Induction of STK11-dependent cytoprotective autophagy in breast cancer cells upon honokiol treatment


  • 1.

    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).

  • 2.

    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).

  • 3.

    Lozy, F. & Karantza, V. Autophagy and cancer cell metabolism. Semin. Cell Dev. Biol. 23, 395–401 (2012).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 4.

    Klionsky, D. J. The molecular machinery of autophagy: unanswered questions. J. Cell Sci. 118, 7–18 (2005).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 5.

    Mizushima, N. & Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728–741 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • 6.

    Kroemer, G., Marino, G. & Levine, B. Autophagy and the integrated stress response. Mol. Cell 40, 280–293 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 7.

    Yorimitsu, T. & Klionsky, D. J. Autophagy: molecular machinery for self-eating. Cell Death Differ. 12, 1542–1552 (2005).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 8.

    Klionsky, D. J. A human autophagy interaction network. Autophagy 8, 439–441 (2012).

    PubMed 

    Google Scholar
     

  • 9.

    Yu, L. et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465, 942–946 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 10.

    Song, J. et al. Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells. Autophagy 5, 1131–1144 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 11.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 12.

    Galluzzi, L. et al. Systems biology of cisplatin resistance: past, present and future. Cell Death Dis. 5, e1257 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 13.

    Fridlender, M., Kapulnik, Y. & Koltai, H. Plant derived substances with anti-cancer activity: from folklore to practice. Front Plant Sci. 6, 799 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 14.

    Fried, L. E. & Arbiser, J. L. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxid. Redox Signal 11, 1139–1148 (2009).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 15.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 16.

    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).

    CAS 

    Google Scholar
     

  • 17.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 18.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 19.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 20.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 21.

    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).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 22.

    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).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 23.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 24.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 25.

    Mizushima, N., Yoshimori, T. & Levine, B. Methods in mammalian autophagy research. Cell 140, 313–326 (2010).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 26.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 27.

    Gewirtz, D. A. The four faces of autophagy: implications for cancer therapy. Cancer Res. 74, 647–651 (2014).

    CAS 
    PubMed 

    Google Scholar
     

  • 28.

    Sharma, K., Le, N., Alotaibi, M. & Gewirtz, D. A. Cytotoxic autophagy in cancer therapy. Int. J. Mol. Sci. 15, 10034–10051 (2014).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 29.

    Gewirtz, D. A. When cytoprotective autophagy isn’t… and even when it is. Autophagy 10, 391–392 (2014).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 30.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 31.

    Rubinsztein, D. C. et al. In search of an “autophagomometer”. Autophagy 5, 585–589 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 32.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 33.

    Vaahtomeri, K. & Makela, T. P. Molecular mechanisms of tumor suppression by LKB1. FEBS Lett. 585, 944–951 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • 34.

    Hardie, D. G. New roles for the LKB1–>AMPK pathway. Curr. Opin. cell Biol. 17, 167–173 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • 35.

    Lu, C. & Xie, C. Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway. Oncol. Rep. 35, 3559–3565 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 36.

    Sun, A. et al. GSK-3beta controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells. Prostate 76, 172–183 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 37.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 38.

    Markgraf, D. F., Peplowska, K. & Ungermann, C. Rab cascades and tethering factors in the endomembrane system. FEBS Lett. 581, 2125–2130 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • 39.

    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).

    CAS 

    Google Scholar
     

  • 40.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 41.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 42.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 43.

    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).

    CAS 

    Google Scholar
     

  • 44.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 45.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 46.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 47.

    Mathew, R., Karantza-Wadsworth, V. & White, E. Role of autophagy in cancer. Nat. Rev. Cancer 7, 961–967 (2007).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 48.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 49.

    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).

    PubMed 

    Google Scholar
     

  • 50.

    Kanzawa, T. et al. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ. 11, 448–457 (2004).

    CAS 
    PubMed 

    Google Scholar
     

  • 51.

    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).


    Google Scholar
     

  • 52.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 53.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 54.

    Wang, J. et al. Hyaluronic acid-modified liposomal honokiol nanocarrier: enhance anti-metastasis and antitumor efficacy against breast cancer. Carbohydr. Polym. 235, 115981 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • 55.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 56.

    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).

    CAS 

    Google Scholar
     

  • 57.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 58.

    Kullmann, L. & Krahn, M. P. Controlling the master-upstream regulation of the tumor suppressor LKB1. Oncogene 37, 3045–3057 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • 59.

    Jin, P. et al. MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling. Cell Death Dis. 10, 615 (2019).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 60.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 61.

    Woods, A. et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr. Biol. 13, 2004–2008 (2003).

    CAS 
    PubMed 

    Google Scholar
     

  • 62.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 63.

    Bousquet, G. et al. Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple negative breast cancer. Oncotarget 8, 35205–35221 (2017).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 64.

    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).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 65.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 66.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 67.

    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).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 68.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 69.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 70.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 71.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 72.

    Sun, R. et al. Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells. Biomaterials 103, 44–55 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 73.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 74.

    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).

  • 75.

    Kinzler, M. N. et al. STF-62247 and pimozide induce autophagy and autophagic cell death in mouse embryonic fibroblasts. Sci. Rep. 10, 687 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 76.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 77.

    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).

  • 78.

    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).

    CAS 
    PubMed Central 

    Google Scholar
     

  • 79.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 80.

    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).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     



  • Source link

    Leave a Reply

    Your email address will not be published. Required fields are marked *