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14P - Butein inhibits solid tumors cell viability, colony, and tumor growth via STAT3 signaling pathway and enhance the anti-cancer effects of Frondoside-A and camptothecin (ID 190)

Presentation Number
14P
Lecture Time
18:25 - 18:25
Speakers
  • S. Attoub
Location
Hall Bordeaux, Palais des Congr├Ęs, Paris, France
Date
26.02.2019
Time
18:00 - 18:45
Authors
  • S. Attoub
  • S. Sulaiman
  • K. Arafat

Abstract

Background

Despite the major recent advances in cancer management, cure of cancer remains a serious challenge.

Methods

In the current study, we investigated the impact of butein, a biologically active flavonoid, on the human cancer cell survival and colony growth in vitro, and on tumor growth in vivo, alone and in combination with Frondoside-A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, and camptothecin.

Results

We demonstrate that butein causes a concentration- and time-dependent decrease in the viability of the lung cancer cells (A549 and LNM35), the breast cancer cells (MDA-MB-231 and T47D), and a decrease in their related colonies growth in vitro. Similarly, treatment with butein significantly decreased the growth of A549 and MDA-MB-231 xenografts in the chick embryo model in vivo (P < 0.01) without significant toxicity. To determine whether the inhibition of cell viability and tumor growth by butein is due to growth arrest or to cell death, we assessed the induction of apoptosis by measuring caspase-3 activity and PARP cleavage. The treatment of lung and breast cancer cells with butein induce caspase-3 activation leading to PARP inactivation in a concentration and time-dependent manner. More than 50% of lung cancers and 40% of breast cancers show constitutive activation of STAT3. The role of this transcription factor in cancer progression is now well established and its targeting in cancer therapy is a very promising and challenging option. We observed that butein treatment induce a concentration and time-dependent inhibition of STAT3 phosphorylation without any impact on total STAT3. We finally demonstrate that butein at the IC25 and IC50 concentration enhances the anti-cancer effect of Frondoside-A as well as the effect of camptothecin on lung and breast cancer cells in vitro.

Conclusions

These findings increase our confidence of the potential benefit of using butein as an anticancer agent for the treatment of solid tumors either alone, and/or in combination with Frondoside-A and camptothecin.

Legal entity responsible for the study

Samir Attoub.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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