Nanonutraceuticals: Anti-Cancer Activity and Improved Safety of Chemotherapy by Costunolide and Its Nanoformulation against Colon and Breast Cancer.

Ali El-Far,Taher Salaheldin,Kavitha Godugu,Noureldien Darwish,Amna Saddiq,Shaker Mousa

doi:10.3390/biomedicines9080990

Ali El-Far, Taher Salaheldin + Show 4 more

Open Access

https://doi.org/10.3390/biomedicines9080990

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Abstract

Costunolide (COS) is a sesquiterpene lactone with anticancer properties. The present study investigated the anticancer effects of COS against the human colon (HCT116) and breast (MDA-MB-231-Luc) cancer cell lines. Inhibition of cell lines viability and IC50 of COS were assessed via an MTT assay. Furthermore, the apoptotic rate was detected by assessment of Bcl2-associated X (Bax) and B-cell lymphoma 2 (Bcl2) protein levels by flow cytometry. Xenograft mice model of HCT116 and MDA-MB-231-Luc were carried out to determine the effect of COS and its nanoparticles (COS-NPs). The results demonstrated that COS inhibited the viability of HCT116 and MDA-MB-231-Luc cells, with a half maximal inhibitory concentration value (IC50) of 39.92 µM and 100.57 µM, respectively. COS significantly increased Bax and decreased Bcl2 levels in treated cells. COS and COS-NPs, in combination with doxorubicin (DOX), significantly decreased the tumor growth of HCT116 and MDA-MB-231-Luc implants in mice. Furthermore, oral administration of COS and COS-NPs significantly decreased the viable cells and increased necrotic/apoptotic cells of HCT116 and MDA-MB-231-Luc implants. Interestingly, both COS and COS-NPs protected the cardiac muscles against DOX’s cardiotoxicity. The current results indicated the promising anticancer and cardiac muscles protection of COS and COS-NPs when administered with chemotherapy.

Highlights

Cancer is the second leading cause of death in the United States and is a global public health issue [1]
Iscove’s modified Dulbecco’s medium (IMDM), fetal bovine serum (FBS), penicillin, streptomycin, and trypsin/ethylenediaminetetraacetic acid (EDTA) were purchased from Sigma-Aldrich
After preparation of COS-NPS, we characterize it by Z-average particle size and zeta

Summary

Introduction

Cancer is the second leading cause of death in the United States and is a global public health issue [1]. In the United States, colorectal cancer is the third most frequently diagnosed cancer in both men and women [2]. The growth of colorectal cancer is dominated by age, as well as genetic and environmental factors [3]. Breast cancer is the world’s most prevalent malignant disease [4]. Triple-negative breast cancer (TNBC) is one of the subtypes of breast cancer that, in recent years, has not been identified as the estrogen receptor, progesterone receptor, or human growth factor 2 [5]. TNBC has severe invasiveness, high malignancy, and short relapse-free survival, representing the critical role of early diagnosis and precise progression [6]

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