Henley, S. J. et al. Annual Report to the Nation on the Status of Cancer, part I: National cancer statistics. Cancer, https://doi.org/10.1002/cncr.32802 (2020).
Henley, S. J. et al. Annual Report to the Nation on the Status of Cancer, part II: Progress toward Healthy People 2020 objectives for 4 common cancers. Cancer, https://doi.org/10.1002/cncr.32801 (2020).
Lozy, F. & Karantza, V. Autophagy and cancer cell metabolism. Semin. Cell Dev. Biol. 23, 395–401 (2012).
Klionsky, D. J. The molecular machinery of autophagy: unanswered questions. J. Cell Sci. 118, 7–18 (2005).
Mizushima, N. & Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728–741 (2011).
Kroemer, G., Marino, G. & Levine, B. Autophagy and the integrated stress response. Mol. Cell 40, 280–293 (2010).
Yorimitsu, T. & Klionsky, D. J. Autophagy: molecular machinery for self-eating. Cell Death Differ. 12, 1542–1552 (2005).
Klionsky, D. J. A human autophagy interaction network. Autophagy 8, 439–441 (2012).
Yu, L. et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465, 942–946 (2010).
Song, J. et al. Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells. Autophagy 5, 1131–1144 (2009).
Yoon, J. H., Ahn, S. G., Lee, B. H., Jung, S. H. & Oh, S. H. Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1. Biochem. Pharm. 83, 747–757 (2012).
Galluzzi, L. et al. Systems biology of cisplatin resistance: past, present and future. Cell Death Dis. 5, e1257 (2014).
Fridlender, M., Kapulnik, Y. & Koltai, H. Plant derived substances with anti-cancer activity: from folklore to practice. Front Plant Sci. 6, 799 (2015).
Fried, L. E. & Arbiser, J. L. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid. Redox Signal 11, 1139–1148 (2009).
Wolf, I. et al. Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest. Int. J. Oncol. 30, 1529–1537 (2007).
Liu, H. et al. Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer. Eur. J. Pharm. 591, 43–51 (2008).
Park, E. J. et al. Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. Cancer Lett. 277, 133–140 (2009).
Singh, T. & Katiyar, S. K. Honokiol, a phytochemical from Magnolia spp., inhibits breast cancer cell migration by targeting nitric oxide and cyclooxygenase-2. Int. J. Oncol. 38, 769–776 (2011).
Nagalingam, A., Arbiser, J. L., Bonner, M. Y., Saxena, N. K. & Sharma, D. Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Res. 14, R35 (2012).
Avtanski, D. B. et al. Honokiol inhibits epithelial-mesenchymal transition in breast cancer cells by targeting signal transducer and activator of transcription 3/Zeb1/E-cadherin axis. Mol. Oncol. 8, 565–580 (2014).
Avtanski, D. B. et al. Honokiol abrogates leptin-induced tumor progression by inhibiting Wnt1-MTA1-beta-catenin signaling axis in a microRNA-34a dependent manner. Oncotarget 6, 16396–16410 (2015).
Avtanski, D. B. et al. Honokiol activates LKB1-miR-34a axis and antagonizes the oncogenic actions of leptin in breast cancer. Oncotarget 6, 29947–29962 (2015).
Sengupta, S. et al. Activation of tumor suppressor LKB1 by honokiol abrogates cancer stem-like phenotype in breast cancer via inhibition of oncogenic Stat3. Oncogene 36, 5709–5721 (2017).
Green, D. R. & Levine, B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell 157, 65–75 (2014).
Mizushima, N., Yoshimori, T. & Levine, B. Methods in mammalian autophagy research. Cell 140, 313–326 (2010).
Kimura, S., Noda, T. & Yoshimori, T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 3, 452–460 (2007).
Gewirtz, D. A. The four faces of autophagy: implications for cancer therapy. Cancer Res. 74, 647–651 (2014).
Sharma, K., Le, N., Alotaibi, M. & Gewirtz, D. A. Cytotoxic autophagy in cancer therapy. Int. J. Mol. Sci. 15, 10034–10051 (2014).
Gewirtz, D. A. When cytoprotective autophagy isn’t… and even when it is. Autophagy 10, 391–392 (2014).
Wu, Y. T. et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J. Biol. Chem. 285, 10850–10861 (2010).
Rubinsztein, D. C. et al. In search of an “autophagomometer”. Autophagy 5, 585–589 (2009).
Nagelkerke, A., Sweep, F. C., Geurts-Moespot, A., Bussink, J. & Span, P. N. Therapeutic targeting of autophagy in cancer. Part I: molecular pathways controlling autophagy. Semin. Cancer Biol. 31, 89–98 (2015).
Vaahtomeri, K. & Makela, T. P. Molecular mechanisms of tumor suppression by LKB1. FEBS Lett. 585, 944–951 (2011).
Hardie, D. G. New roles for the LKB1–>AMPK pathway. Curr. Opin. cell Biol. 17, 167–173 (2005).
Lu, C. & Xie, C. Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway. Oncol. Rep. 35, 3559–3565 (2016).
Sun, A. et al. GSK-3beta controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells. Prostate 76, 172–183 (2016).
Rink, J., Ghigo, E., Kalaidzidis, Y. & Zerial, M. Rab conversion as a mechanism of progression from early to late endosomes. Cell 122, 735–749 (2005).
Markgraf, D. F., Peplowska, K. & Ungermann, C. Rab cascades and tethering factors in the endomembrane system. FEBS Lett. 581, 2125–2130 (2007).
Fleisher, B., Mody, H., Werkman, C. & Ait-Oudhia, S. Chloroquine sensitizes MDA-MB-231 cells to osimertinib through autophagy-apoptosis crosstalk pathway. Breast Cancer (Dove Med Press) 11, 231–241 (2019).
Gao, L. et al. Histone deacetylase inhibitor trichostatin A and autophagy inhibitor chloroquine synergistically exert anti-tumor activity in H-ras transformed breast epithelial cells. Mol. Med. Rep. 17, 4345–4350 (2018).
Bristol, M. L. et al. Dual functions of autophagy in the response of breast tumor cells to radiation: cytoprotective autophagy with radiation alone and cytotoxic autophagy in radiosensitization by vitamin D 3. Autophagy 8, 739–753 (2012).
Wilson, E. N. et al. A switch between cytoprotective and cytotoxic autophagy in the radiosensitization of breast tumor cells by chloroquine and vitamin D. Hormones Cancer 2, 272–285 (2011).
Kozyreva, V. K. et al. Combination of eribulin and aurora A inhibitor MLN8237 Prevents metastatic colonization and induces cytotoxic autophagy in breast cancer. Mol. Cancer Therapeutics 15, 1809–1822 (2016).
Weng, J. R., Yen, M. H. & Lin, W. Y. Cytotoxic constituents from Celastrus paniculatus induce apoptosis and autophagy in breast cancer cells. Phytochemistry 94, 211–219 (2013).
Chung, S. J. et al. ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy 13, 1386–1403 (2017).
Buchser, W. J., Laskow, T. C., Pavlik, P. J., Lin, H. M. & Lotze, M. T. Cell-mediated autophagy promotes cancer cell survival. Cancer Res. 72, 2970–2979 (2012).
Mathew, R., Karantza-Wadsworth, V. & White, E. Role of autophagy in cancer. Nat. Rev. Cancer 7, 961–967 (2007).
Li, D. D. et al. The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells. Oncogene 28, 886–898 (2009).
Oehadian, A. et al. Differential expression of autophagy in Hodgkin lymphoma cells treated with various anti-cancer drugs. Acta Med. Indones. 39, 153–156 (2007).
Kanzawa, T. et al. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 11, 448–457 (2004).
Wynn, M. L., Consul, N., Merajver, S. D. & Schnell, S. Inferring the effects of honokiol on the notch signaling pathway in SW480 colon cancer cells. Cancer Inf. 13, 1–12 (2014).
Crane, C., Panner, A., Pieper, R. O., Arbiser, J. & Parsa, A. T. Honokiol-mediated inhibition of PI3K/mTOR pathway: a potential strategy to overcome immunoresistance in glioma, breast, and prostate carcinoma without impacting T cell function. J. Immunother. 32, 585–592 (2009).
Zhu, J., Xu, S., Gao, W., Feng, J. & Zhao, G. Honokiol induces endoplasmic reticulum stress-mediated apoptosis in human lung cancer cells. Life Sci. 221, 204–211 (2019).
Wang, J. et al. Hyaluronic acid-modified liposomal honokiol nanocarrier: enhance anti-metastasis and antitumor efficacy against breast cancer. Carbohydr. Polym. 235, 115981 (2020).
Sun, J. et al. Tuning mPEG-PLA/vitamin E-TPGS-based mixed micelles for combined celecoxib/honokiol therapy for breast cancer. Eur. J. Pharm. Sci. 146, 105277 (2020).
Liu, H. T. et al. Nanoparticulated honokiol mitigates cisplatin-induced chronic kidney injury by maintaining mitochondria antioxidant capacity and reducing Caspase 3-associated cellular apoptosis. Antioxidants (Basel) 8, 466 (2019).
Wu, Q., Zhang, M., Luo, H. & Yi, T. Self-assembled honokiol-loaded microbubbles in the treatment of ovarian cancer by ultrasound irradiation. J. Biomed. Nanotechnol. 14, 1796–1805 (2018).
Kullmann, L. & Krahn, M. P. Controlling the master-upstream regulation of the tumor suppressor LKB1. Oncogene 37, 3045–3057 (2018).
Jin, P. et al. MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling. Cell Death Dis. 10, 615 (2019).
Li, F. et al. BET inhibitor JQ1 suppresses cell proliferation via inducing autophagy and activating LKB1/AMPK in bladder cancer cells. Cancer Med. 8, 4792–4805 (2019).
Woods, A. et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr. Biol. 13, 2004–2008 (2003).
Zeng, P. Y. & Berger, S. L. LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation. Cancer Res. 66, 10701–10708 (2006).
Bousquet, G. et al. Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple negative breast cancer. Oncotarget 8, 35205–35221 (2017).
Hu, J. et al. ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine. J. Exp. Clin. Cancer Res. 38, 225 (2019).
Masuelli, L. et al. Chloroquine supplementation increases the cytotoxic effect of curcumin against Her2/neu overexpressing breast cancer cells in vitro and in vivo in nude mice while counteracts it in immune competent mice. Oncoimmunology 6, e1356151 (2017).
Lefort, S. et al. Inhibition of autophagy as a new means of improving chemotherapy efficiency in high-LC3B triple-negative breast cancers. Autophagy 10, 2122–2142 (2014).
Zhang, X. et al. Enhancing therapeutic effects of docetaxel-loaded dendritic copolymer nanoparticles by co-treatment with autophagy inhibitor on breast cancer. Theranostics 4, 1085–1095 (2014).
Mahalingam, D. et al. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy 10, 1403–1414 (2014).
Rangwala, R. et al. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy 10, 1391–1402 (2014).
Vogl, D. T. et al. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy 10, 1380–1390 (2014).
Guo, W., Wang, Y., Wang, Z., Wang, Y. P. & Zheng, H. Inhibiting autophagy increases epirubicin’s cytotoxicity in breast cancer cells. Cancer Sci. 107, 1610–1621 (2016).
Sun, R. et al. Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells. Biomaterials 103, 44–55 (2016).
Zhang, P. et al. w09, a novel autophagy enhancer, induces autophagy-dependent cell apoptosis via activation of the EGFR-mediated RAS-RAF1-MAP2K-MAPK1/3 pathway. Autophagy 13, 1093–1112 (2017).
Shan, C. et al. Discovery of novel autophagy inhibitors and their sensitization abilities for vincristine-resistant esophageal cancer cell line Eca109/VCR. ChemMedChem https://doi.org/10.1002/cmdc.202000004 (2020).
Kinzler, M. N. et al. STF-62247 and pimozide induce autophagy and autophagic cell death in mouse embryonic fibroblasts. Sci. Rep. 10, 687 (2020).
Bai, X. et al. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J. Biol. Chem. 278, 35501–35507 (2003).
Muniraj, N. et al. Withaferin A inhibits lysosomal activity to block autophagic flux and induces apoptosis via energetic impairment in breast cancer cells. Carcinogenesis, https://doi.org/10.1093/carcin/bgz015 (2019).
Siddharth, S., Muniraj, N., Saxena, N. K. & Sharma, D. Concomitant inhibition of cytoprotective autophagy augments the efficacy of withaferin a in hepatocellular carcinoma. Cancers (Basel) 11, 453 (2019).
Yan, D., Avtanski, D., Saxena, N. K. & Sharma, D. Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires beta-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. J. Biol. Chem. 287, 8598–8612 (2012).
Taliaferro-Smith, L. et al. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene 28, 2621–2633 (2009).