The Role of Nutraceuticals in Chemoprevention and Chemotherapy and Their Clinical Outcomes

Table 4

Assessment of the chemotherapeutic and chemopreventive effects of nutraceuticals in combination studies.

Combination of nutraceutical	Dose used	Pathways affected or mechanistic action	Organ of study	Phase of study	Model of study	Reference
Curcumin + paclitaxel	50 μM/L + 10–50 μM/L based on the gene assessed	Inactivation of NF-κB and other metastatic genes.	Breast	In vitro	Human breast cancer cells MDA-MB-435	[63]
Curcumin + paclitaxel	2% w/w; 10 mg/kg	Inhibition of metastasis		In vivo	Human breast cancer xenograft model
Curcumin + xanthorrhizol	Synergistic effect in the range from 5 to 20 μg/mL	Induction of apoptosis	Breast	In vitro	Human breast MDA-MB-231 cancer cells	[64]
Curcumin + docosahexenic acid	Ratio of DHA to CCM; MCF-7; 55 : 30 μM; MCF10A; 95 : 45 μM; MDA-MB 35 : 35 μM; SK-BR-3; 60 : 40 μM; MDA-MB 50 : 25 μM	Inhibition of proliferation, more synergistic in one of the 5 cell lines tested.; Enhanced uptake of curcumin by the cells.; Upregulated genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion.; Downregulated genes involved in metstasis and invasion.	Breast	In vitro	Human breast cancer cells SK-BR-3, MDA-MB-231, MDA-MB-361, MCF-7, and MCF10AT	[65]
Curcumin + genistein	10 μM + 25 μM	Change in cell morphology and growth inhibition	Breast	In vitro	T47D and	[66]
	10 μM +25 μM				MCF-7
	11 μM + 25 μM				MDA-MB-231
Curcumin + sulphinosine	15 μM + 10 μM	Alter multidrug resistance genes.	Lung	In vitro	NCI-H460/R	[67]
		Alters the cell cycle with cells inhibited primarily in the S G2/M phase of the cycle
Curcumin + celecoxib	10–15 μM/L + 5 μM/L	Inhibition of cell proliferation and induction of apoptosis.	Colon	In vitro	HT-29	[68]
		Possible inhibition of Cox-2 pathways or through non-Cox-2 pathways			IEC-18-K-ras (Cox-2, high levels) Caco-2 (COX-2, low levels), and SW-480 (no COX-2)
Coltect + 5-aminosalicylic acid (ASA)	Coltect only 20 μM	Inhibition of tumor growth by induction of apoptosis.	Colon	In vitro	HT-29 cells	[69]
	150 mg/kg + 50 mg/kg	Inhibits abnormal crypt formation		In vivo	Chemical induction of tumors by 1,2-dimethyl; hydrazine (DMH) model in rats.
Curcumin + PEITC	25 μM + 10 μM	Additive effectives in the induction of apoptosis.	Prostate	In vitro	PC-3 C4 cell line	[27]
	3 μM + 2.5 μM	Inhibition of tumor growth through inhibition of Akt and NF-κB pathways.		In vivo	NCr-immunodeficient (nu/nu) mice bearing s.c. xenografts of PC-3; human prostate cancer cells	[70]
Pure 3—curcumin + resveratrol + EGCG;	Individual compounds, Percentage composition in the diet not defined	Inhibit growth by inhibiting hedgehog signaling pathways.	Prostate	In vitro	PC-3, LnCaP and mouse cell line TRAMP-C2	[71]
Pure 4—apigenin + baicalein + genistein + quercetin; Pure 7—Pure 3 + Pure 4; Crude 7—soy + sencha leaves + turmeric + yucca roots + saw palmetto + chamomile flowers + gingko		Reduce or delay the onset of tumors.		In vivo	Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice
D-Limonene + docetaxcel	0.2 mM + 1.9 nM	Induction of apoptosis by the regulation of proteins involved in mitochondrial apoptotic pathways	Prostate	In vitro	Human prostate carcinoma DU-145 and normal prostate epithelial PZ-HPV-7 cells	[72]
Tomato powder + broccoli powder; (10 : 10) g/100 g of diet	11 nM of lycopene per g of diet and broccoli powder,; 1.6 μM of glucoraphanin, 5.9 μM of glucobrassicin, 3.9 μM of gluconasturtiin, and 2.1 μM of neoglucobrassicin.	Reduction of tumor growth mediated by reduced cell proliferation and induction of apoptosis	Prostate	In vivo	Dunning R3327-H prostate adenocarcinoma model	[73]
Lycopene + ketosamine (fructose/amino acid Fru/His)	1 μM/L + 2 mM/L	Synergistic effect in inhibiting cell proliferation mediated processes. Antioxidant activity to prevent initiation of tumors.	Prostate	In vitro	Mat-Lylu rat cells	[74]
	20 μM/L + 5.6 mM/L	Reduce tumor growth and volume.		In vivo	Subcutaneous injections of Mat-Lylu cells in male Copenhagen rats
Lycopene + docetaxel	1 μM + 1 nM	Synergistically enhances the antiproliferative effects of docetaxel.	Prostate	In vitro	Human PC-3, LnCaP, DU145 cells	[75]
	15 mg/kg lycopene + 10 mg/kg docetaxel	Reduced tumor volume and growth by affecting the levels of IG-FR receptor that is highly expressed in a majority of prostate tumors. Inhibited Akt signaling and suppressed surviving necessary for tumor growth		In vivo	Xenograft of DU145 cells in NCR-nu/nu (nude) mice
Quercetin chalcone (QC) and a pH-modified citrus pectin (MCP)	1.6 mg/mL + 1.6 mg/mL	Reduction in the growth of solid primary tumors	Colon	In vivo	Balb/c mice	[76]
Quercetin + EGCG	20 μM + 0–60 μM	Inhibits the self renewal capacity of prostate cancer stem cells (PCSCs) by synergistically inducing apoptosis decreasing cell viability in spheroids, cell migration, invasion and colony formation	Prostate	In vitro	Prostate cancer stem cells (PCSCs)	[31]
Resveratrol + estrogen (E2)	10 μM + 1 nM	Antagonistic estrogenic effects in suppression of progesterone receptor	Breast	In vitro	Human MCF-7 cells	[39]
Resveratrol + quercetin + catechin	Either all at 0.5 μM and; 5 μM, or 20 μM	Synergistically inhibited cell proliferation and induced apoptosis.	Breast	In vitro	Human MDA-MB-231 cells	[77]
		Inhibited cell cycle progression with predominat cell cycle arrest in the G2 phase
	0.5, 5, and 25 mg/kg body weight in a 100-μL volume	Reduced primary tumor growth and, therefore, inhibit tumor progression		In vivo	Breast cancer xenografts in mouse models
Resveratrol + cyclophosphamide	50 μM + 5 mM	Inhibit cell proliferation via capase mediated cytotoxicity.; Enhanced proapoptotic genes Bax, Fas and suppressed anti apoptotic gene Bcl-2	Breast	In vitro	MCF-7	[78]
Resveratrol + n-Butyrate	50 μM + 2 mM/L	Inhibited cell proliferation and induced differentiation.; Attentuated p27 (Kip1) levels but enhanced p21 (Waf1/Cip1) expression.	Colon	In vitro	Caco-2	[79]
Resveratrol + 5-Fluorouracil	200 μM + IC50 800 μM	Inhibited cell proliferation and induced apoptosis by increase in capase 6 activity	Colon	In vitro	HCT116 p53 and p53	[80]
Resveratrol + genistein	250 mg/kg each in the AIN-76 diet	Suppressed prostate cancer development and mediated apoptosis by affecting the expression of steroid-receptor coactivor-3 and insulin-like growth factor-1	Prostate	In vivo	Simian Virus-40 T-antigen-(SV-40 Tag-) targeted probasin promoter rat model, a transgenic model of spontaneously developing prostate cancer.	[81]
Genistein + sulforaphane	5 μM/L + 15 μM/L	Affected DNA methyltransferase activity and reversed the gene expression of promoter hypermethylated genes of retinoic acid receptor h (RARb), RARB, p16INK4a p16 and O6-methylguanine methyltransferase enhanced growth inhibitory effects	Esophagous	In vitro	KYSE 510 cells	[82]
Sulforaphane + benzylisothio-; cyanite	10 μM + 10 μM	Changed cell morphology and inhibited cell proliferation.; Reduced cell viability that correlated with reduced pSTAT3 levels and an increase in PARP Cleavage	Pancreas	In vitro	PANC-1 cells	[83]
Sulforaphane + apigenin	10 μM + 10 μM	Synergistically induced phase II enzyme UDP-glucoronyl transferases (UGT1A1) transcript but to a lesser effect the protein level. Mediates this action by the induction of NF-κB	Colon	In vitro	CaCo-2	[84]
Sulforaphane + 3,3′-diindolylmethane (DIM)	2.5 μM + 20 μM	Has an antagonistic effect at low concentration on cell growth.	Colon	In vitro	Human colon cancer 40–16 cell line randomly derived from HCT116 clone	[85]
	Total concentration 40 μM	At cytotoxic concentrations of the compounds has synergistic effects on growth inhibition
Sulforaphane + dibenzoymethane (DMB)	AIN-76A diet supplemented with 300 ppm SFN and 0.5% DMB	Blocked colon tumor development	Colon	In vivo	Male Apc/^min + mice	[28]