Hyperthermia and radiation reduce the toxic side-effects of bufadienolides for cancer therapy.

Abstract:

:Bufadienolides are constituents of the traditional Chinese medicine Chan Su and are found in toad venom. Cardiovascular side-effects are one of the limiting factors towards developing bufadienolides as chemotherapeutic agents. Thus, in the present study, low doses of bufalin and cinobufotalin, prominent members of the bufadienolides, were investigated for their cytotoxic activity in combination with hyperthermia (HT) or radiation (Rad) therapy. In addition, the underlying mechanism involved was investigated. A DNA fragmentation assay, viability assay and microscopic observation were primarily used to assess the effect of low doses of the two drugs in human lymphoma U937 cells. Furthermore, the effects of these drugs on the mitochondrial membrane potential (MMP) and apoptotic-associated protein activation were investigated. HT/bufadienolide- and RT/bufadienolide-treated samples significantly increased the DNA fragmentation percentile and decreased the MMP, as well as increasing the apoptotic features observed microscopically within a relatively short time (6 h) after treatment. The two combinations affected the expression of important apoptotic markers, including caspase-3 and BH3 interacting domain death agonist. The findings of the current study confirm the additive effect of HT with this group of drugs, directing a novel therapeutic avenue for the clinical use of bufadienolides at lower doses with more restrained cardio toxic side-effects.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Emam H,Refaat A,Jawaid P,Ur Rehman M,Li P,Zhao QL,Kondo T

doi

10.3892/ol.2017.6256

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

1035-1040

issue

1

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-6256

journal_volume

14

pub_type

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