Growth Inhibition and Apoptotic Effect of Pine Extract and Abietic Acid on MCF-7 Breast Cancer Cells via Alteration of Multiple Gene Expressions Using In Vitro Approach.

Hesham Haffez,Hassan Y Ebrahim,Zeinab A Hassan,Shimaa Osman

doi:10.3390/molecules27010293

Abstract

In vitro anti-proliferative activity of Pinus palustris extract and its purified abietic acid was assessed against different human cancer cell lines (HepG-2, MCF-7 and HCT-116) compared to normal WI-38 cell line. Abietic acid showed more promising IC50 values against MCF-7 cells than pine extract (0.06 µg/mL and 0.11 µM, respectively), with insignificant cytotoxicity toward normal fibroblast WI-38 cells. Abietic acid triggered both G2/M cell arrest and subG0-G1 subpopulation in MCF-7, compared to SubG0-G1 subpopulation arrest only for the extract. It also induced overexpression of key apoptotic genes (Fas, FasL, Casp3, Casp8, Cyt-C and Bax) and downregulation of both proliferation (VEGF, IGFR1, TGF-β) and oncogenic (C-myc and NF-κB) genes. Additionally, abietic acid induced overexpression of cytochrome-C protein. Furthermore, it increased levels of total antioxidants to diminish carcinogenesis and chemotherapy resistance. P. palustris is a valuable source of active abietic acid, an antiproliferative agent to MCF-7 cells through induction of apoptosis with promising future anticancer agency in breast cancer therapy.

Highlights

IntroductionIn the anticancer drug discovery pipeline, natural products are one of the most robust starting points for initiating the development of anticancer therapeutics
MTT assay was used to assess the antiproliferative activity of both pine extract and its pure abietic acid active compound against three different cancer cell lines
We found that abietic acid showed dose-dependent growth inhibitory effects on the MF-7 cells

Summary

Introduction

In the anticancer drug discovery pipeline, natural products are one of the most robust starting points for initiating the development of anticancer therapeutics. This was demonstrated by the remarkable clinical successes of paclitaxel, doxorubicin, vincristine, vinblastine, and many other eminent examples [2]. Natural product-derived anticancer agents have the advantage of being less toxic to normal cells than malignant ones. This should surely provide some impetus to uncover the biological effects of natural products and study their interactions with cancerous cells at the molecular level in order to better understand cancer biology and hypothesize rational strategies for controlling cancers

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Conclusion