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. 2020 Jul 8;11:1009. doi: 10.3389/fphar.2020.01009

Table 5.

Effect of TCM on cell death of tumor cells.

TCM Tumor type Effects Main mechanisms Ref.
Induction of apoptosis
AST
(TCM component)
In vitro, HT-29 CRC cells Could induce the extrinsic apoptotic cascade and caused cell cycle arrest Regulating both mTOR and ERK signaling pathways, inhibition of NF-kappaB is a critical latter event (Auyeung et al., 2010)
LJGP
(TCM component)
In vitro, AGS gastric cancer cells Could inhibit tumor growth and induce apoptosis by upregulating pro-apoptotic Bax, and downregulating anti-apoptotic Bcl-2 and IAP family members, as well as activation of caspase-3/9 downregulating telomerase activity and prostaglandin E2 synthesis by decreasing COX-2 (Ho et al., 2011)
PHY906
formula
In vivo, a nude mouse xenograft model of HepG2 Could increase cell apoptosis Increasing mouse FasL and human FasR expression (Lam et al., 2015)
YWKLF
formula
In vitro, human gastric cancer MGC-803 cells The sera from rabbits orally administered with YWKLF induced cell apoptosis Inducing mitochondrial dysfunction, increasing the expression of Fas and Bax, and reducing the mRNA levels of FasL (Li et al., 2008)
Induction of autophagy
Bufalin
(TCM monomer)
In vitro, human hepatoma cancer Huh7, Hep3B and HA22T cells Could inhibit the proliferation, regulate the cell death program, and induce autophagy Increasing TNF, MAPK and BECN-1 and ATG8, and decreasing Bcl-2 and Bid (Hsu et al., 2013)
DHA-37
(TCM monomer)
In vitro and in vivo, multiple human cancer cell lines including A549 SGC-7901, and a murine xenograft model of A549 Could trigger ACD in A549 cells and inhibit tumor growth in vivo Activating the MAPK signal and upregulating HMGB1 in vitro and increasing p-ERK, p-P38, HMGB1, and LC3 in tumor tissue (Liu et al., 2018)
PGB
(TCM component)
In vitro, human lung carcinoma A549 cells Could induce ACD of A549 cells Suppressing the AKT/mTOR pathway, and activating the AMPK and MAPK pathways (Ma et al., 2016)
FOJ and SSOJ
(Components of OJ formula)
In vitro, human lung carcinoma A549 cells Could induce autophagy of A549 cells by upregulating protein levels of LC3-II and mRNA levels of Atg-3, Atg-7, Beclin-1 and LC3-II/I Inhibiting the PI3K/Akt/mTOR signaling (Chen J. et al., 2017)
Induction of necroptosis
Resibufogenin (TCM monomer) In vivo, a murine xenograft model of CRC Could suppress tumor growth and metastasis Induction of necroptosis through increasing RIP3 and pMLKL (Han et al., 2018)
Shikonin
(TCM monomer)
In vitro, rat C6 and human U87 glioma cells Could induce necroptosis Mediated by oxidative stress and RIP1 signaling (Huang C. et al., 2013)
Induction of multiple cell death pathways
SB
(TCM component)
In vitro and in vivo, human lung cancer CL1-5 cells and a murine xenograft model of lung cancer Could suppress proliferation and angiogenesis, and increase apoptosis and autophagy ER stress-, intrinsic mitochondrial-, P38/SIRT1-regulated cell apoptosis through G2/M phase arrest and extrinsic Fas/FasL-mediated pathways (Chen C.C. et al., 2017)
HLP
(TCM component)
In vitro, human malignant melanoma A375 cells Could induce apoptosis and ACD in A375 cells Increasing the caspases cleavages, Bcl-2, and Fas/FasL activation and ATG5, Beclin1, and LC3-II (Chiu et al., 2015)
Shikonin
(TCM monomer)
In vitro and in vivo, mouse stage IV mammary carcinoma 4T1-luc2 cells and a murine model of mammary carcinoma Could trigger RIP1- and RIP3-dependent necroptosis and autophagy, and stimulate the derived vaccine efficacy Enhancing the surface DMAP activity and DC activation (Lin et al., 2018)

AST, The total saponins of Astragalus mongholicus Bunge [Fabaceae]; CRC, colorectal cancer; LJGP, Glycoprotein isolated from Laminaria japonica; YWKLF, a herbal medicine formula Yang Wei Kang Liu; DHA-37, Dihydroartemisinin; ACD, autophagic cell death; HMGB1, high mobility group protein; PGB, the platycoside-containing butanol fraction of PG; FOJ, Flavonoids; SSOJ, steroidal saponins; OJ, Ophiopogon japonicus (Thunb.) Ker Gawl. [Asparagaceae]; SB, Scutellaria barbata D.Don [Lamiaceae]; HLP, Hibiscus leaf polyphenolic.