Modulation of doxorubicin activity in cancer cells by conjugation with fatty acyl and terpenyl hydrazones

European Journal of Medicinal Chemistry
Katharina EffenbergerRainer Schobert

Abstract

Doxorubicin N-acylhydrazones derived from saturated, unsaturated and terpene-terminated fatty acids were tested for anticancer activity in cells of human HL-60 leukaemia, 518A2 melanoma, MCF-7/Topo breast and KB-V1/Vbl cervix carcinomas. In the latter, the N-heptadecanoyl hydrazone was more cytotoxic than its unsaturated C18-fatty acyl analogues and even three times more than doxorubicin. The (menthoxycarbonyl)undecanoyl hydrazone was twice as active as doxorubicin in these multidrug resistant KB-V1/Vbl and in the 518A2 cells and also more efficacious in KB-V1 and MCF-7 cells that had been desensitised for doxorubicin. All hydrazones induced apoptosis albeit by slightly different mechanisms. While apoptosis induction by the menthoxymalonyl hydrazone was characterized by an upfront increase in caspase-8 activity, all other hydrazones elicited a hike in caspase-9 activity. Treatment of HL-60 and 518A2 cells with doxorubicin or its heptadecanoyl, linolenoyl, (menthoxycarbonyl)undecanoyl or menthoxymalonyl hydrazones also led to diverging increases of the ratio of bax to bcl-2 mRNA expression, of reactive oxygen species and of mitochondrial membrane damage.

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Citations

Jun 29, 2010·Cancer Chemotherapy and Pharmacology·Katharina Effenberger-Neidnicht, Rainer Schobert
May 25, 2011·Cancer Chemotherapy and Pharmacology·Katharina Effenberger-NeidnichtRainer Schobert
Apr 12, 2014·Molecular Pharmaceutics·Chun-Hui LiangSi-Yuan Zhou
Nov 11, 2014·International Journal of Medicinal Chemistry·Anu KajalVipin Saini
Jul 27, 2015·Biochimie·Céline CrausteJoseph Vercauteren
Jan 13, 2017·Molecular Pharmaceutics·Danielle IrbyFeng Li
Apr 11, 2019·Mini Reviews in Medicinal Chemistry·Pelin Çıkla-Süzgün, Ş Güniz Küçükgüzel
Jan 7, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Sanchari DasguptaDebasis Das
Feb 12, 2020·Drug Metabolism Reviews·Hanlan LiuChandra Prakash
Aug 11, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Thangavel Sathiya KamatchiJan Grzegorz Małecki
Jan 6, 2019·AAPS PharmSciTech·Tushar DateSanyog Jain
Jan 21, 2020·European Journal of Pharmacology·Michał JóźwiakMarta Struga
May 6, 2021·International Journal of Molecular Sciences·Mariola Zielińska-BłajetJoanna Feder-Kubis
Feb 26, 2015·Langmuir : the ACS Journal of Surfaces and Colloids·Stephanie J MattinglyMichael H Nantz

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