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

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.

Complementary/Alternative Medicine Strategies for Prevention and or Cure of Breast Cancer: A Review

“…In contrast to our studies in the rat, we observed that C-Phycocyanin treatment by itself did not inhibit proliferation of human breast cancer cells (MCF-7 and MDA-MB-231) over a 6 day period, at the dose used [20]. However, it was useful as part of a super cocktail of six phytochemicals in inhibiting proliferation of the human cancer cells, by participating in a synergistic reaction with the 5 other phytochemicals.…”

“…We extended this principal and hypothesized that combinations of several such bioactive compounds can be developed to a degree where the synergism results in the bioavailable levels becoming effective levels to kill 100% of cancer cells. We demonstrated this by combining 6 phytoantioxidants at their bioavailable levels and investigating their effects on breast cancer cells [20]. We chose six phytochemicals to be included in this combination of a 'super cocktail': Indole-3-carbinol (from broccoli), resveratrol (from grape seeds and skin), curcumin (from turmeric root), quercetin (from apple peel), C-phycocyanin (from spirulina) and genestin (from soy beans).…”

Kaempferol mediated synthesis of gold nanoparticles and their cytotoxic effects on MCF-7 cancer cell line

“…Presence of cells in sub-G1 phase after treatment with k-AuNPs for a period of 24 h indicate that apoptosis is induced at an earlier time period than in the presence of pure kaempferol. A combination of six phytochemicals has been shown to induce only 45.36 % of apoptosis in breast cancer cells [54]. On the other hand, in our study, the conjugation of a single phytochemical kaempferol to the AuNP core is found to induce apoptosis significantly.…”

Nordihydroguaiaretic acid ameliorates cisplatin induced nephrotoxicity and potentiates its anti-tumor activity in DMBA induced breast cancer in female Sprague–Dawley rats

“…Although conventional medicine has witnessed significant progress in the treatment of breast cancer, pharmacological interferences are uptight with their own endogenous complications, including many known and unknown legal and ethical issues [5]. Besides, breast cancer cells acquire resistance to chemotherapeutic drugs by means of different cell signaling mechanisms [6,7].…”