Paclitaxel is a chemotherapeutic drug for cancer, which is isolated from the Pacific yew tree. However, and the molecular mechanism and the antitumor effects of paclitaxel on osteosarcoma cell remain to be explored.
The aim of our study was to explore the possible molecular mechanisms of apoptosis in osteosarcoma induced by paclitaxel.
Paclitaxel can obviously decrease the proliferation of HOS-732 cells in a dose-dependent manner. Paclitaxel could induce the cell cycle arrest at the G2/M-phase and decreases the CDK5 and CCNE1 expression in HOS-732 cells. Paclitaxel promotes cell apoptosis in HOS-732 cells, which may be contacted to the decreasing of Bcl-2 protein expression. Further, the production of ROS in HOS-732 cells was remarkably increased with the increasing concentration of paclitaxel. Moreover, paclitaxel induces the ER-stress related gene and protein expression (GRP79, DDIT3 mRNA and GRP78, XBP-1 s, IRE1α protein expression) in osteosarcoma cells.
Paclitaxel can inhibit the proliferation of HOS-732 cells and increase ROS and ER-stress response to promote cell apoptosis, suggesting that paclitaxel may represent a new therapeutic option for the treatment and prevention osteosarcoma.
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Almanza A, Carlesso A, Chintha C, Creedican S, Doultsinos D, Leuzzi B, Luís A, McCarthy N, Montibeller L, More S, Papaioannou A, Püschel F, Sassano ML, Skoko J, Agostinis P, de Belleroche J, Eriksson LA, Fulda S, Gorman AM, Healy S, Kozlov A, Muñoz-Pinedo C, Rehm M, Chevet E, Samali A (2019) Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications. FEBS J 286:241–278
Chen C, Hu H, Qiao M, Zhao X, Wang Y, Chen K, Chen D (2015) Anti-tumor activity of paclitaxel through dual-targeting lipoprotein-mimicking nanocarrier. J Drug Target 23:311–322
Cubillos-Ruiz JR, Bettigole SE, Glimcher LH (2017) Tumorigenic and immunosuppressive effects of endoplasmic reticulum stress in cancer. Cell 168:692–706
Feng J, Shu R, Ning L et al (2017) Synergistic antitumor effects of berbamine and paclitaxel through ROS/Akt pathway in glioma cells. Evid Based Complement Altern Med 2017:1–8
Gibbs CP Jr, Weber K, Scarborough MT (2002) Malignant bone tumors. Instr Course Lect 51:413–428
Goldman JW, Waterhouse DM, George B, O’Dwyer PJ, Bhore R, Banerjee S, Lyons L, Louis CU, Ong TJ, Kelly K (2019) Safety and efficacy results of a phase I, open-label study of concurrent and delayed nivolumab in combination with nab-paclitaxel and carboplatin in advanced non-small cell lung cancer. Front Oncol 9:1256
Hu J, Zhang NA, Wang R, Huang F, Li G (2015) Paclitaxel induces apoptosis and reduces proliferation by targeting epidermal growth factor receptor signaling pathway in oral cavity squamous cell carcinoma. Oncol Lett 10:2378–2384
Ingham M, Schwartz GK (2017) Biology of neoplasia: cell-cycle therapeutics come of age. J Clin Oncol 35:2949–2959
Javeed A, Ashraf M, Riaz A, Ghafoor A, Afzal S, Mukhtar MM (2009) Paclitaxel and immune system. Eur J Pharm Sci 38:283–290
Kawiak A, Piosik J, Stasilojc G, Gwizdek-Wisniewska A, Marczak L, Stobiecki M, Bigda J, Lojkowska E (2007) Induction of apoptosis by plumbagin through reactive oxygen species-mediated inhibition of topoisomerase II. Toxicol Appl Pharmacol 223:267–276
Kim SJ, Hwang SG, Shin DY, Kang SS, Chun JS (2002) p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFκB-dependent transcription and stabilization by serine 15 phosphorylation. J Biol Chem 277:33501–33508
Martino C, Pandya D, Lee R, Levy G, Lo T, Lobo S, Frank RC (2020) ATM-mutated pancreatic cancer: clinical and molecular response to gemcitabine/nab-paclitaxel after genome-based therapy resistance. Pancreas 49:143–147
Mcguire J, Utset-Ward TJ, Reed DR, Lynch CC (2017) Re-calculating! Navigating through the osteosarcoma treatment roadblock. Pharmacol Res 117:54–64
Moloney JN, Cotter TG (2018) ROS signalling in the biology of cancer. Semin Cell Dev Biol 80:50–64
Morales-Cano D, Calviño E, Rubio V, Herráez A, Sancho P, Tejedor MC, Diez JC (2013) Apoptosis induced by paclitaxel via Bcl-2, Bax and caspases 3 and 9 activation in NB4 human leukaemia cells is not modulated by ERK inhibition. Exp Toxicol Pathol 65:1101–1108
Otsuka R, Iwasa S, Yanai T et al (2020) Impact of peripheral neuropathy induced by platinum in first-line chemotherapy on second-line chemotherapy with paclitaxel for advanced gastric cancer. Int J Clin Oncol 25(4):595–601
Saad AM, Abdel-Rahman O (2019) Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases. Expert Opin Pharmacother 20:1767–1775
Schmid P, Abraham J, Chan S et al (2020) Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol 38(5):423–433
Shakhwar S, Darwish R, Kamal MM, Nazzal S, Pallerla S, Abu Fayyad A (2020) Development and evaluation of paclitaxel nanoemulsion for cancer therapy. Pharm Dev Technol 25(4):510–516
Son Y, Cheong YK, Kim NH, Chung HT, Kang DG, Pae HO (2011) Mitogen-activated protein kinases and reactive oxygen species: how can ROS activate MAPK pathways? J Signal Transduct 2011:792639
Sorokina O, Goryanin I (2012) Preface. Eur J Pharm Sci 46:189
Vos HI, Coenen MJ, Guchelaar HJ, Te Loo DM (2016) The role of pharmacogenetics in the treatment of osteosarcoma. Drug Discov Today 21:1775–1786
Wang H, Li D, Li X, Ou X, Liu S, Zhang Y, Ding J, Xie B (2016) Mammalian target of rapamycin inhibitor RAD001 sensitizes endometrial cancer cells to paclitaxel-induced apoptosis via the induction of autophagy. Oncol Lett 12:5029–5035
Weng CS, Wu CC, Chen TC, Chen JR, Huang CY, Chang CL (2015) Retrospective analysis of comparative outcomes in recurrent platinum-sensitive ovarian cancer treated with pegylated liposomal doxorubicin (Lipo-Dox) and carboplatin versus paclitaxel and carboplatin. Eur J Cancer 51:352–358
Xu R, Sato N, Yanai K, Akiyoshi T, Nagai S, Wada J, Koga K, Mibu R, Nakamura M, Katano M (2009) Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells. Anticancer Res 29:261–270
Yang C, Lim W, Bazer FW, Song G (2017) Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress. Cancer Lett 399:10–19
Zhang X, Huang J, Yu C et al (2020) Quercetin enhanced paclitaxel therapeutic effects towards PC-3 prostate cancer through ER stress induction and ROS production. Oncotargets Ther 13:513–523
Zhong Y, Su T, Shi Q, Feng Y, Tao Z, Huang Q, Li L, Hu L, Li S, Tan H, Liu S, Yang H (2019) Co-administration of iRGD enhances tumor-targeted delivery and anti-tumor effects of paclitaxel-loaded PLGA nanoparticles for colorectal cancer treatment. Int J Nanomed 14:8543–8560
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The authors declare that they no competing inerests.
Approval for the present study was obtained by the Ethics Committee of the first people’s hospital of Wenling (Zhengjiang, China).
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Li, M., Yin, L., Wu, L. et al. Paclitaxel inhibits proliferation and promotes apoptosis through regulation ROS and endoplasmic reticulum stress in osteosarcoma cell. Mol. Cell. Toxicol. (2020). https://doi.org/10.1007/s13273-020-00093-7
- Reactive oxygen species