World J Mens Health.  2014 Aug;32(2):76-82. 10.5534/wjmh.2014.32.2.76.

A Milk Protein, Casein, as a Proliferation Promoting Factor in Prostate Cancer Cells

• Park SW
• Kim JY
• Kim YS
• Lee SJ
• Lee SD
• Chung MK

• KMID: 2320796
• DOI: http://doi.org/10.5534/wjmh.2014.32.2.76

Abstract

PURPOSE
Despite most epidemiologic studies reporting that an increase in milk intake affects the growth of prostate cancer, the results of experimental studies are not consistent. In this study, we investigated the proliferation of prostate cancer cells treated with casein, the main protein in milk.
MATERIALS AND METHODS
Prostate cancer cells (LNCaP and PC3), lung cancer cells (A459), stomach cancer cells (SNU484), breast cancer cells (MCF7), immortalized human embryonic kidney cells (HEK293), and immortalized normal prostate cells (RWPE1) were treated with either 0.1 or 1 mg/mL of alpha-casein and total casein extracted from bovine milk. Treatments were carried out in serum-free media for 72 hours. The proliferation of each cell line was evaluated by an 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.
RESULTS
alpha-Casein and total casein did not affect the proliferations of RWPE1, HEK293, A459, SNU484, MCF7, HEK293, or RWPE1 cells. However, PC3 cells treated with 1 mg/mL of alpha-casein and casein showed increased proliferation (228% and 166%, respectively), and the proliferation of LNCaP cells was also enhanced by 134% and 142%, respectively. The proliferation mechanism of alpha-casein in PC3 and LNCaP cells did not appear to be related to the induction of Insulin-like growth factor-1 (IGF-1), since the level of IGF-1 did not change upon the supplementation of casein.
CONCLUSIONS
The milk protein, casein, promotes the proliferation of prostate cancer cells such as PC3 and LNCaP.

Keyword

Caseins; Cell proliferation; Milk; Neoplasms; Prostate

MeSH Terms

Breast Neoplasms
Caseins*
Cell Line
Cell Proliferation
Culture Media, Serum-Free
Humans
Insulin-Like Growth Factor I
Kidney
Lung Neoplasms
Milk
Milk Proteins*
Prostate
Prostatic Neoplasms*
Stomach Neoplasms
Caseins
Culture Media, Serum-Free
Insulin-Like Growth Factor I
Milk Proteins

Figure

• 

  Fig. 1 Growth induction of casein and α-casein on proliferation of PC-3 cells. Cell survival was determined using 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. (A) Percentage of surviving cells versus control group under serum conditions for 2 to 3 days. (B) Percentage of surviving cells versus control group under serum-free conditions for 2 to 3 days. Data are presented as the mean value (n=36 in each cell). ap<0.05, bp<0.001 versus control responses.

• 

  Fig. 2 Casein can promote proliferation of prostate cancer cells. Prostate cancer cells (PC-3 and LNCaP) proliferated at an increased rate with α-casein supplementation under serum-free conditions. However, other cancer cells did not show any differences as compared to an untreated group. ap<0.05, bp<0.001 versus control responses.

• 

  Fig. 3 The effects of α-casein and casein on morphology. The morphological changes of various cells were observed by light microscopy after treatment with α-casein and casein under serum-free conditions for 72 hours. Under control conditions (vehicle: NaOH), PC-3 cells appeared to have a typical phenotype, featured with round nuclei and homogeneity. (A) After treatment with casein (or α-casein), PC-3 cells showed the following different morphological changes: 1) increase in cell volume, 2) more cohesion, and 3) marked increase in cell number. (B) Likewise, LNCaP cells showed increased cellular adhesion. (C) Treated MCF7 cells showed no morphological changes as compared to the untreated cells. (D) RWPE-1 cells also showed an increase in cellular adhesion without the changes in cell volume and number.

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