Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways

Su Chern Foo; Fatimah Md Yusoff; Mustapha Umar Imam; Jhi Biau Foo; Norsharina Ismail; Nur Hanisah Azmi; Yin Sim Tor; Nicholas M H Khong; Maznah Ismail

doi:10.1016/j.btre.2018.e00296

Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways

Biotechnol Rep (Amst). 2018 Dec 6:21:e00296. doi: 10.1016/j.btre.2018.e00296. eCollection 2019 Mar.

Authors

Su Chern Foo^{1

2}, Fatimah Md Yusoff^{1

3

4}, Mustapha Umar Imam^{1

5}, Jhi Biau Foo^{1

6}, Norsharina Ismail¹, Nur Hanisah Azmi^{1

7}, Yin Sim Tor^{1

8}, Nicholas M H Khong¹, Maznah Ismail¹

Affiliations

¹ Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.
² School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
³ The International Institute of Aquaculture and Aquatic Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor Darul Ehsan, Malaysia.
⁴ Department of Aquaculture, Faculty of Agriculture, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.
⁵ Department of Medical Biochemistry, College of Health Sciences, Usmanu Danfodio University, Sokoto, Nigeria.
⁶ School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, No. 1 Jalan Taylor's, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia.
⁷ Department of Cell and Molecular Biology, Faculty of Biotechnology & Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
⁸ School of Biosciences, Faculty of Health & Medical Sciences, Taylor's University, No. 1 Jalan Taylor's, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia.

Abstract

In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC₅₀: 18.89 μg.mL^-1) was found to be significantly more potent than CME (IC₅₀: 87.5 μg.mL^-1) (p < 0.05). Gene expression studies revealed that anti-proliferative effects in treated cells by C. calcitrans extracts were mediated partly through the modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, JNK), apoptosis (BAX, BID, Bcl-2, APAF, CYCS) and oxidative stress (SOD1, SOD2, CAT). Overall, C. calcitrans extracts demonstrated effective intervention against HepG2 cancer cells where enhanced apoptotic activities were observed with increased fucoxanthin content.

Keywords: Apoptosis; CME, crude methanolic extract; Chaetoceros calcitrans; DMSO, dimethyl sulfoxide; Fucoxanthin; FxRF, fucoxanthin rich fraction; Gene expression; MTT, 3-(4,5-dimethylthizol-2-yl-2,5 diphenyltetrazolium bromide); Microalgae; PBS, phosphate buffered saline; RNA, ribonucleic acid; Rich fraction; mg FX.g−1 extract, milligram of fucoxanthin per gram of Chaetoceros calcitrans extract.