Quinacrine in endometrial cancer: Repurposing an old antimalarial drug

Eleftheria Kalogera, Debarshi Roy, Ashwani Khurana, Susmita Mondal, Amy L. Weaver, Xiaoping He, Sean Christopher Dowdy, Vijayalakshmi Shridhar

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective Generate preclinical data on the effect of quinacrine (QC) in inhibiting tumorigenesis in endometrial cancer (EC) in vitro and explore its role as an adjunct to standard chemotherapy in an EC mouse model. Methods Five different EC cell lines (Ishikawa, Hec-1B, KLE, ARK-2, and SPEC-2) representing different histologies, grades of EC, sensitivity to cisplatin and p53 status were used for the in vitro studies. MTT and colony formation assays were used to examine QC's ability to inhibit cell viability in vitro. The Chou-Talalay methodology was used to examine synergism between QC and cisplatin, carboplatin or paclitaxel. A cisplatin-resistant EC subcutaneous mouse model (Hec-1B) was used to examine QC's role as maintenance therapy. Results QC exhibited strong synergism in vitro when combined with cisplatin, carboplatin or paclitaxel with the highest level of synergism in the most chemo-resistant cell line. Neither QC monotherapy nor carboplatin/paclitaxel significantly delayed tumor growth in xenografts. Combination treatment (QC plus carboplatin/paclitaxel) significantly augmented the antiproliferative ability of these agents and was associated with a 14-week survival prolongation compared to carboplatin/paclitaxel. Maintenance with QC resulted in further delay in tumor progression and survival prolongation compared to carboplatin/paclitaxel. QC was not associated with weight loss and the yellow skin discoloration noted during treatment was reversible upon discontinuation. Conclusions QC exhibited significant antitumor activity against EC in vitro and was successful as maintenance therapy in chemo-resistant EC mouse xenografts. This preclinical data suggest that QC may be an important adjunct to standard chemotherapy for patients with chemo-resistant EC.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalGynecologic Oncology
Volume146
Issue number1
DOIs
StatePublished - Jul 1 2017

Fingerprint

Quinacrine
Antimalarials
Endometrial Neoplasms
Carboplatin
Paclitaxel
Cisplatin
Heterografts
Drug Therapy
Cell Line
Survival
Therapeutics
Weight Loss
Neoplasms
Cell Survival
Histology
Carcinogenesis
Maintenance
In Vitro Techniques
Skin

Keywords

  • Chemoresistance
  • Endometrial cancer
  • Quinacrine
  • Survival
  • Synergy

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Quinacrine in endometrial cancer : Repurposing an old antimalarial drug. / Kalogera, Eleftheria; Roy, Debarshi; Khurana, Ashwani; Mondal, Susmita; Weaver, Amy L.; He, Xiaoping; Dowdy, Sean Christopher; Shridhar, Vijayalakshmi.

In: Gynecologic Oncology, Vol. 146, No. 1, 01.07.2017, p. 187-195.

Research output: Contribution to journalArticle

Kalogera E, Roy D, Khurana A, Mondal S, Weaver AL, He X et al. Quinacrine in endometrial cancer: Repurposing an old antimalarial drug. Gynecologic Oncology. 2017 Jul 1;146(1):187-195. https://doi.org/10.1016/j.ygyno.2017.04.022
Kalogera, Eleftheria ; Roy, Debarshi ; Khurana, Ashwani ; Mondal, Susmita ; Weaver, Amy L. ; He, Xiaoping ; Dowdy, Sean Christopher ; Shridhar, Vijayalakshmi. / Quinacrine in endometrial cancer : Repurposing an old antimalarial drug. In: Gynecologic Oncology. 2017 ; Vol. 146, No. 1. pp. 187-195.
@article{5350eb8a246640919feb388a366cfaf6,
title = "Quinacrine in endometrial cancer: Repurposing an old antimalarial drug",
abstract = "Objective Generate preclinical data on the effect of quinacrine (QC) in inhibiting tumorigenesis in endometrial cancer (EC) in vitro and explore its role as an adjunct to standard chemotherapy in an EC mouse model. Methods Five different EC cell lines (Ishikawa, Hec-1B, KLE, ARK-2, and SPEC-2) representing different histologies, grades of EC, sensitivity to cisplatin and p53 status were used for the in vitro studies. MTT and colony formation assays were used to examine QC's ability to inhibit cell viability in vitro. The Chou-Talalay methodology was used to examine synergism between QC and cisplatin, carboplatin or paclitaxel. A cisplatin-resistant EC subcutaneous mouse model (Hec-1B) was used to examine QC's role as maintenance therapy. Results QC exhibited strong synergism in vitro when combined with cisplatin, carboplatin or paclitaxel with the highest level of synergism in the most chemo-resistant cell line. Neither QC monotherapy nor carboplatin/paclitaxel significantly delayed tumor growth in xenografts. Combination treatment (QC plus carboplatin/paclitaxel) significantly augmented the antiproliferative ability of these agents and was associated with a 14-week survival prolongation compared to carboplatin/paclitaxel. Maintenance with QC resulted in further delay in tumor progression and survival prolongation compared to carboplatin/paclitaxel. QC was not associated with weight loss and the yellow skin discoloration noted during treatment was reversible upon discontinuation. Conclusions QC exhibited significant antitumor activity against EC in vitro and was successful as maintenance therapy in chemo-resistant EC mouse xenografts. This preclinical data suggest that QC may be an important adjunct to standard chemotherapy for patients with chemo-resistant EC.",
keywords = "Chemoresistance, Endometrial cancer, Quinacrine, Survival, Synergy",
author = "Eleftheria Kalogera and Debarshi Roy and Ashwani Khurana and Susmita Mondal and Weaver, {Amy L.} and Xiaoping He and Dowdy, {Sean Christopher} and Vijayalakshmi Shridhar",
year = "2017",
month = "7",
day = "1",
doi = "10.1016/j.ygyno.2017.04.022",
language = "English (US)",
volume = "146",
pages = "187--195",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Quinacrine in endometrial cancer

T2 - Repurposing an old antimalarial drug

AU - Kalogera, Eleftheria

AU - Roy, Debarshi

AU - Khurana, Ashwani

AU - Mondal, Susmita

AU - Weaver, Amy L.

AU - He, Xiaoping

AU - Dowdy, Sean Christopher

AU - Shridhar, Vijayalakshmi

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Objective Generate preclinical data on the effect of quinacrine (QC) in inhibiting tumorigenesis in endometrial cancer (EC) in vitro and explore its role as an adjunct to standard chemotherapy in an EC mouse model. Methods Five different EC cell lines (Ishikawa, Hec-1B, KLE, ARK-2, and SPEC-2) representing different histologies, grades of EC, sensitivity to cisplatin and p53 status were used for the in vitro studies. MTT and colony formation assays were used to examine QC's ability to inhibit cell viability in vitro. The Chou-Talalay methodology was used to examine synergism between QC and cisplatin, carboplatin or paclitaxel. A cisplatin-resistant EC subcutaneous mouse model (Hec-1B) was used to examine QC's role as maintenance therapy. Results QC exhibited strong synergism in vitro when combined with cisplatin, carboplatin or paclitaxel with the highest level of synergism in the most chemo-resistant cell line. Neither QC monotherapy nor carboplatin/paclitaxel significantly delayed tumor growth in xenografts. Combination treatment (QC plus carboplatin/paclitaxel) significantly augmented the antiproliferative ability of these agents and was associated with a 14-week survival prolongation compared to carboplatin/paclitaxel. Maintenance with QC resulted in further delay in tumor progression and survival prolongation compared to carboplatin/paclitaxel. QC was not associated with weight loss and the yellow skin discoloration noted during treatment was reversible upon discontinuation. Conclusions QC exhibited significant antitumor activity against EC in vitro and was successful as maintenance therapy in chemo-resistant EC mouse xenografts. This preclinical data suggest that QC may be an important adjunct to standard chemotherapy for patients with chemo-resistant EC.

AB - Objective Generate preclinical data on the effect of quinacrine (QC) in inhibiting tumorigenesis in endometrial cancer (EC) in vitro and explore its role as an adjunct to standard chemotherapy in an EC mouse model. Methods Five different EC cell lines (Ishikawa, Hec-1B, KLE, ARK-2, and SPEC-2) representing different histologies, grades of EC, sensitivity to cisplatin and p53 status were used for the in vitro studies. MTT and colony formation assays were used to examine QC's ability to inhibit cell viability in vitro. The Chou-Talalay methodology was used to examine synergism between QC and cisplatin, carboplatin or paclitaxel. A cisplatin-resistant EC subcutaneous mouse model (Hec-1B) was used to examine QC's role as maintenance therapy. Results QC exhibited strong synergism in vitro when combined with cisplatin, carboplatin or paclitaxel with the highest level of synergism in the most chemo-resistant cell line. Neither QC monotherapy nor carboplatin/paclitaxel significantly delayed tumor growth in xenografts. Combination treatment (QC plus carboplatin/paclitaxel) significantly augmented the antiproliferative ability of these agents and was associated with a 14-week survival prolongation compared to carboplatin/paclitaxel. Maintenance with QC resulted in further delay in tumor progression and survival prolongation compared to carboplatin/paclitaxel. QC was not associated with weight loss and the yellow skin discoloration noted during treatment was reversible upon discontinuation. Conclusions QC exhibited significant antitumor activity against EC in vitro and was successful as maintenance therapy in chemo-resistant EC mouse xenografts. This preclinical data suggest that QC may be an important adjunct to standard chemotherapy for patients with chemo-resistant EC.

KW - Chemoresistance

KW - Endometrial cancer

KW - Quinacrine

KW - Survival

KW - Synergy

UR - http://www.scopus.com/inward/record.url?scp=85019587256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019587256&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2017.04.022

DO - 10.1016/j.ygyno.2017.04.022

M3 - Article

C2 - 28545688

AN - SCOPUS:85019587256

VL - 146

SP - 187

EP - 195

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 1

ER -