Grape seed proanthocyanidins induce apoptosis through the mitochondrial pathway in nasopharyngeal carcinoma CNE-2 cells.
Although modern radiotherapy offers excellent local control in the treatment of nasopharyngeal carcinoma (NPC), current therapeutic decisions remain burdensome due to the frequency of local recurrence and treatment failure at distant sites. One potential and promising strategy for the prevention or treatment of cancers is the use of bioactive components of plant origin, including dietary plant products. Herein, we studied one class of these bioactive compounds, grape seed proanthocyanidins (GSPs), and explored their effect on NPC CNE-2 cells, as well as the primary mechanism underlying this effect. Our results revealed that treatment of human NPC CNE-2 cells with GSPs reduced cell viability in a dose- and time-dependent manner, and moreover, markedly induced cell cycle arrest at the G2/M phase, leading to induction of apoptosis. In addition, we found that the underlying mechanism was associated with increased expression of the pro-apoptotic protein Bax, decreased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PRAP) protein, and the loss of mitochondrial membrane potential (MMP) (Δψm). Furthermore, GSPs upregulated the Bcl-2 homology 3 (BH3)-only proteins, Bim and Bad, in a concentration-dependent manner. Taken together, these data supported our hypothesis that, in human NPC CNE-2 cells, GSPs could induce apoptosis through the mitochondrial pathway and ultimately reduce cell viability. Collectively, the results discussed above provide substantive evidence for the potential of GSPs as an effective bioactive phytochemical for the treatment of NPC.
Department of Otolaryngology of The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Kai
K
Yao
Institute of Biochemistry and Molecular Biology, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China.
Jingjing
J
Shao
Institute of Biochemistry and Molecular Biology, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China.
Keyuan
K
Zhou
Department of Otolaryngology of The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Haitao
H
Qiu
Department of Otolaryngology of The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Fengxiang
F
Cao
Institute of Biochemistry and Molecular Biology, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China.
Caihong
C
Li
Department of Otolaryngology of The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
De
D
Dai
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3