Systemic Evaluation of Mechanism of Cytotoxicity in Human Colon Cancer HCT-116 Cells of Silver Nanoparticles Synthesized Using Marine Algae Ulva lactuca Extract

Diptikanta Acharya,Kanti Kusum Yadav,Sagarika Satapathy,Prathap Somu,Gitanjali Mishra

doi:10.1007/s10904-021-02133-8

Abstract

In the current study, biogenic silver nanoparticles (U-AgNPs) were synthesized using marine green macro-algal Ulva lactuca extract, and evaluated mechanism behind its anticancer activity against the Human colon cancer (HCT-116). The biogenic U-AgNPs were characterized using various physiochemical techniques. The TEM micrographs confirmed the spherical morphology of synthesized U-AgNPs, with a mean size of 8–14 nm. EDX spectrum as well as ICP-OES confirmed that AgNPs was nearly 90% purity for silver. FTIR Spectra analysis of U-AgNPs confirmed U. lactuca extract bioactive molecules presence over U-AgNPs surface as a stabilizing agent, thereby improving biocompatibility. The cytotoxicity study revealed the dose dependent cell death in colon cancer cells with no loss of viability in normal human colon epithelial cells. Furthermore, the fluorescence micrographs of nucleus staining assay revealed the DNA fragmentation and nucleus condensation of cancer cells treated with U-AgNPs, indicating an apoptosis-mediated cell death. The western bolt and RT-PCR analysis of U-AgNPs treated cancer cells showed the rise in proapoptotic markers (P53, Bax, and P21) and decline in anti-apoptotic markers (Bcl-2), thus confirming the p53-dependent apoptosis mediated cell death in HCT-116. Overall, our study concluded that novel biogenic U-AgNPs nanoparticles, synthesized using marine green macro-algal U. lactuca extract showed efficient anticancer activity against HCT-116 cell line and hence could work as potential therapeutic agent for targeted anti-cancer therapy.

Highlights

Colorectal cancer is fourth among cancer-related deaths and the third commonly occurring malignancy amounting to up to 9.7% of all cancers as per the report of the International Agency for Research [1]
Metal nanoparticles have like silver nanoparticles (AgNPs) have distinctive properties comparatively whose exploitation has led to the breakthrough in various domains such as biomedical diagnostics [8], food industry [9], therapeutic agent [10, 11], drug delivery [12], and antimicrobial agent [13,14,15]
To confirm the apoptosis mediated cell death by U-AgNPs in the cancer cell, we examined the mRNA levels of apoptosis markers in HCT-116 cells after treatment with U-AgNPs where anti-apoptotic (Bcl-2) as well as pro-apoptotic markers (P53, Bax, and P21) were determined against glyceraldehyde-3- phosphate dehydrogenase (GAPDH) as control (Fig. 8)

Summary

Introduction

Colorectal cancer is fourth among cancer-related deaths and the third commonly occurring malignancy amounting to up to 9.7% of all cancers as per the report of the International Agency for Research [1]. Reports have projected that colorectal cancer will spike up to 2.4 million by 2035. The conventional method of the treatment of colorectal cancer is chemotherapy mainly employing fluoropyrimidine 5fluorouracil but suffers greatly by poor prognosis due to the side effects of chemotherapy and multi-drug resistance (MDR) as a consequence of low solubility and improper drug distribution [2, 3]. Metal nanoparticles have like silver nanoparticles (AgNPs) have distinctive properties comparatively whose exploitation has led to the breakthrough in various domains such as biomedical diagnostics [8], food industry [9], therapeutic agent [10, 11], drug delivery [12], and antimicrobial agent [13,14,15]

Methods

Results

Conclusion