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

Celina Amaya, Shihua Luo, Julio Baigorri, Rogelio Baucells, Elizabeth R. Smith, Xiang Xi Xu

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Paclitaxel (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). Results: In 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. Conclusions: We 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.

Original languageEnglish (US)
Article number981
JournalBMC Cancer
Volume21
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Breast cancer
  • Cytotoxicity
  • Lysosomal degradation
  • Microtubule
  • Ovarian cancer
  • Taxol/paclitaxel
  • Ultrasound wave

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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