
isolated from Asparagus induce apoptosis in human hepatoma cell
line HepG2 through a mitochondrial-mediated pathway. Curr Oncol.
19(Suppl 2): eS1–eS9. 2012.PubMed/NCBI
|
|
4
|
Wang B, Chen L, Zhen H, et al: Proteomic
changes induced by podophyllotoxin in human cervical carcinoma HeLa
cells. Am J Chin Med. 41:163–175. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
5
|
Yang TM, Qi SN, Zhao N, et al: Induction
of apoptosis through caspase-independent or caspase-9-dependent
pathway in mouse and human osteosarcoma cells by a new nitroxyl
spin-labeled derivative of podophyllotoxin. Apoptosis. 18:727–738.
2013. View Article : Google Scholar : PubMed/NCBI
|
|
6
|
Rojas-Sepúlveda AM, Mendieta-Serrana M,
Mojica MY, et al: Cytotoxic podophyllotoxin type-lignans from the
steam bark of Bursera fagaroides var. fagaroides. Molecules.
17:9506–9519. 2012.PubMed/NCBI
|
|
7
|
Xu H, Lv M and Tian X: A review on
hemisynthesis, biosynthesis, biological activities, mode of action,
and structure-activity relationship of podophyllotoxins: 2003–2007.
Curr Med Chem. 16:327–349. 2009.PubMed/NCBI
|
|
8
|
Hartmann JT and Lipp HP: Camptothecin and
podophyllotoxin derivatives: inhibitors of topoisomerase I and II -
mechanisms of action, pharmacokinetics and toxicity profile. Drug
Saf. 29:209–230. 2006. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Zhang J, Zhou CS, Liu S, Chen H and Yang
C: Effect of podophyllotoxin on human gastric cancer cell line SGC
7901. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 33:718–722. 2008.(In
Chinese).
|
|
10
|
Martin LJ: The mitochondrial permeability
transition pore: a molecular target for amyotrophic lateral
sclerosis therapy. Biochim Biophys Acta. 1802:186–197. 2010.
View Article : Google Scholar : PubMed/NCBI
|
|
11
|
Lemeshko VV: Potential-dependent membrane
permeabilization and mitochondrial aggregation caused by anticancer
polyarginine-KLA peptides. Arch Biochem Biophys. 493:213–220. 2010.
View Article : Google Scholar : PubMed/NCBI
|
|
12
|
Scorrano L: Opening the doors to
cytochrome c: changes in mitochondrial shape and apoptosis. Int J
Biochem Cell Biol. 41:1875–1883. 2010. View Article : Google Scholar : PubMed/NCBI
|
|
13
|
dos Santos AB, Dorta DJ, Pestana CR, et
al: Dehydromonocrotaline induces cyclosporine A-insensitive
mitochondrial permeability transition/cytochrome c release.
Toxicon. 54:16–22. 2009.PubMed/NCBI
|
|
14
|
Lee HJ, Lee HJ, Lee EO, et al:
Mitochondria-cytochrome c caspase-9 cascade mediates
isorhamnetin-induced apoptosis. Cancer Lett. 270:342–353. 2008.
View Article : Google Scholar : PubMed/NCBI
|
