In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells

Noraini Nordin, Swee Keong Yeap, Heshu Sulaiman Rahman, Nur Rizi Zamberi, Nadiah Abu, Nurul Elyani Mohamad, Chee Wun How, Mas Jaffri Masarudin, Rasedee Abdullah, Noorjahan Banu Alitheen

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Abstract

Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.

Original languageEnglish
Article number1614
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019
Externally publishedYes

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citral
Breast Neoplasms
Lipids
Apoptosis
Tumor Burden
In Vitro Techniques
Cell Cycle

ASJC Scopus subject areas

  • General

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In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells. / Nordin, Noraini; Yeap, Swee Keong; Rahman, Heshu Sulaiman; Zamberi, Nur Rizi; Abu, Nadiah; Mohamad, Nurul Elyani; How, Chee Wun; Masarudin, Mas Jaffri; Abdullah, Rasedee; Alitheen, Noorjahan Banu.

In: Scientific Reports, Vol. 9, No. 1, 1614, 01.12.2019.

Research output: Contribution to journalArticle

Nordin, N, Yeap, SK, Rahman, HS, Zamberi, NR, Abu, N, Mohamad, NE, How, CW, Masarudin, MJ, Abdullah, R & Alitheen, NB 2019, 'In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells', Scientific Reports, vol. 9, no. 1, 1614. https://doi.org/10.1038/s41598-018-38214-x
Nordin, Noraini ; Yeap, Swee Keong ; Rahman, Heshu Sulaiman ; Zamberi, Nur Rizi ; Abu, Nadiah ; Mohamad, Nurul Elyani ; How, Chee Wun ; Masarudin, Mas Jaffri ; Abdullah, Rasedee ; Alitheen, Noorjahan Banu. / In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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AU - Zamberi, Nur Rizi

AU - Abu, Nadiah

AU - Mohamad, Nurul Elyani

AU - How, Chee Wun

AU - Masarudin, Mas Jaffri

AU - Abdullah, Rasedee

AU - Alitheen, Noorjahan Banu

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AB - Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.

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