Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms

Shahrouz Taranejoo, Mohsen Janmaleki, Mohammad Pachenari, Seyed Morteza Seyedpour, Ramya Chandrasekaran, Wenlong Cheng, Kerry Hourigan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K1 and K2) and the coefficient of viscosity (μ). This difference was more pronounced for cancer cells after 48 h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach.
Original languageEnglish
Pages (from-to)464-472
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume513
Issue number1-2
DOIs
Publication statusPublished - 20 Nov 2016

Keywords

  • Actin microfilaments
  • Albendazole
  • Cancer
  • Cytoskeleton
  • Microtubule-targeting agent
  • Microtubules

Cite this

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title = "Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms",
abstract = "A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K1 and K2) and the coefficient of viscosity (μ). This difference was more pronounced for cancer cells after 48 h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach.",
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author = "Shahrouz Taranejoo and Mohsen Janmaleki and Mohammad Pachenari and Seyedpour, {Seyed Morteza} and Ramya Chandrasekaran and Wenlong Cheng and Kerry Hourigan",
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Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton : Allying dissimilar cell cytoskeleton disrupting mechanisms. / Taranejoo, Shahrouz; Janmaleki, Mohsen; Pachenari, Mohammad; Seyedpour, Seyed Morteza; Chandrasekaran, Ramya; Cheng, Wenlong; Hourigan, Kerry.

In: International Journal of Pharmaceutics, Vol. 513, No. 1-2, 20.11.2016, p. 464-472.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton

T2 - Allying dissimilar cell cytoskeleton disrupting mechanisms

AU - Taranejoo, Shahrouz

AU - Janmaleki, Mohsen

AU - Pachenari, Mohammad

AU - Seyedpour, Seyed Morteza

AU - Chandrasekaran, Ramya

AU - Cheng, Wenlong

AU - Hourigan, Kerry

PY - 2016/11/20

Y1 - 2016/11/20

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KW - Actin microfilaments

KW - Albendazole

KW - Cancer

KW - Cytoskeleton

KW - Microtubule-targeting agent

KW - Microtubules

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DO - 10.1016/j.ijpharm.2016.09.056

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