TABLE 1.
Phytochemicals that activate autophagy and apoptosis in various in vitro and in vivo cancer models.
| Phytochemicals | Doses/Conc | Cancer model | Molecular effects | References |
|---|---|---|---|---|
| Resveratrol | 10–100 μM | Human colon carcinoma cell lines SW480, SW620, B103, and HCT116 | Activate procaspase-3, 8/FADD | Delmas et al. (2003); Rahman et al. (2012a) |
| Eriocalyxin B (EriB) | 1.4 μM | Human pancreatic cancer cellPANC-1, SW1990 CAPAN-2, and CAPAN-1 | Caspase 8,9 activation and downstream regulation of caspases 3, 7, PARP | Li et al. (2012) |
| β-Elemene | 10 μM | Human breast cancer cell lines Bcap37, MBA-MD-231 | Conservation of LC3-I to LC3-II | Guan et al. (2014) |
| Oblongifolin C | 15 μM | Human breast carcinoma cell lines HeLa or MEF | Activation of CASP3 and cleaved PARP | Lao et al. (2014) |
| Apigenin | 10 μM | Colorectal cancer cells HCT-116, SW480, HT-29 and LoVo | Activate NAG-1, p53, p21 | Zhong et al. (2010) |
| Allicin | 1 μg/ml | Human gastric cancer cell line MGC-803, BGC-823 and SGC-7901 | Increase expression of p38 and cleaved Of caspase 3 | Zhang et al. (2015) |
| Anthocyanins | 50 µM | Breast cancer cell lines MCF-MDA-MB-231 and MDA-MB-453 | Inhibit the expression of VEGF, suppressed the MMP-9,MMP-2 and uPA expression | Hui et al. (2010) |
| Aspalathin | 0.2 µM | Ovarian cancer cell Caov-3 | Inhibit Dox, decrease expression of p53 and induce AMPK and Foxo1 | Lin et al. (2017) |
| Baicalein | 200 µM | Human HCC cell lines SMMC-772 and Bel-7402 | Downregulate Bcl 2, increase ER stress | Wang et al. (2014) |
| Berberine | 100 nM | Human glioma cell lines U251 and U87 GBM | Inhibition of AMPK/mTOR/ULK1 | Peng et al. (2008); Wang et al. (2010); Yu et al. (2014); Guamán Ortiz et al. (2015); Wang et al. (2016a) |
| Capsaicin | 150 µM | Human nasopharyngeal carcinoma cell line NPC-TW01 | Downstream of PI3K/Akt/mTOR, increase caspase-3 activity | Lin et al. (2017b) |
| Celastrol | 1.5 μM | Human prostate cancer cell lines LNCaP, 22Rv1, DU145 and PC-3 | Upstream of miR-101 | Guo et al. (2015) |
| Cordycepin | 200 µM | Human brain cancer cellSH-SY5Y and U-251 | Upregulates ROS, p53, and LC3II | Chaicharoenaudomrung et al. (2018) |
| Curcumin | 25 µM | Malignant mesotheloma cancer cell line MM-B1, H-Meso-1, and MM-F1 | Increase Bax/bcl-2 ratio, p53 expression, activation of caspase 9, cleavage of PARP-1 | Masuelli et al. (2017) |
| Epigallocatechin gallate (EGCG) | 100 nM | Vascular endothelial cell line U-937 | Reduce TNF-α, inhibit VCAM1, LC3A, LC3B | Yamagata et al. (2015) |
| Evodiamine | 10 µM | Gastric cancer cell line SGC-7901 | Activates beclin-2, Bax, downregulates Bcl-2 | Rasul et al. (2012) |
| Fisetin | 40–120 µM | Prostate cancer cell lines PC3 and DU145 | Supressed Mtor and inhibit Akt, activate AMPK | Suh et al. (2010) |
| Genistein | 50–100 µM | Ovarian cancer cell line A2780 | Reduces Akt/mTOR phosphorylation | Gossner et al. (2007) |
| Gingerol | 300 µM | Human colon cancer cell lines SW-480 and HCT116 | Inhibition of JNK, ERK1-2, and P38 MAPK | Shukla and Singh, (2007); Baliga et al. (2011); Radhakrishnan et al. (2014) |
| Ginsenoside F2 | 100 µM | Breast cancer cell lines MCF-7 | Elevated Atg-7 | Mai et al. (2012) |
| Cleaved PARP | ||||
| Hispolon | 25–100 µM | Cervical cancer cell lines Hela and SiHa | Downregulated lysosomal protease Cathepsin S(CTSS) | Chen et al. (2012) |
| 3′-hydroxydaidzein (3′-ODI) | 100 µM | Mouse melanoma cell line B16F1 | Reduce the α-MSH | Kim et al. (2013) |
| Toxicarioside O | 50 nM | Human colorectal cancer cell lines HCT116 and SW480 | Inhibition of the Akt/mTOR | Huang et al. (2017) |
| Upstream SIRT1↑ | ||||
| Falcarindiol | 6 µM | Human breast cancer cell lines MDA-MB-231,MDA-MB-468 and Her2 | FAD induce expression of GRP78 | Minto and Blacklock, (2008); Jin et al. (2012); Lu et al. (2017) |
| Oleanolic acid | 100 μg/ml | Human pancreatic cancer cell line Panc‐28 | Modulate JNK and mTOR pathway | Pollier and Goossens, (2012); Liu et al. (2014) |
| Honokiol | 40 μM | Human glioblastoma cell lines LN229, GBM8401 and U373 | Reduction of p-PI3K, p-Akt and Ki67 | Cheng et al. (2016) |
| Magnolol | 40 μM | Human glioblastoma cell lines LN229, GBM8401 and U373 | Reduction of p-PI3K, p-Akt and Ki67 | Cheng et al. (2016) |
| Alisol B | 30 μM | Breast cancer cell lines MCF-7, SK-BR-3, and HeLa | Activation of Ca2+/AMPK/Mtor | Law et al. (2010) |
| Luteolin | 100 µM | Human liver cancer SMMC-7721 | Increase expression of caspase-8, decrease bcl-2 | Cao et al. (2017) |
| α-Mangostin | 5–10 µM | Human brain cancer cell lines, GBM8401 and DBTRG05MG | Activation of AMPK | Chao et al. (2011) |
| Oridonin | 8–32 μmol/L | Human hepatocellular carcinoma cell line BEL-7402 | Activation of caspase-3 | Zhang et al. (2006) |
| Down-regulation of Bcl-2 and Up-regulation of Bax | ||||
| Quercetin | 15 µM | Lymphoma cell lines BC3, BCBL1 and BC1 | Inhibits PI3K/Akt/mTOR and Wnt/β-catenin | Granato et al. (2017) |
| Rottlerin | 1–2 µM | Breast cancer cell lines CD44/CD24 | Enhance expression of LC3 | Kumar et al. (2013) |
| 6-Shogaol | 55.4 μM | Lung cancer cell line A549 | Inhibition af Akt and mTOR downstream | Hung et al. (2009) |
| Silibinin (silybin) | 50 µM | RCC cell lines ACHN and 786-O | Inhibit mTOR and activate AMPK | Li et al. (2015) |
| Sulforaphane | 40 µM | Human pancreatic cancer cell lines MIA PaCa-2,Panc-1 | Increase ROS level | Naumann et al. (2011) |
| γ-tocotrienol | 10 μmol/L | Breast cancer cell lines MCF-7 and MDA-MB-231 | Activate AMPK, down regulate Ang-1/Tie-2 | Ling et al. (2012); Tang et al. (2019) |
| Thymoquinone | 40–60 µM | Oral cancer cell lines SASVO3,SCC-4, OCT,SAS | Increase expression of LC3-II, Bax expression | Chu et al. (2014) |
| Tripchlorolide | 200 nM | Lung cancer cell line A549/DDP | Inhibition of PI3K/Akt/mTOR | Chen et al. (2017a) |
| Tetrandrine | 0–4 μM | Hepatocellular carcinoma cell lines Huh7, HCCLM9 and Hep3B | Inhibits Wnt/β-catenin | Zhang et al. (2018) |
| Decreases MTA1 | ||||
| N-desmethyldauricine | 150 μM | Lung cancer cell line H1299 | Inhibition of Ulk-1/PERK/AMPK/mTOR | Law et al. (2017) |
| Quinacrine | 15 μM | Colon cancer cell lines HCT-116/HCT-116/HCT-116 | Activation of p53, p21, and inhibition of topoisomerase | Mohapatra et al. (2012) |
| Chloroquine | 50 μM | Pancreatic cancer cell line MiaPaCa2 and S2VP10 | Decrease the level of O2 | Frieboes et al. (2014) |
| Tangeritin | 10 μM | Breast cancer cell lines MCF7, MDA–MB–468 and MCF10A | Induce CYP1 and CYP1A1/CYP1B1 protein expression | Surichan et al. (2018) |
| Myricetin | 100 μM/L | Prostate cancer cell lines PC3, DU145 | Knockdown the interaction between P1M1/CXCR4 | Ye et al. (2018) |
| Galangin | 15 μM | Human kidney cancer cell line A498 | Inhibition of PI3K/Akt/mTOR signaling | Zhu et al. (2018) |
| Isorhamnetin | 100 μM | Colon cancer cell lines HCT116 and SW480 | Increase ROS | Wu et al. (2018) |
| Hesperetin | 350 μM | Lung cancer cell line H522 | Knockdown caspase-3/9,p53,Bax | Elango et al. (2018) |
| Upregulate Fas, FADD and caspase-8 | ||||
| Delphinidin | 80 μM | Breast cancer cell lines MDA-MB-453 and BT474 | Suppression of mTOR | Chen et al. (2018) |
| Activation of the AMPK | ||||
| Epigallocatechingallate (EGCG) | 500 μM | Human glioblastoma cell lines T98G and U87MG | Increase ROS | Grube et al. (2018) |
| Epicatechin-3-O-gallate (ECG) | 36 µM | Prostate cancer cell lines LNCaP and PC-3 | Diminished the progression of carcinofenic cell | Siddiqui et al. (2011); Stadlbauer et al. (2018) |
| Cyanidin‐3‐glucoside (C3G) | 20 μM | Human breast cancer MDA‐MB‐231 and Hs‐578T | Inhibiting STAT3/VEGF and miR124 mediated downregulation STAT3 | Ma and Ning, (2019) |
| Benzyl isothiocyanate (BITC) | 6.5 μM | Pancreatic cell lines BxPC-3 and PanC-1 | Decrease the phosphorylation of PI3K/Akt/FOXO1/PDK1/mTOR/FOXO3a | Boreddy et al. (2011) |
| Phenethyl isothiocyanates (PEITC) | 10 μM | Breast cancer cell lines MDA-MB-231 and MCF-7 | Reduction of HER2, EGFR and STAT3 expression | Gupta and Srivastava, (2012) |
| Piperlongumine (PL) | 6 µM | Lung cancer cell lines A549 and A549/DTX | Regulate PI3K/Akt/mTOR | Bezerra et al. (2008); Raj et al. (2011); Wang et al. (2015) |
| Saikosaponin-d | 10 µM | Breast cancer cell lines HeLa and MCF-7 | Calcium mobilization, induce CaMKKβ-AMPK-mTOR | Hsu et al. (2004); Tundis et al. (2009); Wong et al. (2013) |
| Guttiferone K | 20 µM | Human HCCs HuH7 and HepG2 | Reduce phosphorylation of Akt/mTOR, increase ROS | Xu et al. (2008) |
| Wu et al. (2015) | ||||
| Licochalcone A | 20 or 50 µM | Breast cancer cell line MCF-7 | Suppression of PI3K/Akt/mTOR pathway | Xue et al. (2018) |
| Ophiopogonin B | 10 μM | Lung cancer (NSCLC) cell lines NCI-H157 and NCI-H460 | Inhibition of PI3K, Akt, mTOR | Chen et al. (2013a) |
| Norcantharidin | 40 μM | Human MHCC-97H (97H) and HepG2 HCC cells | Inhibition of c-Met, mTOR | Sun et al. (2017a) |
| Juglanin | 10 μM | Breast cancer cell lines MCF-7 and SKBR3 | Regulation of ROS, JNK | Sun et al. (2017b) |
| Isoliquiritigenin | 25 μM | Human ovarian cancer cell lines, OVCAR5 and ES-2 | Cleaved caspase-3, increased LC3B-II, and Beclin-1 level | Chen et al. (2017b) |
| Cucurbitacin B | 200 μM | Breast cancer cell line MCF-7 | Increase γH2AX, phosphorylation of ATM/ATR, ROS | Chen et al. (2005); Ren et al. (2015) |
| Carnosol | 25 µM | Human breast cancer cell line MDA-MB-231 | Increase p21/WAF1 and downregulate p27 | Al Dhaheri et al. (2014) |
| Kaempferol | 50 or 100 μM | Colorectal cancer cell lines HCT116, HCT15, and SW480 | Generated ROS and p53 signal | Choi et al. (2018) |
| Ursolic acid | 10–40 µM | Prostate cancer cell lines PC3 | Increases Beclin-1/Atg5 and inhibits Akt/mTOR | Shin et al. (2012) |
| Triptolide | 200 nM | Human pancreatic cancer cell line S2-013, S2-VP10, and Hs766T | Inhibits of Akt-mTOR-P70S6K | Mujumdar et al. (2010) |