Naringenin-Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways

Whasun Lim, Sunwoo Park, Fuller W. Bazer, Gwonhwa Song

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Prostate cancer is the most common cancer in men and the second most common cause of cancer-related deaths in men. Although, various drugs targeting the androgen receptor are normally used, the patients frequently undergo recurrence of the disease. To overcome these limitations, natural compounds have been researched for evidence that they suppress progression and metastasis of various cancer cells. In the present study, we investigated effects of naringenin, a natural anti-oxidant flavonoid derived from citrus, on prostate cancer cells (PC3 and LNCaP). Results of present study with PC3 and LNCaP cells revealed that naringenin inhibited proliferation and migration, while inducing apoptosis and ROS production by those cells. In addition, naringenin-induced loss of mitochondrial membrane potential and increased Bax and decreased Bcl-2 proteins in PC3 cells, but not LNCaP cells. In a dose-dependent manner, naringenin decreased phosphorylation of ERK1/2, P70S6K, S6, and P38 in PC3 cells, and reduced phosphorylation of ERK1/2, P53, P38, and JNK proteins in LNCaP cells. However, naringenin activated phosphorylation of AKT in both PC3 and LNCaP cells. Then, targeted signaling proteins associated with viability of PC3 and LNCaP cells were analyzed using pharmacological inhibitors of AKT and ERK1/2 cell signaling pathways. Moreover, we compared the apoptotic effects of naringenin and paclitaxel alone and in combination to find that naringenin enhanced the efficiency of paclitaxel to suppress progression of prostate cancer cell lines. Collectively, these results indicate that naringenin is a potential chemotherapeutic agent for treatment of prostate cancer. J. Cell. Biochem. 118: 1118–1131, 2017.

Original languageEnglish
Pages (from-to)1118-1131
Number of pages14
JournalJournal of Cellular Biochemistry
Volume118
Issue number5
DOIs
Publication statusPublished - 2017 May 1

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Cell death
Phosphatidylinositol 3-Kinases
Prostatic Neoplasms
Cell Death
Cells
Phosphorylation
Paclitaxel
Cell signaling
70-kDa Ribosomal Protein S6 Kinases
Proteins
naringenin
Androgen Receptors
Flavonoids
Oxidants
S 6
Neoplasms
Citrus
Mitochondrial Membrane Potential
Drug Delivery Systems
Apoptosis

Keywords

  • APOPTOSIS
  • MITOCHONDRIA
  • NARINGENIN
  • PROSTATE CANCER
  • SIGNALING PATHWAY

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Naringenin-Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways. / Lim, Whasun; Park, Sunwoo; Bazer, Fuller W.; Song, Gwonhwa.

In: Journal of Cellular Biochemistry, Vol. 118, No. 5, 01.05.2017, p. 1118-1131.

Research output: Contribution to journalArticle

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