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, Allal; Gaur, Rajiv Lochan; Abdraboh, Mohamed; Ireland, Shubha K.; Rao, Prakash N; Raj, Shailaja G; Al-Riyami, Hamad; Shanmuganathan, Somya; Gupta, Ishita; Murthy, Subramanyam N; Hollenbach, Andrew; Raj, Madhwa HG

doi:10.7150/jca.7235

International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

open access Global reach, higher impact

Full Text | PDF

J Cancer 2013; 4(9):703-715. doi:10.7150/jca.7235 This issue Cite

Research Paper

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

Allal Ouhtit^1,2*, Rajiv Lochan Gaur^1,3*, Mohamed Abdraboh^1,4*, Shubha K. Ireland^5*, Prakash N Rao⁶, Shailaja G Raj⁷, Hamad Al-Riyami², Somya Shanmuganathan², Ishita Gupta², Subramanyam N Murthy⁸, Andrew Hollenbach⁹, Madhwa HG Raj^1,10✉

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;
3. Present address: Department of Pathology, Stanford University, California.
4. Present address: Faculty of Science, University of Mansora, Egypt
5. Department of Biology, Xavier University of Louisiana, New Orleans, Louisiana.
6. New Jersey Organ and Tissue Sharing Network, New Jersey.
7. Protegene Corporation, Metairie, Louisiana.
8. Departnent of Environmental Toxicology, Southern University and A & M College, Baton Rouge, Louisiana,
9. Department of Genetics, LSU Health Sciences Center, New Orleans, Louisiana, USA,
10. Department of Obstetrics & Gynecology, Louisiana Health Sciences Center.
* These four authors equally contributed to this work.

Citation:

Ouhtit A, Gaur RL, Abdraboh M, Ireland SK, Rao PN, Raj SG, Al-Riyami H, Shanmuganathan S, Gupta I, Murthy SN, Hollenbach A, Raj MHG. 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. J Cancer 2013; 4(9):703-715. doi:10.7150/jca.7235. https://www.jcancer.org/v04p0703.htm

Other styles

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.

Keywords: Breast cancer, phytochemicals, chemoprevention, microarray, metastasis

Citation styles

APA

Ouhtit, A., Gaur, R.L., Abdraboh, M., Ireland, S.K., Rao, P.N., Raj, S.G., Al-Riyami, H., Shanmuganathan, S., Gupta, I., Murthy, S.N., Hollenbach, A., Raj, M.HG. (2013). 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. Journal of Cancer, 4(9), 703-715. https://doi.org/10.7150/jca.7235.

ACS

Ouhtit, A.; Gaur, R.L.; Abdraboh, M.; Ireland, S.K.; Rao, P.N.; Raj, S.G.; Al-Riyami, H.; Shanmuganathan, S.; Gupta, I.; Murthy, S.N.; Hollenbach, A.; Raj, M.HG. 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. J. Cancer 2013, 4 (9), 703-715. DOI: 10.7150/jca.7235.

NLM

CSE

Ouhtit A, Gaur RL, Abdraboh M, Ireland SK, Rao PN, Raj SG, Al-Riyami H, Shanmuganathan S, Gupta I, Murthy SN, Hollenbach A, Raj MHG. 2013. 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. J Cancer. 4(9):703-715.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.