Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells

BMC Cancer

Elizabeth R. Smith¹  Celina Amaya²  Shihua Luo²  Xiang-Xi Xu²  Julio Baigorri³  Rogelio Baucells³ 

[1] Department of Cell Biology, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Papanicolaou Building, Room 415 [M877], 1550 NW 10th Avenue, 33136, Miami, FL, USA;HHMI High School Scholars Program, Department of Undergraduate Research and Community Outreach, University of Miami, 33146, Miami, FL, USA;

关键词: Ultrasound wave;    Microtubule;    Taxol/paclitaxel;    Cytotoxicity;    Lysosomal degradation;    Ovarian cancer;    Breast cancer;   

DOI  :  10.1186/s12885-021-08722-7

来源: Springer

【 摘 要 】

BackgroundPaclitaxel (Taxol) is a microtubule-stabilizing drug used to treat several solid tumors, including ovarian, breast, non-small cell lung, and pancreatic cancers. The current treatment of ovarian cancer is chemotherapy using paclitaxel in combination with carboplatin as a frontline agent, and paclitaxel is also used in salvage treatment as a second line drug with a dose intensive regimen following recurrence. More recently, a dose dense approach for paclitaxel has been used to treat metastatic breast cancer with success.Paclitaxel binds to beta tubulin with high affinity and stabilizes microtubule bundles. As a consequence of targeting microtubules, paclitaxel kills cancer cells through inhibition of mitosis, causing mitotic catastrophes, and by additional, not yet well defined non-mitotic mechanism(s).ResultsIn exploring methods to modulate activity of paclitaxel in causing cancer cell death, we unexpectedly found that a brief exposure of paclitaxel-treated cells in culture to low intensity ultrasound waves prevented the paclitaxel-induced cytotoxicity and death of the cancer cells. The treatment with ultrasound shock waves was found to transiently disrupt the microtubule cytoskeleton and to eliminate paclitaxel-induced rigid microtubule bundles. When cellular microtubules were labelled with a fluorescent paclitaxel analog, exposure to ultrasound waves led to the disassembly of the labeled microtubules and localization of the signals to perinuclear compartments, which were determined to be lysosomes.ConclusionsWe suggest that ultrasound disrupts the paclitaxel-induced rigid microtubule cytoskeleton, generating paclitaxel bound fragments that undergo degradation. A new microtubule network forms from tubulins that are not bound by paclitaxel. Hence, ultrasound shock waves are able to abolish paclitaxel impact on microtubules.Thus, our results demonstrate that a brief exposure to low intensity ultrasound can reduce and/or eliminate cytotoxicity associated with paclitaxel treatment of cancer cells in cultures.

【 授权许可】

CC BY