Dihydromyricetin Acts as a Potential Redox Balance Mediator in Cancer Chemoprevention

Table 1

The chemopreventive effect and potential mechanism of dihydromyricetin in cancer.

Origin	Cell lines/animals/human	Treatment methods	Mode of administration	Dose and duration time	Mechanism of action/activities/effects showed	Reference
DHM prepared from A. grossedentata with a purity of 98%	Osteosarcoma cells	Cell cycle and apoptosis analysis		15, 30, and 60 μM for 24 or 48 h	(1) Exhibited anticancer activity through increased p21 expression and G2-M cell cycle arrest, caused DNA damage, activated ATM-CHK2-H2AX signaling pathways, and induced apoptosis in osteosarcoma cells; (2) Antitumor could be due to the activation of AMPK and p38MAPK pathways	Zhiqiang et al. (2014)
	Non-small-cell lung cancer (NSCLC) cells	Cell death analysis		20 μM for 48-72 h	DHM in combination with erlotinib induced cell death via the NOX2-ROS-Bim pathway in NSCLC cells	Seung-Woo et al. (2017)
Ampelopsins A and C isolated from the roots of V. thunbergii with a purity of 98.5 and 99.0%, respectively	MDA-MB-231 breast cancer cells	Metastasis analysis		Ampelopsin A (10−50 μM) and Ampelopsin C (1−5 μM) for 24−72 h	Inhibited metastasis of MDA-MB-231 cells by downregulating the AxL, TYRO3, and FYN expressions	Cheng et al. (2019)
	MCF-7 and MDA-MB-231 breast cancer cells	Cell viability and increased apoptosis analysis		60 μM for 24 h	DHM inhibited cell viability and increased apoptosis in MCF-7 and MDA-MB-231 breast cancer cells through ROS generation and ER stress pathway	Yong et al. (2014)
Ampelopsin (purity not provided)	HepG2 cells	Apoptosis analysis		0, 12.5, 25, 50, 100, 150, and 200 μg/mL for 12, 24, and 36 h	(1) Induced apoptosis of HepG2 cells; (2) Enhanced the levels of death receptor 4 (DR4) and death receptor 5 (DR5) and reduced the expression of Bcl-2 protein	Shimei et al. (2015)
	A549 human adenocarcinoma lung epithelial cells	Apoptosis analysis		0, 10, 20, or 30 μM for 48 h	(1) Induced apoptosis in A549 cells; (2) Reduced Bcl 2 and increased Bax levels; (3) Cleaved PARP and reduced XIAP and survivin expression levels; (4) Cleaved poly(ADP-ribose) polymerase expression	Xin-mei et al. (2015)
	Mouse hepatocellular carcinoma cells (Hepal-6)	Cell viability and apoptosis analysis		10, 50, or 100 μM for 6 h, 12 h, and 24 h	DHM inhibited cell viability and induced apoptosis by downregulating ROS production via the TGF β/Smad3 signaling pathway in Hepal 6 cells	Bin et al. (2015)
AMP extracted from A. megalophylla (purity not provided)	HeLa cells	Apoptosis analysis		0, 30, 40, 50, 60, or 70 μM for 8 h or 12 h	Induced apoptosis in HeLa cells through activation of caspases 9 and 3	Peipei et al. (2017)
	Hepatoma cell lines SK-Hep-1 and MHCC97L	Growth inhibition assays		0, 10, 50, and 100 μmol/L for 24 h	DHM inhibited the migration and invasion of hepatoma cells via reducing the phosphorylation levels of p38, ERK1/2, and JNK	Qing-Yu et al. (2014)
DHM with a purity of 95%	HepG2 cells	Apoptosis analysis		0, 10, 20, and 30 μM for 24 h	(1) Inhibition of the Akt/Bad signaling pathway; (2) Upregulated the levels of mitochondrial proapoptotic proteins Bax and Bad; (3) Inhibited the expression of the antiapoptotic protein Bcl-2 and enhanced the cleavage and activation of caspase 3; (4) Degradation of poly(ADP-ribose) polymerase	Zhuangwei et al. (2017)
	Human melanoma SK-MEL-28 cells	Cell cycle and apoptosis analysis		0, 50, and 100 μM for 24, 48, or 72 h	(1) DHM inhibited cell proliferation (SK-MEL-28) cells through cell cycle arrest at the G1/S phase; (2) Increased the production of p53 and p21 and downregulated the Cdc25A, Cdc2, and P-Cdc2 proteins; (3) Induced apoptosis through enhancing the expression levels of Bax proteins and decreasing the protein levels of IKK-α, NF-κB (p65), and P-p38	Guofang et al. (2014)
	AGS human gastric cancer cells	Cytotoxicity assays		25, 50, and 100 μM for 48 or 72 h	DHM inhibited AGS cell proliferation and induced cell cytotoxicity through the regulation of expression of apoptotic genes such as p53 and B-cell lymphoma-2	Ji et al. (2015)
	HepG2 cells	Cell growth inhibition assays		5, 10, 25, and 50 μM for 6, 12, 24, and 48 h	DHM-induced autophagy inhibited cell proliferation through suppressing the activation of mTOR and regulating upstream signaling pathways such as ERK1/2, AMPK, and PI3K/PDK1/Akt pathways	Juan et al. (2014)
	Human choriocarcinoma cell line (JAr cells)	Apoptosis assays		0, 40, 60, and 100 mg/L for 48 h	Inhibited proliferation of JAr cells by inducing apoptosis through increasing protein expression level of BCL-2 associated X, and associated protein, and decreased the levels of BCL-2 and procaspase 3	Yanzhen et al. (2018)
DHM (purity not provided)	Human ovarian cancer A2780 and SKOV3 cells	Apoptosis assays		25, 50, and 100 μM for 24 or 48 h	DHM inhibited the ovarian cancer cells and induced cell apoptosis through p53-mediated downregulation of survivin	Yingqi et al. (2017)
	HepG2, QGY7701, QGY7703, Huh 7, QSG7701, MHCC97L and H, and SK-Hep-1 cells	Cell proliferation and apoptosis assays		0, 50, and 100 μM for 24, or 48 h	(1) DHM inhibited cell proliferation and induced cell apoptosis in hepatocellular carcinoma cells; (2) Apoptosis was induced through upregulating p53 expression, and the upregulation of p53 increased the levels of cleaved-caspase 3 protein	Jie et al. (2014)
	SK-MEL-28 human melanoma cells	Apoptosis		25, 50, and, 100 μM for 24 h	Enhanced cell death and apoptosis by regulating the NF-κB signaling pathway	Ding-Zhou et al. (2017)
	Hepatocellular carcinoma cells	Apoptosis		25-200 μM for 12 or 24 h	DHM with Nedaplatin (NDP) inhibited growth and induced apoptosis through the activation of the p53/Bcl-2 signaling pathways	Lianggui et al. (2015)
	A549 lung carcinoma cells and fibroblasts	Growth inhibition assays		0, 1, 5, and 10 μM for 48 h	DHM inhibited the growth of fibroblasts in the lung cancer cells via the activation of Erk1/2 and Akt signaling pathways	Kai-jie et al. (2017)
	Hepatocellular cancer cells (HepG2 and Hep3B)	Growth inhibition and cell cycle assays		2, 10, 50, 100, and 200 μM for 48 h	Inhibited proliferation of the cells via G2/M phase cell cycle arrest through the Chk1/Chk2/Cdc25C signaling pathway	Haili et al. (2013)
	Human choriocarcinoma JAR cells	Growth inhibition and cell cycle assays		0, 40, 60, and 100 mg/L for 48 h	DHM inhibited the proliferation of JAR cells through cell cycle arrest via the downregulation of cyclin A1, cyclin D1, SMAD3, and SMAD4 expression levels	Yanzhen et al. (2020)
	Human ovarian cancer SKOV3 cells	Cell migration, invasion, and apoptosis assays		80 and 120 μM for 48 h	(1) Exhibited anticancer activity by reducing cell migration and invasion; (2) Induced cell apoptosis via upregulation of cleaved-caspase 3 and the Bax/Bcl-2 ratio; (3) Inhibited GRASP65 expression and the regulation of the JNK/ERK pathway	Fengjie et al. (2019)
DHM 98%	Human non-small-cell lung cancer (A549 and H1975) cell lines	Cytotoxic and apoptosis assays		0, 50, 75, and 100 μM for 24 h	Exhibited cytotoxic effect by inducing apoptosis through Bcl-w suppression-mediated mitochondrial membrane depolarization, caspase 9/7/3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in A549 and H1975 cells	Shang-Jyh et al. (2017)
DHM (purity not provided)	Human gastric carcinoma cells (SGC7901 and SGC7901/5-FU)	Proliferation inhibition assays		1.25 and 2.5 μg/mL for 48 h	Inhibited proliferation of both SGC7901 and SGC7901/5-FU cells through the downregulation of the MDR1 expression	Mingcai et al. (2020)
	Human hepatocarcinoma (HepG2) cells	Apoptosis assays		10, 50, and 100 μM for 24 h	DHM-induced apoptosis of human hepatocellular carcinoma cells through a ROS-related pathway	Bin et al. (2014)
Ampelopsin (purity not provided)	Breast cancer MDA-MB-231 cells and rats	MNU-induced breast cancer in rats	Orally fed	10, 25, 50 μM for 48 h and 50 and 100 mg/kg BW for 18 weeks	Inhibited the cancer cells effectively in vitro and in vivo through effectively suppressing mammalian target of rapamycin (mTOR) activity in breast cancer	Chang et al. (2014)
Ampelopsis isolated from A. grossedentata with 80%	PC-3 human prostate cancer cells and mice prostate cancer model	Cell migration, invasion, growth inhibition, and apoptosis assays	Oral gavage	0, 25, and 50 μM for 48 h. 150 and 300 mg/kg BW for 8 weeks	(1) Inhibited the migration and invasion of PC-3 cells in vitro; (2) Decreased the growth of PC-3 tumors and lymph node and lung metastases in a dose-dependent manner in mice; (3) Exhibited anticancer activity via induction of apoptosis, reduction of prostate tumor angiogenesis, and reduction of CXCR4 expression	Feng et al. (2012)
Ampelopsin-sodium (purity not provided)	BALB/c mice	Mice implanted with human bladder carcinoma EJ cells and murine sarcoma 180 cells	IP/IV/II administration	160, 200, and 260 mg/kg BW for 2-3 weeks	DHM considerably inhibited the proliferation of EJ and sarcoma 180 cells both in vivo and in vitro	Baolai et al. (2012)
	Human glioma cell lines U251 and A172, and male BALB/c-nu mice xenograft model	Apoptosis and tumor growth inhibition	Intraperitoneal administration	25, 50, 100 μM for 24 h and 50 and 100 mg/kg BW for 30 days	(1) Induced apoptosis by arresting at G1 and S phases and autophagy through potentiating ROS generation and JNK activation in human glioma cells; (2) DHM activated caspase 8, caspase 9, and caspase 3 contributing to PARP cleavage; (3) Reduced tumor growth of human glioma xenograft in mice	Zhigang et al. (2019)
DHM 98%	Colo-205 cells and xenograft tumor transplant mice	Cell growth inhibition assays	Intragastric administration	25, 50, and 100 mg/kg BW for 21 days	Inhibited the proliferation and growth of Colo-205 colon cancer cells considerably in vivo and in vitro via suppression of the expression and secretion of Sema4D	Jun et al. (2019)