Review Article

Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge

Table 1

Lipophilic components from Salvia miltiorrhiza that modify ROS-related effects on cancer cells.

Components [reference]Cancer cellsEffects

Tanshinones [16]Lung cancer 95D cellsInduces apoptosis and prosurvival autophagy mediated by increasing the formation of intracellular ROS

Tanshinone I [17]Prostate cancer cellsEnhances TRAIL via upregulation of miR-135a-3p-mediated death receptor 5

Tanshinone I [18]Human breast cancer MDA-MB-453 cellsInduces antiproliferative activity and cell cycle arrest by inhibiting the PI3K/Akt/mTOR signaling pathways

Tanshinone I [19]Leukemia U937 THP-1 and SHI 1 cellsInduces apoptosis by activating caspase-3 and decreasing hTERT mRNA expression and telomerase activity, as well as downregulating survivin expression

Tanshinone IIA [20]Prostate cancer cellsInduces apoptosis and autophagy that depends on intracellular ROS production

Tanshinone IIA [21]Gastric cancer cellsSuppresses cell growth by blocking glucose metabolism

Tanshinone IIA [22]Human non-small cell lung cancer A549 cellsDecreases VEGF/VEGFR2 expression and induces apoptosis and cell cycle arrest at the S phase

Tanshinone IIA [23]Human oral cancer KB cellsInduces apoptosis through the mitochondria-dependent pathway in which there is a loss of the mitochondrial membrane potential and activation of caspase-3 and caspase-9

Tanshinone IIA [24]Human colon cancer cellsUDP-glucuronosyltransferase 1A compromises the intracellular accumulation and resultant apoptotic effect of tanshinone IIA

Tanshinone IIA [25]Cervical cancer CaSki cellsInhibits cell growth by activating ER stress pathways and promoting caspase cascades with concomitant upregulation of p38 and JNK phosphorylation and signaling

Tanshinone IIA [26]Human hepatoma J5 cellsIncreases Bax and caspase-3 and decreases CD31 expression

Tanshinone IIA [27]Non-small cell lung cancer H596 cellsActivates ROS-triggered, p53-independent, and caspase-dependent mitochondrial apoptotic cell death pathway

Tanshinone IIA [28]786-O human renal cell carcinoma cellsInduces apoptosis by activating p53 expression and subsequently upregulating p21 and Bax

Tanshinone IIA [29]Leukemia U937 cellsInduces apoptosis by activating PXR, which suppresses the activity of NF-κB

Tanshinone IIA [30]human non-small lung cancer A549 cellsInduces apoptosis by increasing ROS and the ratio of Bax/Bcl-2 and then decreasing the mitochondrial membrane potential, which leads to cytochrome c release

Tanshinone IIA [31]Small cell lung cancer H146 cellsInhibits cell growth by upregulating the Bax/Bcl-2 ratio and decreasing the mitochondrial membrane potential

Tanshinone IIA [32]Cervical cancer HeLa cellsInhibits cell growth by interfering with the process of microtubule assembly, leading to G2/M phase arrest and subsequent apoptosis

Acetyltanshinone IIA [33]Breast cancerInduces G1/S phase arrest and apoptosis by downregulating the receptor tyrosine kinases EGFR/HER2 and activating AMP-activated protein kinase

Acetyltanshinone IIA [34]Breast cancer cellsInduces ROS generation and Bax translocation to mitochondria, resulting in mitochondrial damage, cytochrome c release, caspase-3 activation, and apoptotic cell death

Cryptotanshinone [35]Breast cancer cellsSuppresses estrogen receptor signaling

Cryptotanshinone [36]Acute lymphoblastic leukemia cellsInhibits cellular movement and induces G2/M cell cycle arrest and apoptosis

Cryptotanshinone [37]Lung cancer cellsInduces prodeath autophagy through JNK signaling that is mediated by ROS generation

Cryptotanshinone [38]HepG2 hepatomaInduces G1 cell cycle arrest and autophagic cell death by activating the AMP-activated protein kinase signaling pathway

Cryptotanshinone [39]A375 melanoma cellsRestores sensitivity in cancer cells that are resistant to TRAIL by upregulating DR5 expression

Cryptotanshinone [40]Rh30 human rhabdomyosarcoma; DU145 prostate carcinoma; and human MCF-7 breast cancer cellsInduces ROS, thereby activating p38/JNK and inhibiting Erk1/2 leading to caspase-independent cell death

Cryptotanshinone [41]Neuro-2a cellsInhibits sodium nitroprusside-induced apoptosis by antioxidant effects and regulating the NF-κB and MAPK pathways

Cryptotanshinone [42]HepG2 hepatoma and MCF-7 breast cancer cellsInduces ER stress-mediated apoptosis

Cryptotanshinone [43]Prostate cancer cellsSuppresses androgen receptor- (AR-) mediated growth by blocking AR dimerization and formation of the AR-coregulator complex

Cryptotanshinone [44]Chronic myeloid leukemia KBM-5 cellsEnhances TNF-α-induced apoptosis through ROS-dependent activation of caspase-8 and p38

Isocryptotanshinone [45]Human breast cancer MCF-7 cellsInduces apoptosis and activates MAPK signaling pathways

Dihydrotanshinone [46]HepG2 cellsActivates ROS-mediated phosphorylation of p38 MAPK

Dihydrotanshinone I [47]Colon cancerInduces caspase- and ROS-dependent apoptosis and autophagy

15,16-Dihydrotanshinone I [48]Human HL-60 Leukemia CellsInduces apoptosis through activation of the JNK and FasL signaling pathways

Miltirone [49]Human hepatoma HepG2 cellsActivates caspase-dependent apoptotic pathways and triggers ROS-mediated MAPK signaling pathways

Miltirone [50]Acute lymphoblastic leukemia cellsInduces G2/M cell cycle arrest and apoptosis