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Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 1, pp 17–26 | Cite as

Autophagy and its potent modulators from phytochemicals in cancer treatment

  • Chao-Yue Sun
  • Qian-Yu Zhang
  • Guang-Juan ZhengEmail author
  • Bing FengEmail author
Review Article
First Online:

Abstract

Autophagy is a ubiquitous catabolic process by which damaged or harmful intracellular components are delivered to the lysosomes for self-digestion and recycling. It is critical in cancer treatment. Therapy-induced autophagy predominantly acts as a pro-survival mechanism, but progressive autophagy can lead to non-apoptotic cell death, also known as autophagic cell death. Plants or herbs contain various natural compounds that are widely used in the treatment of many types of malignancies. Emerging evidence indicates that phytochemicals targeting the autophagic pathway are promising agents for cancer treatment. However, these compounds play different roles in autophagy. In this review, we discussed the role of autophagy in cancer development and therapy, and focussed on elucidating the anti-cancer activities of autophagic modulators, especially phytochemicals. Notably, we described a novel premise that the dynamic role of phytochemicals should be evaluated in regulation of autophagy in cancer.

Keywords

Autophagy Modulators Phytochemicals Cancer Degree 
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Notes

Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (Grant no. 81403142), and the Science and Technology Planning Project of Guangdong Province (Grant no. 2016A020226048).

Compliance with ethical standards

Conflict of interest

All four authors declare that they have no conflicts of interest.

Ethical approval

This review does not contain any experiments involving humans or animals, and hence ethical clearance was not required.

References

  1. 1.
    Krishnamurthy S, Konstantinou EK, Young LH, Gold DA, Saeij JP (2017) The human immune response to toxoplasma: autophagy versus cell death. PLoS Pathog 13:e1006176Google Scholar
  2. 2.
    Lin XT, Zheng XB, Fan DJ, Yao QQ, Hu JC, Lian L et al (2018) MicroRNA-143 targets ATG2B to inhibit autophagy and increase inflammatory responses in Crohn’s disease. Inflamm Bowel Dis 24:781–791Google Scholar
  3. 3.
    Kato H, Perl A (2018) Blockade of Treg cell differentiation and function by the interleukin-21-mechanistic target of rapamycin axis via suppression of autophagy in patients with systemic lupus erythematosus. Arthritis Rheumatol 70:427–438Google Scholar
  4. 4.
    Meng Y, Pan M-x, Zheng B-j, Chen Y, Li W, Yang Q-j et al (2018) Autophagy attenuates angiotensin II-induced pulmonary fibrosis by inhibiting redox imbalance-mediated NLRP3 inflammasome activation. Antioxid Redox Signal.  https://doi.org/10.1089/ars.2017.7261 Google Scholar
  5. 5.
    Ryter SW, Bhatia D, Choi ME (2018) Autophagy: a lysosome-dependent process with implications in cellular redox homeostasis and human disease. Antioxid Redox Signal.  https://doi.org/10.1089/ars.2018.7518 Google Scholar
  6. 6.
    Yang D, Livingston MJ, Liu Z, Dong G, Zhang M, Chen JK et al (2018) Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential. Cell Mol Life Sci CMLS 75:669–688Google Scholar
  7. 7.
    Qian Q, Zhang Z, Orwig A, Chen S, Ding WX, Xu Y et al (2018) S-Nitrosoglutathione reductase dysfunction contributes to obesity-associated hepatic insulin resistance via regulating autophagy. Diabetes 67:193–207Google Scholar
  8. 8.
    Uddin MS, Stachowiak A, Mamun AA, Tzvetkov NT, Takeda S, Atanasov AG et al (2018) Autophagy and Alzheimer’s disease: from molecular mechanisms to therapeutic implications. Front Aging Neurosci 10:04Google Scholar
  9. 9.
    Deng Z, Sheehan P, Chen S, Yue Z (2017) Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease? Mol Neurodegener 12:90Google Scholar
  10. 10.
    Zhang J, Culp ML, Craver JG, Darley-Usmar V (2018) Mitochondrial function and autophagy: integrating proteotoxic, redox, and metabolic stress in Parkinson’s disease. J Neurochem 144:691–709Google Scholar
  11. 11.
    White E (2015) The role for autophagy in cancer. J Clin Investig 125:42–46Google Scholar
  12. 12.
    Zhao P, Li M, Wang Y, Chen Y, He C, Zhang X et al (2018) Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles. Acta Biomater 72:248–255Google Scholar
  13. 13.
    Rebecca VW, Amaravadi RK (2016) Emerging strategies to effectively target autophagy in cancer. Oncogene 35:1–11Google Scholar
  14. 14.
    Sun Y, Huang YH, Huang FY, Mei WL, Liu Q, Wang CC et al (2018) 3′-epi-12beta-hydroxyfroside, a new cardenolide, induces cytoprotective autophagy via blocking the Hsp90/Akt/mTOR axis in lung cancer cells. Theranostics 8:2044–2060Google Scholar
  15. 15.
    Sun CY, Zhu Y, Li XF, Wang XQ, Tang LP, Su ZQ et al (2018) Scutellarin increases cisplatin-induced apoptosis and autophagy to overcome cisplatin resistance in non-small cell lung cancer via ERK/p53 and c-met/AKT signaling pathways. Front Pharmacol 9:92Google Scholar
  16. 16.
    Sun CY, Zhu Y, Li XF, Tang LP, Su ZQ, Wang XQ et al (2017) Norcantharidin alone or in combination with crizotinib induces autophagic cell death in hepatocellular carcinoma by repressing c-Met-mTOR signaling. Oncotarget 8:114945–114955Google Scholar
  17. 17.
    Onorati AV, Dyczynski M, Ojha R, Amaravadi RK (2018) Targeting autophagy in cancer. Cancer 124(16):3307–3318Google Scholar
  18. 18.
    Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K et al (2007) Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev 21:1367–1381Google Scholar
  19. 19.
    Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S et al (2007) Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 21:1621–1635Google Scholar
  20. 20.
    White E, Mehnert JM, Chan CS (2015) Autophagy, metabolism, and cancer. Clin Cancer Res Off J Am Assoc Cancer Res 21:5037–5046Google Scholar
  21. 21.
    Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S et al (2011) Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25:795–800Google Scholar
  22. 22.
    Rosenfeldt MT, O’Prey J, Morton JP, Nixon C, MacKay G, Mrowinska A et al (2013) p53 status determines the role of autophagy in pancreatic tumour development. Nature 504:296–300Google Scholar
  23. 23.
    Vega-Rubin-de-Celis S, Zou Z, Fernandez AF, Ci B, Kim M, Xiao G et al (2018) Increased autophagy blocks HER2-mediated breast tumorigenesis. Proc Natl Acad Sci USA 115:4176–4181Google Scholar
  24. 24.
    Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G et al (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes development 25:460–470Google Scholar
  25. 25.
    Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H et al (2011) Pancreatic cancers require autophagy for tumor growth. Genes Dev 25:717–729Google Scholar
  26. 26.
    Yang A, Herter-Sprie G, Zhang H, Lin EY, Biancur D, Wang X et al (2018) Autophagy sustains pancreatic cancer growth through both cell-autonomous and nonautonomous mechanisms. Cancer Discov 8:276–287Google Scholar
  27. 27.
    Piya S, Andreeff M, Borthakur G (2016) Targeting autophagy to overcome chemoresistance in acute myleogenous leukemia. Autophagy 13:214–215Google Scholar
  28. 28.
    Das CK, Mandal M, Kogel D (2018) Pro-survival autophagy and cancer cell resistance to therapy. Cancer Metastasis Rev 13:1–8Google Scholar
  29. 29.
    Sui X, Chen R, Wang Z, Huang Z, Kong N, Zhang M et al (2013) Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis 4:e838Google Scholar
  30. 30.
    Zeng J, Liu W, Fan YZ, He DL, Li L (2018) PrLZ increases prostate cancer docetaxel resistance by inhibiting LKB1/AMPK-mediated autophagy. Theranostics 8:109–123Google Scholar
  31. 31.
    Gong C, Hu C, Gu F, Xia Q, Yao C, Zhang L et al (2017) Co-delivery of autophagy inhibitor ATG7 siRNA and docetaxel for breast cancer treatment. J Controll Release Off J Controll Release Soc 266:272–286Google Scholar
  32. 32.
    Hu F, Zhao Y, Yu Y, Fang JM, Cui R, Liu ZQ et al (2018) Docetaxel-mediated autophagy promotes chemoresistance in castration-resistant prostate cancer cells by inhibiting STAT3. Cancer Lett 416:24–30Google Scholar
  33. 33.
    Tan Q, Joshua AM, Saggar JK, Yu M, Wang M, Kanga N et al (2015) Effect of pantoprazole to enhance activity of docetaxel against human tumour xenografts by inhibiting autophagy. Br J Cancer 112:832–840Google Scholar
  34. 34.
    Yuan X, Du J, Hua S, Zhang H, Gu C, Wang J et al (2015) Suppression of autophagy augments the radiosensitizing effects of STAT3 inhibition on human glioma cells. Exp Cell Res 330:267–276Google Scholar
  35. 35.
    Cerniglia GJ, Karar J, Tyagi S, Christofidou-Solomidou M, Rengan R, Koumenis C et al (2012) Inhibition of autophagy as a strategy to augment radiosensitization by the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Mol Pharmacol 82:1230–1240Google Scholar
  36. 36.
    Zhou Z, Yan Y, Hu K, Zou Y, Li Y, Ma R et al (2017) Autophagy inhibition enabled efficient photothermal therapy at a mild temperature. Biomaterials 141:116–124Google Scholar
  37. 37.
    Domagala A, Stachura J, Gabrysiak M, Muchowicz A, Zagozdzon R, Golab J et al (2018) Inhibition of autophagy sensitizes cancer cells to photofrin-based photodynamic therapy. BMC Cancer 18:210Google Scholar
  38. 38.
    Mulcahy Levy JM, Zahedi S, Griesinger AM, Morin A, Davies KD, Aisner DL et al (2017) Autophagy inhibition overcomes multiple mechanisms of resistance to BRAF inhibition in brain tumors Elife 6:e19671Google Scholar
  39. 39.
    Xiong HY, Guo XL, Bu XX, Zhang SS, Ma NN, Song JR et al (2010) Autophagic cell death induced by 5-FU in Bax or PUMA deficient human colon cancer cell. Cancer Lett 288:68–74Google Scholar
  40. 40.
    Mujumdar N, Mackenzie TN, Dudeja V, Chugh R, Antonoff MB, Borja-Cacho D et al (2010) Triptolide induces cell death in pancreatic cancer cells by apoptotic and autophagic pathways. Gastroenterology 139:598–608Google Scholar
  41. 41.
    Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on cell death 2018. Cell Death Differ 25:486–541Google Scholar
  42. 42.
    Fulda S, Kogel D (2015) Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy. Oncogene 34:5105–5113Google Scholar
  43. 43.
    Kuo PL, Hsu YL, Cho CY (2006) Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther 5:3209–3221Google Scholar
  44. 44.
    Wong VK, Li T, Law BY, Ma ED, Yip NC, Michelangeli F et al (2013) Saikosaponin-d, a novel SERCA inhibitor, induces autophagic cell death in apoptosis-defective cells. Cell Death Dis 4:e720Google Scholar
  45. 45.
    Wang N, Feng Y, Zhu M, Tsang CM, Man K, Tong Y et al (2010) Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism. J Cell Biochem 111:1426–1436Google Scholar
  46. 46.
    Al Dhaheri Y, Attoub S, Ramadan G, Arafat K, Bajbouj K, Karuvantevida N et al (2014) Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer. PloS One 9:e109630Google Scholar
  47. 47.
    Miao Q, Bi LL, Li X, Miao S, Zhang J, Zhang S et al (2013) Anticancer effects of bufalin on human hepatocellular carcinoma HepG2 cells: roles of apoptosis and autophagy. Int J Mol Sci 14:1370–1382Google Scholar
  48. 48.
    Maheswari U, Ghosh K, Sadras SR (2018) Licarin A induces cell death by activation of autophagy and apoptosis in non-small cell lung cancer cells. Apoptosis Int J Program Cell Death 23:210–225Google Scholar
  49. 49.
    Chen HY, Huang TC, Shieh TM, Wu CH, Lin LC, Hsia SM (2017) Isoliquiritigenin induces autophagy and inhibits ovarian cancer cell growth. Int J Mol Sci 18:2025Google Scholar
  50. 50.
    Zhao F, Huang W, Zhang Z, Mao L, Han Y, Yan J et al (2016) Triptolide induces protective autophagy through activation of the CaMKKβ-AMPK signaling pathway in prostate cancer cells. Oncotarget 7:5366–5382Google Scholar
  51. 51.
    Zhou X, Yue GG, Chan AM, Tsui SK, Fung KP, Sun H et al (2017) Eriocalyxin B, a novel autophagy inducer, exerts anti-tumor activity through the suppression of Akt/mTOR/p70S6K signaling pathway in breast cancer. Biochem Pharmacol 142:58–70Google Scholar
  52. 52.
    Zhao S, Ma CM, Liu CX, Wei W, Sun Y, Yan H et al (2012) Autophagy inhibition enhances isobavachalcone-induced cell death in multiple myeloma cells. Int J Mol Med 30:939–944Google Scholar
  53. 53.
    Xie CY, Yang W, Li M, Ying J, Tao SJ, Li K et al (2009) Cell apoptosis induced by delta-elemene in colorectal adenocarcinoma cells via a mitochondrial-mediated pathway. Yakugaku Zasshi 129:1403–1413Google Scholar
  54. 54.
    Liu J, Hu XJ, Jin B, Qu XJ, Hou KZ, Liu YP (2012) β-Elemene induces apoptosis as well as protective autophagy in human non-small-cell lung cancer A549 cells. J Pharm Pharmacol 64:146–153Google Scholar
  55. 55.
    Liu J, Zhang Y, Qu J, Xu L, Hou K, Zhang J et al (2011) β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis. BMC Cancer 11:183Google Scholar
  56. 56.
    Mai TT, Moon J, Song Y, Viet PQ, Phuc PV, Lee JM et al (2012) Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells. Cancer Lett 321:144–153Google Scholar
  57. 57.
    Huang YH, Sun Y, Huang FY, Li YN, Wang CC, Mei WL et al (2017) Toxicarioside O induces protective autophagy in a sirtuin-1-dependent manner in colorectal cancer cells. Oncotarget 8:52783–52791Google Scholar
  58. 58.
    Li X, Li X, Wang J, Ye Z, Li JC (2012) Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells. Int J Biol Sci 8:901–912Google Scholar
  59. 59.
    Wang Y, Zhang J, Huang ZH, Huang XH, Zheng WB, Yin XF et al (2017) Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop. Cell Death Dis 8:e2876Google Scholar
  60. 60.
    Liu J, Zheng L, Zhong J, Wu N, Liu G, Lin X (2014) Oleanolic acid induces protective autophagy in cancer cells through the JNK and mTOR pathways. Oncol Rep 32:567–572Google Scholar
  61. 61.
    Ma G, Luo W, Lu J, Ma DL, Leung CH, Wang Y et al (2016) Cucurbitacin E induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells. Chem Biol Interact 253:1–9Google Scholar
  62. 62.
    Xu XD, Zhao Y, Zhang M, He RZ, Shi XH, Guo XJ et al (2017) Inhibition of autophagy by deguelin sensitizes pancreatic cancer cells to doxorubicin. Int J Mol Sci 18:370Google Scholar
  63. 63.
    Kim DG, Jung KH, Lee DG, Yoon JH, Choi KS, Kwon SW et al (2014) 20 (S)-Ginsenoside Rg3 is a novel inhibitor of autophagy and sensitizes hepatocellular carcinoma to doxorubicin. Oncotarget 5:54438–51Google Scholar
  64. 64.
    Lao Y, Wan G, Liu Z, Wang X, Ruan P, Xu W et al (2014) The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation. Autophagy 10:736–749Google Scholar
  65. 65.
    Yang C, Wu C, Xu D, Wang M, Xia Q (2016) Astragaloside II inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells. Biomed Pharmacother (Biomedecine pharmacotherapie) 81:166–175Google Scholar
  66. 66.
    Chen L, Ye HL, Zhang G, Yao WM, Chen XZ, Zhang FC et al (2014) Autophagy inhibition contributes to the synergistic interaction between EGCG and doxorubicin to kill the hepatoma Hep3B cells. PLoS One 9:e85771Google Scholar
  67. 67.
    Tan J, Jiang X, Yin G, He L, Liu J, Long Z et al (2017) Anacardic acid induces cell apoptosis of prostatic cancer through autophagy by ER stress/DAPK3/Akt signaling pathway. Oncol Rep 38:1373–1382Google Scholar
  68. 68.
    Li HY, Zhang J, Sun LL, Li BH, Gao HL, Xie T et al (2015) Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: an in vitro and in vivo study. Cell Death Dis 6:e1604Google Scholar
  69. 69.
    Ren G, Sha T, Guo J, Li W, Lu J, Chen X (2015) Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells. J Nat Med 69:522–530Google Scholar
  70. 70.
    Lu T, Gu M, Zhao Y, Zheng X, Xing C (2017) Autophagy contributes to falcarindiol-induced cell death in breast cancer cells with enhanced endoplasmic reticulum stress. PLoS One 12:e0176348Google Scholar
  71. 71.
    Wu M, Lao Y, Xu N, Wang X, Tan H, Fu W et al (2015) Guttiferone K induces autophagy and sensitizes cancer cells to nutrient stressinduced cell death. Phytomedicine 22:902–910Google Scholar
  72. 72.
    Sun ZL, Dong JL, Wu J (2017) Juglanin induces apoptosis and autophagy in human breast cancer progression via ROS/JNK promotion. Biomed Pharmacother 85:303–312Google Scholar
  73. 73.
    Xue L, Zhang WJ, Fan QX, Wang LX (2018) Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells. Oncol Lett 15:1869–1873Google Scholar
  74. 74.
    Tian Y, Xu H, Farooq AA, Nie B, Chen X, Su S, Yuan R et al (2018) Maslinic acid induces autophagy by down-regulating HSPA8 in pancreatic cancer cells. Phytother ResGoogle Scholar
  75. 75.
    Law BYK, Mok SWF, Chen J, Michelangeli F, Jiang ZH, Han Y et al (2017) N-desmethyldauricine induces autophagic cell death in apoptosis-defective cells via Ca2+ mobilization. Front Pharmacol 8:388Google Scholar
  76. 76.
    Chen M, Du Y, Qui M, Wang M, Chen K, Huang Z et al (2013) Ophiopogonin B-induced autophagy in non-small cell lung cancer cells via inhibition of the PI3K/Akt signaling pathway. Oncol Rep 29:430–436Google Scholar
  77. 77.
    Zhao R, Chen M, Jiang Z, Zhao F, Xi B, Zhang X et al (2015) Platycodin-D induced autophagy in non-small cell Lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathways. J Cancer 6:623–631Google Scholar
  78. 78.
    Opipari AW, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR (2004) Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 64:696–703Google Scholar
  79. 79.
    Gong K, Zhang Z, Chen Y, Shu HB, Li W (2014) Extracellular signal-regulated kinase, receptor interacting protein, and reactive oxygen species regulate shikonin-induced autophagy in human hepatocellular carcinoma. Eur J Pharmacol 738:142–152Google Scholar
  80. 80.
    Nagappan A, Lee WS, Yun JW, Lu JN, Chang SH, Jeong JH et al (2017) Tetraarsenic hexoxide induces G2/M arrest, apoptosis, and autophagy via PI3K/Akt suppression and p38 MAPK activation in SW620 human colon cancer cells. PLoS One 12:e0174591Google Scholar
  81. 81.
    Zhang Z, Liu T, Yu M, Li K, Li W (2018) The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent Wnt/β-catenin and metastatic tumor antigen 1 signaling in human liver cancer cells. J Exp Clin Cancer Res 37:7Google Scholar
  82. 82.
    Chen LM, Song TJ, Xiao JH, Huang ZH, Li Y, Lin TY (2017) Tripchlorolide induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR pathway and improves cisplatin sensitivity in A549/DDP cells. Oncotarget 8:63911–63922Google Scholar
  83. 83.
    Xavier CP, Lima CF, Pedro DF, Wilson JM, Kristiansen K, Pereira-Wilson C (2013) Ursolic acid induces cell death and modulates autophagy through JNK pathway in apoptosis-resistant colorectal cancer cells. J Nutr Biochem 24:706–712Google Scholar
  84. 84.
    Geng X, Zhang X, Zhou B, Zhang C, Tu J, Chen X et al (2018) Usnic acid induces cycle arrest, apoptosis, and autophagy in gastric cancer cells in vitro and in vivo. Med Sci Monit 24:556–566Google Scholar
  85. 85.
    Ji L, Zhong B, Jiang X, Mao F, Liu G, Song B et al (2017) Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways. Oncotarget 8:112498–112515Google Scholar
  86. 86.
    Law BY, Wang M, Ma DL, Al-Mousa F, Michelangeli F, Cheng SH et al (2010) Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca (2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis. Mol Cancer Ther 9:718–730Google Scholar
  87. 87.
    Yao Z, Wan Y, Li B, Zhai C, Yao F, Kang Y, Liu Q, Lin D (2018) Berberine induces mitochondrial-mediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCI-H2452 cells. Oncol Rep.  https://doi.org/10.3892/or.2018.6757 Google Scholar
  88. 88.
    Zhu Y, Bu S (2017) Curcumin induces autophagy, apoptosis, and cell cycle arrest in human pancreatic cancer cells. Evid Based Complement Altern Med 2017:5787218Google Scholar
  89. 89.
    Cheng YC, Hueng DY, Huang HY, Chen JY, Chen Y (2016) Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas. Oncotarget 7:29116–29130Google Scholar
  90. 90.
    Hahm ER, Sakao K, Singh SV (2014) Honokiol activates reactive oxygen species-mediated cytoprotective autophagy in human prostate cancer cells. Prostate 74:1209–1221Google Scholar
  91. 91.
    Wu AG1, Wong VK, Xu SW, Chan WK, Ng CI, Liu L et al (2013) Onjisaponin B derived from radix polygalae enhances autophagy and accelerates the degradation of mutant alpha-synuclein and huntingtin in PC-12 Cells. Int J Mol Sci 14:22618–22641Google Scholar
  92. 92.
    Hu H, Chai Y, Wang L, Zhang J, Lee HJ, Kim SH et al (2009) Pentagalloylglucose induces autophagy and caspase-independent programmed deaths in human PC-3 and mouse TRAMP-C2 prostate cancer cells. Mol Cancer Ther 8:2833–2843Google Scholar
  93. 93.
    Wang Y, Zhang W, Lv Q, Zhang J, Zhu D (2016) The critical role of quercetin in autophagy and apoptosis in HeLa cells. Tumour Biol 37:925–929Google Scholar
  94. 94.
    Ramos-Torres Á, Bort A, Morell C, Rodríguez-Henche N, Díaz-Laviada I (2016) The pepper’s natural ingredient capsaicin induces autophagy blockage in prostate cancer cells. Oncotarget 7:1569–1583Google Scholar
  95. 95.
    Zhou J, Li G, Zheng Y, Shen HM, Hu X, Ming QL et al (2015) A novel autophagymitophagy inhibitor liensinine sensitizes breast cancer cells to chemotherapy through DNM1L-mediated mitochondrial fission. Autophagy 11:1259–1279Google Scholar
  96. 96.
    Gewirtz DA (2014) The four faces of autophagy: implications for cancer therapy. Cancer Res 74(3):647–651Google Scholar
  97. 97.
    Bhat P, Kriel J, Priya BS, Salundi B, Shivananju NS, Loos B (2018) Modulating autophagy in cancer therapy: advancements and challenges for cancer cell death sensitization. Biochem Pharmacol 147:170–182Google Scholar
  98. 98.
    Eskelinen EL, Reggiori F, Baba M, Kovács AL, Seglen PO (2011) Seeing is believing: the impact of electron microscopy on autophagy research. Autophagy 7:935–956Google Scholar
  99. 99.
    Orhon I, Reggiori F (2017) Assays to monitor autophagy progression in cell cultures. Cells 6:20Google Scholar
  100. 100.
    Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A et al (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edn). Autophagy 12:1–222Google Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical CollegeGuangzhou University of Chinese MedicineGuangzhouChina
  2. 2.School of Pharmaceutical Sciences, Guangzhou Higher Education Mega CenterGuangzhou University of Chinese MedicineGuangzhouChina

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