Acetyl-macrocalin B, an ent-kaurane diterpenoid, initiates apoptosis through the ROS-p38-caspase 9-dependent pathway and induces G2/M phase arrest via the Chk1/2-Cdc25C-Cdc2/cyclin B axis in non-small cell lung cancer

References

• Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: A heterogeneous set of diseases. Nat Rev Cancer. 2014;14:535–46. doi:10.1038/nrc3775. PMID:25056707.
   PubMed Web of Science ®Google Scholar
• Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, Cheney RT, Chirieac LR, D'Amico TA, Dilling TJ, et al. NCCN guidelines insights: Non-small cell lung cancer, version 4.2016. J Natl Compr Canc Netw. 2016;14:255–64. doi:10.6004/jnccn.2016.0031. PMID:26957612.
   PubMed Web of Science ®Google Scholar
• Xiong Y, Huang BY, Yin JY. Pharmacogenomics of platinum-based chemotherapy in non-small cell lung cancer: Focusing on DNA repair systems. Med Oncol. 2017;34:48. doi:10.1007/s12032-017-0905-6. PMID:28215024.
   PubMed Web of Science ®Google Scholar
• Tan WL, Jain A, Takano A, Newell EW, Iyer NG, Lim WT, Tan EH, Zhai W, Hillmer AM, Tam WL, et al. Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. 2016;17:e347–62. doi:10.1016/S1470-2045(16)30123-1. PMID:27511159.
   PubMed Web of Science ®Google Scholar
• D'Addario G, Fruh M, Reck M, Baumann P, Klepetko W, Felip E, Group EGW. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v116–9. doi:10.1093/annonc/mdq189.
   PubMed Web of Science ®Google Scholar
• Tam K, Daly M, Kelly K. Treatment of Locally Advanced Non-Small Cell Lung Cancer. Hematol Oncol Clin North Am. 7;31:45–57. doi:10.1016/j.hoc.2016.08.009.
   Google Scholar
• Mondal S, Bandyopadhyay S, Ghosh MK, Mukhopadhyay S, Roy S, Mandal C. Natural products: Promising resources for cancer drug discovery. Anticancer Agents Med Chem. 2012; 12: 49–75. doi:10.2174/187152012798764697. PMID:21707502.
   PubMed Web of Science ®Google Scholar
• Mishra BB, Tiwari VK. Natural products: An evolving role in future drug discovery. Eur J Med Chem. 2011;46:4769–807. doi:10.1016/j.ejmech.2011.07.057. PMID:21889825.
   PubMed Web of Science ®Google Scholar
• Wan J, Liu M, Jiang HY, Yang J, Du X, Li XN, Wang WG, Li Y, Pu JX, Sun HD. Bioactive ent-kaurane diterpenoids from Isodon serra. Phytochemistry. 2016;130:244–51. doi:10.1016/j.phytochem.2016.05.014. PMID:27298277.
   PubMed Web of Science ®Google Scholar
• Sun HD, Huang SX, Han QB. Diterpenoids from Isodon species and their biological activities. Nat Prod Rep. 2006;23:673–98. doi:10.1039/b604174d. PMID:17003905.
   PubMed Web of Science ®Google Scholar
• Cheng PY, Lin YL, Xu GY. New diterpenoids of rabdosia macrocalyx: the structure of macrocalin A and macrocalin B. Yao Xue Xue Bao. 1984;19:593–8. PMID:6549528.
   PubMedGoogle Scholar
• Hou AJ, Li ML, Jiang B, Lin ZW, Ji SY, Zhou YP, Sun HD. New 7,20:14,20-diepoxy ent-kauranoids from Isodon xerophilus. J Nat Prod. 2000;63:599–601. doi:10.1021/np9903705. PMID:10843567.
   PubMed Web of Science ®Google Scholar
• Yang Y, Sun H, Zhou Y, Ji S, Li M. Effects of three diterpenoids on tumour cell proliferation and telomerase activity. Nat Prod Res. 2009;23:1007–12. doi:10.1080/14786410802295149. PMID:19521915.
   PubMed Web of Science ®Google Scholar
• Yan S, Sorrell M, Berman Z. Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cell Mol Life Sci. 2014;71:3951–67. doi:10.1007/s00018-014-1666-4. PMID:24947324.
   PubMed Web of Science ®Google Scholar
• Park GB, Kim YS, Lee HK, Song H, Kim S, Cho DH, Hur DY. Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells. Cancer Lett. 2011;313:235–48. doi:10.1016/j.canlet.2011.09.011. PMID:22056078.
   PubMed Web of Science ®Google Scholar
• Ma YC, Ke Y, Zi X, Zhao W, Shi XJ, Liu HM. Jaridonin, a novel ent-kaurene diterpenoid from Isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells. Curr Cancer Drug Targets. 2013;13:611–24. doi:10.2174/15680096113139990030. PMID:23597192.
   PubMed Web of Science ®Google Scholar
• Liao YJ, Bai HY, Li ZH, Zou J, Chen JW, Zheng F, Zhang JX, Mai SJ, Zeng MS, Sun HD, et al. Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells. Cell Death Dis. 2014;5:e1137. doi:10.1038/cddis.2014.66. PMID:24651440.
   PubMed Web of Science ®Google Scholar
• Sun X, Wang W, Chen J, Cai X, Yang J, Yang Y, Yan H, Cheng X, Ye J, Lu W, et al. The natural diterpenoid isoforretin a inhibits thioredoxin-1 and triggers potent ros-mediated antitumor effects. Cancer Res. 2017;77:926–36. doi:10.1158/0008-5472.CAN-16-0987. PMID:28011619.
   PubMed Web of Science ®Google Scholar
• Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863:2977–92. doi:10.1016/j.bbamcr.2016.09.012. PMID:27646922.
   PubMed Web of Science ®Google Scholar
• Simon HU, Haj-yehia a and levi-schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2000;5:415–8. doi:10.1023/A:1009616228304. PMID:11256882.
   PubMed Web of Science ®Google Scholar
• Son Y, Cheong YK, Kim NH, Chung HT, Kang DG, Pae HO. Mitogen-activated protein kinases and reactive oxygen species: How can ROS Activate MAPK 7athways? J Signal Transduct. 2011;2011:792639. doi:10.1155/2011/792639. PMID:21637379.
   PubMedGoogle Scholar
• Wu J, Zhang H, Xu Y, Zhang J, Zhu W, Zhang Y, Chen L, Hua W, Mao Y. Juglone induces apoptosis of tumor stem-like cells through ROS-p38 pathway in glioblastoma. BMC Neurol. 2017;17:70. doi:10.1186/s12883-017-0843-0. PMID:28388894.
   PubMed Web of Science ®Google Scholar
• Wang H, Ye Y, Chui JH, Zhu GY, Li YW, Fong DW, Yu ZL. Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells. Oncol Rep. 2010;24:647–51. PMID:20664969.
   PubMed Web of Science ®Google Scholar
• Ma YC, Su N, Shi XJ, Zhao W, Ke Y, Zi X, Zhao NM, Qin YH, Zhao HW, Liu HM. Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway. Toxicol Appl Pharmacol. 2015;282:227–36. doi:10.1016/j.taap.2014.11.003. PMID:25450480.
   PubMed Web of Science ®Google Scholar
• Sun WJ, Huang H, He B, Hu DH, Li PH, Yu YJ, Zhou XH, Lv Z, Zhou L, Hu TY, et al. Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells. Biochem Pharmacol. 2017;127:90–100. doi:10.1016/j.bcp.2016.12.008. PMID:28012958.
   PubMed Web of Science ®Google Scholar
• Landau HJ, McNeely SC, Nair JS, Comenzo RL, Asai T, Friedman H, Jhanwar SC, Nimer SD, Schwartz GK. The checkpoint kinase inhibitor AZD7762 potentiates chemotherapy-induced apoptosis of p53-mutated multiple myeloma cells. Mol Cancer Ther. 2012;11:1781–8. doi:10.1158/1535-7163.MCT-11-0949. PMID:22653969.
   PubMed Web of Science ®Google Scholar
• Dolado I, Swat A, Ajenjo N, De Vita G, Cuadrado A, Nebreda AR. p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis. Cancer Cell. 2007;11:191–205. doi:10.1016/j.ccr.2006.12.013. PMID:17292829.
   PubMed Web of Science ®Google Scholar
• Xu HG, Zhai YX, Chen J, Lu Y, Wang JW, Quan CS, Zhao RX, Xiao X, He Q, Werle KD, et al. LKB1 reduces ROS-mediated cell damage via activation of p38. Oncogene. 2015;34:3848–59. doi:10.1038/onc.2014.315. PMID:25263448.
   PubMed Web of Science ®Google Scholar
• Park SG, Kim SH, Kim KY, Yu SN, Choi HD, Kim YW, Nam HW, Seo YK, Ahn SC. Toyocamycin induces apoptosis via the crosstalk between reactive oxygen species and p38/ERK MAPKs signaling pathway in human prostate cancer PC-3 cells. Pharmacol Rep. 2017;69:90–6. doi:10.1016/j.pharep.2016.10.014. PMID:27912102.
   PubMed Web of Science ®Google Scholar
• Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC. BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet. 2002;30:285–9. doi:10.1038/ng837. PMID:11836499.
   PubMed Web of Science ®Google Scholar
• Busino L, Chiesa M, Draetta GF, Donzelli M. Cdc25A phosphatase: Combinatorial phosphorylation, ubiquitylation and proteolysis. Oncogene. 2004;23:2050–6. doi:10.1038/sj.onc.1207394. PMID:15021892.
   PubMed Web of Science ®Google Scholar
• Rossi A, Sacco PC, Santabarbara G, Sgambato A, Casaluce F, Palazzolo G, Maione P, Gridelli C. Developments in pharmacotherapy for treating metastatic non-small cell lung cancer. Expert Opin Pharmacother. 2017;18:151–63. doi:10.1080/14656566.2017.1280460. PMID:28067062.
   PubMed Web of Science ®Google Scholar
• Deng R, Tang J, Xia LP, Li DD, Zhou WJ, Wang LL, Feng GK, Zeng YX, Gao YH, Zhu XF. ExcisaninA, a diterpenoid compound purified from Isodon MacrocalyxinD, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of its signal pathway. Mol Cancer Ther. 2009;8:873–82. doi:10.1158/1535-7163.MCT-08-1080. PMID:19372560.
   PubMed Web of Science ®Google Scholar
• Liu M, Wang WG, Sun HD, Pu JX. Diterpenoids from isodon species: an update. Nat Prod Rep. 2017;34:1090–140. doi:10.1039/C7NP00027H. PMID:28758169.
   PubMed Web of Science ®Google Scholar
• Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med. 2009;361:1570–83. doi:10.1056/NEJMra0901217. PMID:19828534.
   PubMed Web of Science ®Google Scholar
• Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 2009;9:537–49. doi:10.1038/nrc2694. PMID:19629069.
   PubMed Web of Science ®Google Scholar
• Valdiglesias V, Giunta S, Fenech M, Neri M, Bonassi S. Gammah2ax as a marker of DNA double strand breaks and genomic instability in human population studies. Mutat Res. 2013;753:24–40. doi:10.1016/j.mrrev.2013.02.001. PMID:23416207.
   PubMed Web of Science ®Google Scholar
• Reinhardt HC, Yaffe MB. Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2. Curr Opin Cell Biol. 2009;21:245–55. doi:10.1016/j.ceb.2009.01.018. PMID:19230643.
   PubMed Web of Science ®Google Scholar
• Sur S, Agrawal DK. Phosphatases and kinases regulating CDC25 activity in the cell cycle: Clinical implications of CDC25 overexpression and potential treatment strategies. Mol Cell Biochem. 2016;416:33–46. doi:10.1007/s11010-016-2693-2. PMID:27038604.
   PubMed Web of Science ®Google Scholar
• Smith J, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010;108:73–112. doi:10.1016/B978-0-12-380888-2.00003-0. PMID:21034966.
   PubMed Web of Science ®Google Scholar
• Gavet O, Pines J. Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell. 2010;18:533–43. doi:10.1016/j.devcel.2010.02.013. PMID:20412769.
   PubMed Web of Science ®Google Scholar
• Chou YW, Zhang L, Muniyan S, Ahmad H, Kumar S, Alam SM, Lin MF. Androgens upregulate Cdc25C protein by inhibiting its proteasomal and lysosomal degradation pathways. PLoS One. 2013;8:e61934. doi:10.1371/journal.pone.0061934. PMID:23637932.
   PubMed Web of Science ®Google Scholar
• Thompson R, Meuth M, Woll P, Zhu Y, Danson S. Treatment with the Chk1 inhibitor Go6976 enhances cisplatin cytotoxicity in SCLC cells. Int J Oncol. 2012;40:194–202. PMID:21894433.
   PubMed Web of Science ®Google Scholar
• Reinhardt HC, Aslanian AS, Lees JA, Yaffe MB. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell. 2007;11:175–89. doi:10.1016/j.ccr.2006.11.024. PMID:17292828.
   PubMed Web of Science ®Google Scholar
• Zhang J, Nannapaneni S, Wang D, Liu F, Wang X, Jin R, Liu X, Rahman MA, Peng X, Qian G, et al. Phenformin enhances the therapeutic effect of selumetinib in KRAS-mutant non-small cell lung cancer irrespective of LKB1 status. Oncotarget. 2017;8:59008–22. PMID:28938614.
   PubMedGoogle Scholar
• Yang L, Zhou Y, Li Y, Zhou J, Wu Y, Cui Y, Yang G, Hong Y. Mutations of p53 and KRAS activate NF-kappaB to promote chemoresistance and tumorigenesis via dysregulation of cell cycle and suppression of apoptosis in lung cancer cells. Cancer Lett. 2015;357:520–6. doi:10.1016/j.canlet.2014.12.003. PMID:25499080.
   PubMed Web of Science ®Google Scholar
• Flatmark K, Maelandsmo GM, Martinsen M, Rasmussen H, Fodstad O. Twelve colorectal cancer cell lines exhibit highly variable growth and metastatic capacities in an orthotopic model in nude mice. Eur J Cancer. 2004;40:1593–8. doi:10.1016/j.ejca.2004.02.023. PMID:15196545.
   PubMed Web of Science ®Google Scholar
• Kumar D, Das B, Sen R, Kundu P, Manna A, Sarkar A, Chowdhury C, Chatterjee M, Das P. Andrographolide analogue induces apoptosis and autophagy mediated cell death in U937 Cells by inhibition of PI3K/Akt/mTOR pathway. PLoS One. 2015;10:e0139657. doi:10.1371/journal.pone.0139657. PMID:26436418.
   PubMed Web of Science ®Google Scholar
• Sanceau J, Poupon M-F, Delattre O, Sastre-Garau X, Wietzerbin J. Strong inhibition of ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide. Oncogene. 2002;21:7700. doi:10.1038/sj.onc.1205881. PMID:12400012.
   PubMed Web of Science ®Google Scholar
• Leuraud P, Taillandier L, Medioni J, Aguirre-Cruz L, Criniere E, Marie Y, Kujas M, Golmard JL, Duprez A, Delattre JY, et al. Distinct responses of xenografted gliomas to different alkylating agents are related to histology and genetic alterations. Cancer Res. 2004;64:4648–53. doi:10.1158/0008-5472.CAN-03-3429. PMID:15231677.
   PubMed Web of Science ®Google Scholar
• Guo Q, He J, Shen F, Zhang W, Yang X, Zhang C, Zhang Q, Huang JX, Wu ZD, Sun XC, et al. TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo. Oncol Lett. 2017;13:949–54. doi:10.3892/ol.2016.5515. PMID:28356983.
   PubMed Web of Science ®Google Scholar