Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

Table 2

In  vitro studies of ginseng in combination with other anticancer drugs.

Ginseng products	Source	Cells	Conc.	Anticancer drugs	Direct action (cytotoxicity)	Indirect action	Reference
Panax ginseng extracts (RG and WG)	Tongrentang Pharmacy, Beijing, China; WG compared with RG: lower in Rg1, Rb1 and Rd; higher in Rg3.	HCT-116	100~300 𝜇g/mL	5-FU	HCT-116 (+): RG > WG	(1) Apoptosis induction: RG (−); (2) Cell cycle arrest: RG (G1 phase)	[15]
Panax ginseng extracts	Tongrentang Pharmacy, Beijing, China, major ginsenosides Rg1, Rb1, Rd	BIU-87, A549, SW480, BGC823	0.1–100 𝜇g/mL	5-FU	BGC823 (+); SW480 (−); A549 (−); BIU-873 (−)	None	[16]
Ginsenoside Panaxadiol	National Institute for the Control of Pharmaceutical and Biological; Products, Beijing, China	HCT-116, SW-480	10 𝜇M	Irinotecan	HCT-116 (+); SW-480 (+)	(1) Apoptosis induction; (2) Cell cycle arrest: G1 phase [17]/S phase [14]	[18]
		HCT-116	5~25 𝜇M	5-FU	HCT-116 (+)		[19]
Ginsenoside Panaxytriol	Red Panax ginseng, Nikkan Korai Ninjin, Kobe, Japan	MK-1	1~12.5 𝜇g/mL	mitomycin C	MK-1 (+)	Increase cellular drug accumulation (by decreasing membrane fluidity)	[20]
Ginsenoside Rg3	Korea ginseng: Sun ginseng	SW620, HCT116	25~100 𝜇M	Docetaxel; cisplatin; doxorubicin; paclitaxel	SW620 (+); HCT116 (+)	(1) Apoptosis induction; (2) Cell cycle arrest: G0/G1 phase; (3) Decrease drug resistant by inactivating NF-kappaB	[21]
		LNCaP, PC-3, DU145		Docetaxel; cisplatin; doxorubicin	LNCaP (+); PC-3 (+); DU145 (+)		[22]
Ginsenosides	Red Panax Ginseng	Leukemic progenitor cells	20 𝜇g/mL	Homoharringtonine cytarabine, adriamycin, and etoposide	Leukemic progenitor cells (+)	Stimulate progenitor cell proliferation by driving noncycling progenitors to enter cell cycle	[23]
Ginsenosides, Rh4 and Rk3 (unique ginsenosides of SG/RG)	Korean ginseng: WG: Korea local SG and RG: Ginseng Science Inc. Seoul, Korea	LLC-PK1	10~160 𝜇g/mL, Rh4/Rk3: 5~20 𝜇g/mL	Cisplatin	N/A	Reduce drug-induced renal injury: (i) increase cell viability: RG/Rh4/Rk3 (+), WG (−); (ii) decrease LDH leakage: Rh4/Rk3 (+)	[24]
Ginsenoside Rd	Self-prepared from Korean ginseng	LLC-PK1	25~125 𝜇M	cisplatin	N/A	Reduce drug-induced renal toxicity: (i) Decrease LDH leakage; (ii) Suppress apoptosis	[25]
Ginsenosides, protopanaxatriol ginsenosides (major Rg1, Re), protopanaxadiol ginsenosides (major Rb1, Rb2, and Rc)	Korean red ginseng: Korea Ginseng and Tobacco Research Institute, Taejeon, Korea	AML-2/D100 (overexpress Pgp),; AML-2/DX100 (overexpress MRP)	50~300 ug/mL	Daunorubicin	AML-2/D100: PTG (+), others (−)	Decrease drug resistant: inhibit Pgp activity (protopanaxatriol group)	[26]
Acidic polysaccharide	Korean red ginseng: Korea Ginseng Cooperation, Daejeon, Korea	BALB/C mouse splenocytes and macrophages	10–1000 𝜇g/mL	paclitaxel	N/A	Reduce drug-induced toxicity (immunosuppression): (i) restore splenocyte proliferation; (ii) increase macrophage cytotoxicity	[27]
Shengmai (Chinese herbal preparation consisting red ginseng, lilyturf root, and magnolia vine fruit)	China, no detailed description	A549, SGC-7901, MCF-7, HepG-2	30 𝜇g/mL	gemcitabine, cisplatin, paclitaxel, and epirubicin	A549 (+) SGC-7901 (+); MCF-7 (+); HepG-2 (+)	Decrease drug resistant: downregulating mRNA expression level of MDR-1.	[28]

Human bladder cancer cell line (BIU-87); human lung cancer cell line (A549); human colon cancer cell line (SW480); human gastric cancer cell line (BGC823, MK-1, and SGC-7901); human colorectal cancer cells (HCT-116, SW-480, and SW620); human prostate cancer cell lines (LNCaP, PC-3, DU145); human breast carcinoma (MCF-7), human hepatocellular carcinoma (HepG-2), pig renal tubular epithelial cells (LLC-PK₁), two resistant acute myelogenous leukemia (AML) sublines: daunorubicin- and doxorubicin-resistant AML-2 subline (AML-2/D100 and AML-2/DX100 overexpress Pgp and MRP, respectively); red ginseng (RG), white ginseng (WG); Sun ginseng (SG); p-glycoprotein (Pgp); multidrug resistance-associated protein (MRP); “+”: positive; “−”: negative.