Dietary Fatty Acids from Leaves ofClerodendrum VolubileInduce Cell Cycle Arrest, Downregulate Matrix Metalloproteinase-9 Expression, and Modulate Redox Status in Human Breast Cancer

Abstract

The antiproliferative effect of the fatty acid components of Clerodendrum volubile leaves as well as its antioxidant effect on MCF-7 and MDA-MB-231 human breast cancer cell lines were investigated. Fatty acids extracted from C. volubile leaf oil were subjected to gas chromatography mass spectrometry (GCMS) analysis. The cells were cultured and treated with the fatty acids for 48 h, after which the antiproliferation effect was ascertained via MTT assay and cell viability analysis using BD fluorescence activated cells sorting (FACS) Calibur. Cell cycle was analyzed by flow cytometry on FACS Calibur. Western blotting was used in determining expression of proteins in the cell lines. The treated cell lines were assessed for reduced glutathione level, catalase, superoxide dismutase, and lipid peroxidation. The fatty acids significantly inhibited cell proliferation, arrested G0/G1 phase, downregulated the expression of MMP-9, and attenuated oxidative stress in of MCF-7 cell lines but had little or no effect on MDA-MB-231 cell lines. These results indicate the therapeutic potential of the fatty acids components of the leaves of C. volubile on human breast cancer, which may be explored further in drug development.

Suppressive Effects of Clerodendrum volubile P Beauv. [Labiatae] Methanolic Extract and Its Fractions on Type 2 Diabetes and Its Complications

“…We also correlated the antidiabetic potential of the ethyl acetate fraction to the immunomodulatory activity of isolated protocatechuic acid ( Erukainure et al, 2017a ). We have shown the ability of dietary fatty acids from the leaves to arrest proliferation in human breast cancer cells ( Erukainure et al, 2016b ). The ability of the leaves extracts to inhibit to α-amylase, α-glucosidase and angiotensin-1 converting enzyme has been reported recently ( Adefegha and Oboh, 2016 ).…”

Anticancer Activity Of Plant Genus Clerodendrum (Lamiaceae): A Review

“…Lima senyawa yang berhasil diidentifikasi dalam tanaman genus ini yaitu apigenin 7-glucoside, hispidulin, scutellarein-7-O-beta-D-glucuronate, acteoside dan verbascoside menunjukan interaksi dengan protein kanker melalui simulasi penambatan molekul dan berpotensi menimbulkan efek terapi (Gogoi et al 2017 Wang, Zhu, et al 2013;Wang, Xiong, et al 2013;Xu et al 2013 memiliki aktivitas antikanker dari tanaman genus Clerodendrum adalah pheophorbide-related compounds (purpurin 7 dimethyl ester, pheophorbide a, methyl (10S)-hydroxypheophorbide a) (Cheng et al 2001); asam lemak (asam oleat, asam oktadekanoat, asam n-heksadekanoat, dan 6-metil-2-heptanon) (Erukainure et al 2016); asam oleanolik dan clerodinin A (Sannigrahi et al 2012); abitane diterpenoid (trichotomone, trichotomone D, trichotomone F, uncinatone, mandarone E, teuvincenone E, dan trichotomone H) (Wang, Xiong, et al 2013;Wang, Zhu, et al 2013) dan dua senyawa steroid (Xu et al 2013). Mekanisme antikanker beberapa tanaman genus Clerodendrum melalui aktivitas fotositoksisitas (Nakamura et al 1996;Choi et al 2014;Cheng et al 2001), apoptosis, antiproliferatif dan anti-migrasi (Sun et al 2013;Chacko et al 2015).…”

“…Aktivitas apoptosis ditunjukan oleh peningkatan rasio bax/bcl-2 dan peningkatan ekspresi caspase 9 (Chacko et al 2015). Sedangkan aktivitas antiproliferasi melalui inaktivasi MMP-9 dan induksi cell cycle arrest (Erukainure et al 2016). Aktivitas antikanker juga ditunjukan melalui aktivitas antioksidan, modifikasi lipid peroksidasi, menghambat metabolisme karsinogen dan meningkatkan proses detoksifikasinya (Manoharan et al 2006;Renju et al 2007;Lakshmi & Bai 2016a).…”

“…Aktivitas antikanker ekstrak daun C. infortunatum diduga oleh asam oleanolik dan clerodinin A yang terkandung di dalamnya (Sannigrahi et al 2012). Erukainure et al (2016) mengisolasi asam lemak dari daun C. volubile dan dilaporkan memiliki aktivitas antikanker pada sel kanker payudara MCF-7, dengan sedikit atau tidak memiliki efek pada sel kanker payudara MDA-MB-231 dan sel normal CC1. Komponen asam lemak yang berhasil diisolasi terdiri atas asam oleat yang…”

“…Hasil analisis dengan fluorescence activated cells sorting (FACS), isolat asam lemak dapat menghambat proliferasi >90% sel MCF-7, yang bergantung pada peningkatan konsentrasi. Hasil analisis siklus sel dengan flow cytometry, penentuan ekspresi protein dengan western blotting, reduksi glutation (GSH), katalase, superoksida dismutase (SOD), dan lipid peroksidasi, Erukainure et al (2016) menyimpulkan bahwa aktivitas antiproliferasi asam lemak isolat daun C. volubile melalui mekanisme 1) penghambatan ekspresi MMP-9 melalui inaktivasi MMP-9 yang mengaktivasi siklus sel, 2) modulasi homeostatis redoks yang menginaktivasi ekspresi MMP-9 dan fase G0/G1 dari siklus sel dan 3) inaktivasi fase G0/G1 yang menginduksi cell cycle arrest.…”