Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma

Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown tha...

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Main Authors: Kalaivani Buskaran, Saifullah Bullo, Mohd Zobir Hussein, Mas Jaffri Masarudin, Mohamad Aris Mohd Moklas, Sharida Fakurazi
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Materials
Subjects:
Online Access:https://www.mdpi.com/1996-1944/14/4/817
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author Kalaivani Buskaran
Saifullah Bullo
Mohd Zobir Hussein
Mas Jaffri Masarudin
Mohamad Aris Mohd Moklas
Sharida Fakurazi
author_facet Kalaivani Buskaran
Saifullah Bullo
Mohd Zobir Hussein
Mas Jaffri Masarudin
Mohamad Aris Mohd Moklas
Sharida Fakurazi
author_sort Kalaivani Buskaran
collection DOAJ
description Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites’ physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP–PCA–FA) in HepG2 cells. In conclusion, GOP–PCA–FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP–PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.
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spelling doaj.art-aa1e493e15114cb0a22eca67e5294b2f2023-12-03T12:57:15ZengMDPI AGMaterials1996-19442021-02-0114481710.3390/ma14040817Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular CarcinomaKalaivani Buskaran0Saifullah Bullo1Mohd Zobir Hussein2Mas Jaffri Masarudin3Mohamad Aris Mohd Moklas4Sharida Fakurazi5Laboratory for Vaccine and Immunotherapeutic, Institute of Biosciences, Universiti Putra Malaysia, Serdang, Selangor 43400, MalaysiaMaterials Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor 43400, MalaysiaMaterials Synthesis and Characterization Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor 43400, MalaysiaDepartment of Cell and Molecular Biology, School of Biotechnology, Universiti Putra Malaysia, Serdang, Selangor 43400, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, MalaysiaLaboratory for Vaccine and Immunotherapeutic, Institute of Biosciences, Universiti Putra Malaysia, Serdang, Selangor 43400, MalaysiaLiver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites’ physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP–PCA–FA) in HepG2 cells. In conclusion, GOP–PCA–FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP–PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.https://www.mdpi.com/1996-1944/14/4/817graphene oxideprotocatechuic acidnanocompositedrug deliveryfolic acid targetinganticancer mechanism
spellingShingle Kalaivani Buskaran
Saifullah Bullo
Mohd Zobir Hussein
Mas Jaffri Masarudin
Mohamad Aris Mohd Moklas
Sharida Fakurazi
Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
Materials
graphene oxide
protocatechuic acid
nanocomposite
drug delivery
folic acid targeting
anticancer mechanism
title Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
title_full Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
title_fullStr Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
title_full_unstemmed Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
title_short Anticancer Molecular Mechanism of Protocatechuic Acid Loaded on Folate Coated Functionalized Graphene Oxide Nanocomposite Delivery System in Human Hepatocellular Carcinoma
title_sort anticancer molecular mechanism of protocatechuic acid loaded on folate coated functionalized graphene oxide nanocomposite delivery system in human hepatocellular carcinoma
topic graphene oxide
protocatechuic acid
nanocomposite
drug delivery
folic acid targeting
anticancer mechanism
url https://www.mdpi.com/1996-1944/14/4/817
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