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Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine.
Anticancer Res 2016; 36(11):5867-5874AR

Abstract

AIM

To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells.

MATERIALS AND METHODS

We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU).

RESULTS

HAL and FLU co-treatment inhibited the growth and increased apoptosis via G2 arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells.

CONCLUSION

These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells.

Authors+Show Affiliations

School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea hkims@skku.edu syoon88@gmail.com.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea hkims@skku.edu syoon88@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27793910

Citation

Cheon, Ji Hyun, et al. "Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized By Co-treatment With Fluphenazine." Anticancer Research, vol. 36, no. 11, 2016, pp. 5867-5874.
Cheon JH, Lee BM, Kim HS, et al. Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine. Anticancer Res. 2016;36(11):5867-5874.
Cheon, J. H., Lee, B. M., Kim, H. S., & Yoon, S. (2016). Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine. Anticancer Research, 36(11), pp. 5867-5874.
Cheon JH, et al. Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized By Co-treatment With Fluphenazine. Anticancer Res. 2016;36(11):5867-5874. PubMed PMID: 27793910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine. AU - Cheon,Ji Hyun, AU - Lee,Byung Mu, AU - Kim,Hyung Sik, AU - Yoon,Sungpil, PY - 2016/08/11/received PY - 2016/09/02/accepted PY - 2016/10/30/pubmed PY - 2017/2/1/medline PY - 2016/10/30/entrez KW - Halaven KW - P-gp KW - drug-resistance KW - fluphenazine KW - mefloquine KW - thioridazine SP - 5867 EP - 5874 JF - Anticancer research JO - Anticancer Res. VL - 36 IS - 11 N2 - AIM: To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells. MATERIALS AND METHODS: We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU). RESULTS: HAL and FLU co-treatment inhibited the growth and increased apoptosis via G2 arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells. CONCLUSION: These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells. SN - 1791-7530 UR - https://www.unboundmedicine.com/medline/citation/27793910/Highly_Halaven_resistant_KBV20C_Cancer_Cells_Can_Be_Sensitized_by_Co_treatment_with_Fluphenazine_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=27793910 DB - PRIME DP - Unbound Medicine ER -