# Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-κB/MMP-9 Pathway

**Authors:** Chun-Tang Chiu, Jing-Hsien Chen, Fen-Pi Chou, Hui-Hsuan Lin

PMC · DOI: 10.3390/nu7075065 · Nutrients · 2015-06-24

## TL;DR

This study shows that Hibiscus sabdariffa leaf extract reduces prostate cancer cell invasion by blocking a specific signaling pathway.

## Contribution

The study identifies a novel mechanism by which HLE inhibits cancer cell invasion via the Akt/NF-κB/MMP-9 pathway.

## Key findings

- HLE inhibits migration and invasion of LNCaP prostate cancer cells.
- HLE suppresses MMP-9 activity and expression through NF-κB inactivation.
- HLE inhibits cancer cell growth and metastasis-related proteins in vivo.

## Abstract

Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-κB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-κB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.

## Linked entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318]
- **Proteins:** AKT1 (AKT serine/threonine kinase 1), NFKB1 (nuclear factor kappa B subunit 1)
- **Diseases:** prostate cancer (MONDO:0005159)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** NUCLEOLIN (nucleolin multifunctional protein) [NCBI Gene 4691] {aka C23, NCL, Nsr1}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}
- **Diseases:** Tumor (MESH:D009369), hyperglycemia (MESH:D006943), Prostate Cancer (MESH:D011471), lymph node carcinoma of the prostate (MESH:D011472), cytotoxicity (MESH:D064420), hypertension (MESH:D006973), diabetic (MESH:D003920), pyrexia (MESH:D005334), gastric carcinoma (MESH:D013274), CaP (MESH:C579969), leukemia (MESH:D007938), atherosclerosis (MESH:D050197), liver disorders (MESH:D017093), hypoglycemic (MESH:C000721848), male-specific malignancy (MESH:D005834), CaP metastasis (MESH:D009362), carcinogenesis (MESH:D063646),  (MESH:D009361),  (MESH:D002277)
- **Chemicals:** AlCl3 6H2O (-), (-)-epigallocatechin (MESH:C057580), curcumin (MESH:D003474), GA (MESH:D005708), formic acid (MESH:C030544), (-)-epicatechin gallate (MESH:C062669), polyphenol (MESH:D059808), protocatechuic acid (MESH:C009091), Giemsa (MESH:D001399), poly (dI dC) (MESH:C031156), PBS (MESH:D007854), acetic acid (MESH:D019342), water (MESH:D014867), guanidinium chloride (MESH:D019791), gossypin (MESH:C022944), oligonucleotide (MESH:D009841), formazan (MESH:D005562), Triton X-100 (MESH:D017830), KCl (MESH:D011189), acrylamide (MESH:D020106), CaCl2 (MESH:D002122), EA (MESH:D004976), nylon (MESH:D009757), aflatoxin (MESH:D000348), methanol (MESH:D000432), NaN3 (MESH:D019810), SDS (MESH:D012967), ferulic acid (MESH:C004999), isopropanol (MESH:D019840), glutamine (MESH:D005973), naringenin (MESH:C005273), DTT (MESH:D004229), Folin-Ciocalteau reagent (MESH:C029556), NaOH (MESH:D012972), lipid (MESH:D008055), streptomycin (MESH:D013307), polyacrylamide (MESH:C016679), CO2 (MESH:D002245), ethanol (MESH:D000431), NaNO2 (MESH:D012977), FA (MESH:D005492), MgCl2 (MESH:D015636), biotin (MESH:D001710), flavonoid (MESH:D005419), Lipofectamine (MESH:C086724), acetonitrile (MESH:C032159), gallic acid (MESH:D005707), Catechin (MESH:D002392), Ellagic acid (MESH:D004610), Na2CO3 (MESH:C005686), quercetin (MESH:D011794), bis-acrylamide (MESH:C021221), penicillin (MESH:D010406), rutin (MESH:D012431), anthocyanin (MESH:D000872), metformin (MESH:D008687), MTT (MESH:C070243), gossypetin (MESH:C059922), agarose (MESH:D012685), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616)
- **Species:** Homo sapiens (human, species) [taxon 9606], Hibiscus sabdariffa (red-sorrel, species) [taxon 183260], Haplochromis sp. LE (species) [taxon 1202858], Rhizopus stolonifer (species) [taxon 4846], Mus musculus (house mouse, species) [taxon 10090], Aspergillus fumigatus (species) [taxon 746128], Trichophyton mentagrophytes (species) [taxon 523103]
- **Cell lines:** LNCaP — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0395), HLE — Homo sapiens (Human), Transformed cell line (CVCL_F544)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4516987/full.md

## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC4516987/full.md

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Source: https://tomesphere.com/paper/PMC4516987