Table 1.

Various reported combined systems incorporating flavonoid and synthetic anticancer agents. The literature has reported several pieces of evidence; however, we have summarized only the more recent instances of combinations of flavonoids with synthetic anticancer agents.

S. No	Flavonoid	Synthetic Anticancer Drug	Cancer Type	Result	Model	IC50 Value	Cell Type	Reference
1	Quercetin	5-Flurouracil	Esophageal	Inhibited the growth of EC9706 cells and induced higher apoptosis compared to 5-Flurouracil alone.	In vitro	QCN = 100 µM; 5-FU= 0.2 mM	EC9706; Eca109	[92]
2	Quercetin	5-Flurouracil	Colorectal	Combination of quercetin and 5-Flurouracil reduced the growth of HT29 cells significantly compared to quercetin alone.	In vitro	QCN = 176.6 µg/mL; 5-FU = 107 µg/mL	HT-29	[93]
3	Quercetin	Docetaxel	Prostate	Quercetin in combination with docetaxel reversed drug resistance via P13K/AkT signaling pathways.	In vitro	QCN = 20 µM; DTX = 5 nM	LNCaP/R; PC-3/R	[94]
4	Quercetin	Docetaxel	Breast	These two drugs in combination provided synergistic effects and resensitized the cancer cells to cancer treatment.	In vitro	QCN = 64.8 µM; DTX = 5 nM	MCF-7	[95]
5	Quercetin	Docetaxel	Hepatic	Demonstrated superior anticancer efficacy with accumulation in tumor cells.	In vitro; In vivo	DTX-QCN = 0.00639 µg/mL	HepG2	[96]
6	Quercetin	Vincristine	Breast	Provided synergistic anticancer effects by delivery of both compounds to the cancer cells.	In vitro	-	MCF-7	[97]
7	Quercetin	Gemcitabine	Pancreatic	Demonstrated enhanced cellular uptake and improved cytotoxicity towards cancer cells. Interestingly, in combination, these drugs showed better therapeutic effects.	In vitro	GMC = 0.97 µM; QCN = 97µM	Mia-PaCa-2; PANC-1	[98]
8	Quercetin	Methotrexate	Osteosarcoma	Quercetin increased methotrexate cytotoxicity in cancer cells.	In vitro	QCN = 142.3 µM; MTX = 13.7 ng/mL	Saos-2	[99]
9	Kaempferol	5-Flurouracil	Colon	Showed synergistic inhibitory effects with respect to cell cytotoxicity. In addition, both drugs induced apoptosis and initiated cell cycle arrest. The blockade of ROS production by kaempferol and the modulation of various proteins validated the success of chemotherapy.	In vitro	KMP = 44 µM; 5FU = 26 µM	LS174	[100]
10	Kaempferol	5-Flurouracil	Colorectal	Kaempferol reversed 5-Fluorouracil resistance by downregulating PKM2-mediated glycolysis.	In vitro	KMP = 70µM; 5FU = 37 µM	LS174	[101]
11	Kaempferol	Cisplatin	Head and Neck Squamous	The combination was shown to inhibit the consumption of oxygen and metabolism, and reduced the ATP content in cancer cells.	In vitro	KMP = 120 µM; 40 µM	Cal-27; Hep-2	[102]
12	EGCG	Docetaxel	Prostate	EGCG in combination with docetaxel reduced the resistance of docetaxel towards cancer cells and increased the chemotherapeutic effects.	In vitro	EGCG = 40 µM; DTX = 5 nM	LAPC-4-AI; PA-3	[103]
13	EGCG	5-Flurouracil	Colorectal	EGCG was revealed to improve the sensitivity of colorectal cells for 5-Flurouracil by inhibiting and downregulating the GRP78/NF-kB/miR-155-p/MDR1 pathway.	In vitro	5FU = 5 µM; EGCG= 50 µM	HCT-116; DLD1	[104]
14	EGCG	5-Flurouracil	Oral Squamous cell	It was revealed that this combination significantly reduced both cell viability and cell migration compared to 5-Flurouracil alone.	In vitro	-	PE/CA-PJ15	[105]
15	EGCG	Doxorubicin	Pancreatic; Colon	This combination significantly induced apoptosis and blocked cell metastasis and progression by downregulating the ERK pathway.	In vitro	EGCG = 62 µM; DOX = 5 µM	Panc-1; MIA PaCa-2; BxPc-3; HCT15	[106]
16	EGCG	Gemcitabine	Pancreatic	EGCG with gemcitabine was revealed to downregulate the growth, invasion, and migration of cancer cells, causing apoptosis by hampering the STAT3 signaling pathway.	In vitro	EGCG = 60µM; GCM = 20 µM	AsPC-1; PANC-1	[107]
17	EGCG	Docetaxel	Prostate	The combination of these two reduced the tumor growth by 62 fold.	In vivo	-	CRPC	[108]
18	Naringenin	Paclitaxel	Prostate	It was revealed that naringenin sensitized the cancer cells for paclitaxel therapy by inducing apoptosis and cell cycle arrest in the G1 phase.	In vitro	NGN = 150 µM; PTX = 5 nM	DU145; PC3	[109]
19	Naringenin	Cisplatin	Cervical	It was revealed that naringenin impaired cell growth by initiating apoptosis, proliferation, and cytotoxicity.	In vitro	NGN = 500 µM; CSP = 16 µM	HeLa	[110]
20	Naringenin	Cisplatin	Lung	In combination with naringenin, the chemotherapeutic effects of cisplatin were significantly increased, with naringenin increasing the expression of caspase-3, and recuing the expression of MMP-2, and MMP-9.	In vitro	CSP = 28 µL/mL; NGN = 200 µM	A549	[34]
21	Epicatechin	5-Flurouracil	Gastric	In combination, epicatechin showed higher inhibitory effects on the production of lactate and exhibited higher cytotoxicity and ROS-mediated apoptosis in SNU620/FU cells.	In vitro	-	SNU620	[111]
22	Epicatechin	Docetaxel	Prostate/Breast	Higher chemotherapeutic effects were observed through the upregulation of CDKN1A, BAX, and caspase 9.	In vitro	-	PC3; DU-145; MCF-7	[112]
23	Epicatechin	Cisplatin	Lung	Epicatechin showed concentration-dependent cytotoxicity with cisplatin and promoted cell death by a exerting synergistic effect.	In vitro	-	A549/DDP	[113]
24	Epicatechin	Doxorubicin	Breast	In combination with doxorubicin, epicatechin reduced the chances of cardiotoxicity without altering the chemotherapeutic effects of doxorubicin in MDA-MB231 cells.	In vitro; In vivo	-	MCF-7; T47D; MDA-MB-231	[114]