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Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action.

Ouhtit A, Gaur RL, Abdraboh M, Ireland SK, Rao PN, Raj SG, Al-Riyami H, Shanmuganathan S, Gupta I, Murthy SN, Hollenbach A, Raj MH - J Cancer (2013)

Bottom Line: Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects.The compounds were ineffective individually.In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death.

View Article: PubMed Central - PubMed

Affiliation: 1. Stanley S Scott Cancer Center, Louisiana Health Sciences Center, New Orleans, Louisiana. ; 2. Present address: Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Oman;

ABSTRACT
Traditional chemotherapy and radiotherapy for cancer treatment face serious challenges such as drug resistance and toxic side effects. Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects. We hypothesized that a super combination (SC) of known phytochemicals used at bioavailable levels could induce 100% killing of breast cancer (BC) cells without toxic effects on normal cells and that microarray analysis would identify potential genes for targeted therapy of BC. Mesenchymal Stems cells (MSC, control) and two BC cell lines were treated with six well established pro-apoptotic phytochemicals individually and in combination (super cocktail), at bioavailable levels. The compounds were ineffective individually. In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death. However, there were no deleterious effects on MSC cells used as control. Furthermore, the SC down-regulated the expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell factor) in the BC cell lines. Microarray analysis revealed several differentially expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC-promoted BC cell death and motility. Four unique genes were highly up-regulated (ARC, GADD45B, MYLIP and CDKN1C). This investigation indicates the potential for development of a highly effective phytochemical combination for breast cancer chemoprevention / chemotherapy. The novel over-expressed genes hold the potential for development as markers to follow efficacy of therapy.

No MeSH data available.


Related in: MedlinePlus

Effect of the phytochemical combination on MCF7 and MDA-MB-231 cell morphology. MCF7 and MDA-MB-231 cells at day 0 exhibited a smooth epithelial cell pattern with prominent nuclei. In contrast the cells treated with the 6-combination start to lose cell-cell contact and attain more rounded shape at day 1. By day 2, cells cluster together, demonstrate membrane blebbing, and start to detach from the dish (original magnification, X100).
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Figure 2: Effect of the phytochemical combination on MCF7 and MDA-MB-231 cell morphology. MCF7 and MDA-MB-231 cells at day 0 exhibited a smooth epithelial cell pattern with prominent nuclei. In contrast the cells treated with the 6-combination start to lose cell-cell contact and attain more rounded shape at day 1. By day 2, cells cluster together, demonstrate membrane blebbing, and start to detach from the dish (original magnification, X100).

Mentions: In order to determine whether cell death contributed to these observed effects on proliferation, we examined the cellular morphology of MCF7 and MDA-MB-231 BC cells on day 1 and day 2 of 6-combination treatment using phase contrast microscopy. MCF7 and MDA-MB-231 cells exhibited a smooth epithelial cell pattern with prominent nuclei on day 0 of experiment (before treatment). In contrast both MCF7 and MDA-MB-231 cells treated with the 6-combination started to lose cell-cell contact after 24 h. After 48 h the cells detached from the surface of the tissue culture dish, indicating the cell death (Figure 2).


Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action.

Ouhtit A, Gaur RL, Abdraboh M, Ireland SK, Rao PN, Raj SG, Al-Riyami H, Shanmuganathan S, Gupta I, Murthy SN, Hollenbach A, Raj MH - J Cancer (2013)

Effect of the phytochemical combination on MCF7 and MDA-MB-231 cell morphology. MCF7 and MDA-MB-231 cells at day 0 exhibited a smooth epithelial cell pattern with prominent nuclei. In contrast the cells treated with the 6-combination start to lose cell-cell contact and attain more rounded shape at day 1. By day 2, cells cluster together, demonstrate membrane blebbing, and start to detach from the dish (original magnification, X100).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3842439&req=5

Figure 2: Effect of the phytochemical combination on MCF7 and MDA-MB-231 cell morphology. MCF7 and MDA-MB-231 cells at day 0 exhibited a smooth epithelial cell pattern with prominent nuclei. In contrast the cells treated with the 6-combination start to lose cell-cell contact and attain more rounded shape at day 1. By day 2, cells cluster together, demonstrate membrane blebbing, and start to detach from the dish (original magnification, X100).
Mentions: In order to determine whether cell death contributed to these observed effects on proliferation, we examined the cellular morphology of MCF7 and MDA-MB-231 BC cells on day 1 and day 2 of 6-combination treatment using phase contrast microscopy. MCF7 and MDA-MB-231 cells exhibited a smooth epithelial cell pattern with prominent nuclei on day 0 of experiment (before treatment). In contrast both MCF7 and MDA-MB-231 cells treated with the 6-combination started to lose cell-cell contact after 24 h. After 48 h the cells detached from the surface of the tissue culture dish, indicating the cell death (Figure 2).

Bottom Line: Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects.The compounds were ineffective individually.In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death.

View Article: PubMed Central - PubMed

Affiliation: 1. Stanley S Scott Cancer Center, Louisiana Health Sciences Center, New Orleans, Louisiana. ; 2. Present address: Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Oman;

ABSTRACT
Traditional chemotherapy and radiotherapy for cancer treatment face serious challenges such as drug resistance and toxic side effects. Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects. We hypothesized that a super combination (SC) of known phytochemicals used at bioavailable levels could induce 100% killing of breast cancer (BC) cells without toxic effects on normal cells and that microarray analysis would identify potential genes for targeted therapy of BC. Mesenchymal Stems cells (MSC, control) and two BC cell lines were treated with six well established pro-apoptotic phytochemicals individually and in combination (super cocktail), at bioavailable levels. The compounds were ineffective individually. In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death. However, there were no deleterious effects on MSC cells used as control. Furthermore, the SC down-regulated the expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell factor) in the BC cell lines. Microarray analysis revealed several differentially expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC-promoted BC cell death and motility. Four unique genes were highly up-regulated (ARC, GADD45B, MYLIP and CDKN1C). This investigation indicates the potential for development of a highly effective phytochemical combination for breast cancer chemoprevention / chemotherapy. The novel over-expressed genes hold the potential for development as markers to follow efficacy of therapy.

No MeSH data available.


Related in: MedlinePlus