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The Antiproliferative and Apoptosis-Inducing Effects of the Red Macroalgae Gelidium latifolium Extract against Melanoma Cells.

ABSTRACT: The red macroalga Gelidium latifolium is widely distributed in the coastal areas of Indonesia. However, current knowledge on its potential biological activities is still limited. In this study, we investigated the potential bioactive compounds in Gelidium latifolium ethanol extract (GLE), and its cytotoxic effects against the murine B16-F10 melanoma cell line. GLE shows high total phenolic content (107.06 ± 17.42 mg GAE/g) and total flavonoid content (151.77 ± 3.45 mg QE/g), which potentially contribute to its potential antioxidant activity (DPPH = 650.42 ± 2.01 µg/mL; ABTS = 557.01 ± 1.94 µg/mL). ESI-HR-TOF-MS analysis revealed large absorption in the [M-H]^- of 327.2339 m/z, corresponding to the monoisotopic molecular mass of brassicolene. The presence of this compound potentially contributes to GLE's cytotoxic activity (IC₅₀ = 84.29 ± 1.93 µg/mL). Furthermore, GLE significantly increased the number of apoptotic cells (66.83 ± 3.06%) compared to controls (18.83 ± 3.76%). Apoptosis was also confirmed by changes in the expression levels of apoptosis-related genes (i.e., p53, Bax, Bak, and Bcl2). Downregulated expression of Bcl2 indicates an intrinsic apoptotic pathway. Current results suggest that components of Gelidium latifolium should be further investigated as possible sources of novel antitumor drugs.

SUBMITTER: Prasedya ES

PROVIDER: S-EPMC8587204 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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The Antiproliferative and Apoptosis-Inducing Effects of the Red Macroalgae Gelidium latifolium Extract against Melanoma Cells.

Prasedya Eka Sunarwidhi ES Ardiana Nur N Padmi Hasriaton H Ilhami Bq Tri Khairina BTK Martyasari Ni Wayan Riyani NWR Sunarwidhi Anggit Listyacahyani AL Nikmatullah Aluh A Widyastuti Sri S Sunarpi Haji H Frediansyah Andri A

Molecules (Basel, Switzerland) 20211030 21

The red macroalga Gelidium latifolium is widely distributed in the coastal areas of Indonesia. However, current knowledge on its potential biological activities is still limited. In this study, we investigated the potential bioactive compounds in Gelidium latifolium ethanol extract (GLE), and its cytotoxic effects against the murine B16-F10 melanoma cell line. GLE shows high total phenolic content (107.06 ± 17.42 mg GAE/g) and total flavonoid content (151.77 ± 3.45 mg QE/g), which ...[more]

PMID: 34770978

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Project description:BackgroundCrinum latifolium L. (Amaryllidaceae) has been used in Southeast Asian traditional medicine to alleviate the symptoms of benign prostatic hyperplasia (BPH). The pathological mechanism of BPH is associated with the induction of prostate stromal cell proliferation through transforming growth factor-beta (TGF-β). Standardization as well as investigation of the potential anti-BPH activity of C. latifolium extract could benefit the further development of BPH-related analyses and provide evidence to support the application of this extract for BPH treatment. This study aimed to standardize and investigate the antiproliferative activity of the ethanolic extract of C. latifolium leaves. The major alkaloids isolated from C. latifolium were also explored for their potential use as bioactive markers.MethodsTwo major alkaloids were isolated from the ethanolic extract of C. latifolium leaves by chromatographic techniques, identified by NMR and MS, and quantified by a validated UHPLC method. Their antiproliferative activity was studied in human prostate stromal cells (WPMY-1) induced by TGF-β. The synergistic effect of combining the two major isolated alkaloids was analyzed by the zero interaction potency (ZIP) model.ResultsTwo alkaloids, lycorine (1) and 6α-hydroxybuphanidrine (2), were isolated from the ethanolic leaf extract of C. latifolium. A UHPLC method for the quantification of (1) and (2) was developed and validated in terms of linearity, precision, and accuracy. The C. latifolium leaf extract contained 0.279 ± 0.003% (1) and 0.232 ± 0.004% (2). The crude extract was more potent than either (1) and (2) alone against TGF-β-treated WPMY-1 cell proliferation. The drug combination study revealed that the greatest synergistic effect of (1) and (2) was achieved at a 1:1 ratio.ConclusionsThe results of this study support the anti-BPH activity of C. latifolium in traditional medicine and suggest that these the two isolated alkaloids may promote the efficacy of the C. latifolium extract. Additionally, major alkaloids (1) and (2) can be used as bioactive markers for the standardization of C. latifolium extracts.

Project description:: Cassia fistula L. is a highly admirable traditional medicinal plant used for the treatment of various diseases and disorders. The present study was performed to divulge the antioxidant, antiproliferative, and apoptosis-inducing efficacy of fractions from C. fistula leaves. The hexane (CaLH fraction), chloroform (CaLC fraction), ethyl acetate (CaLE fraction), n-butanol (CaLB fraction), and aqueous (CaLA fraction) were sequentially fractionated from 80% methanolic (CaLM extract) of C. fistula leaves. The CaLE fraction was fractionated using column chromatography to yield a pure compound, which was characterized as Epiafzelechin (CFL1) based on 1H, 13C, and DEPT135 NMR. Among these fractions, CaLE and isolated CFL1 fractions exhibited an effective antioxidant potential in Ferric ion reducing power, (2,2'-azino-bis (3-ethylbenzothiazoline -6-sulfonic acid)) cation radical scavenging, and nitric oxide radical scavenging assays. Epiafzelechin was investigated for its antiproliferative effects against MG-63 (osteosarcoma), IMR-32 (neuroblastoma), and PC-3 (prostate adenocarcinoma), and was found to inhibit cell proliferation with a GI50 value of 8.73, 9.15, and 11.8 ?M respectively. MG-63 cells underwent apoptotic cell death on treatment with Epiafzelechin as the cells showed the formation of apoptotic bodies, enhanced reactive oxygen species (ROS) generation, mitochondrial membrane depolarization along with an increase in early apoptotic cell population analyzed using Annexin V-FITC/PI double staining assay. Cells showed cell cycle arrest at the G0/G1 phase accompanied by a downregulation in the expression levels of p-Akt (Protein kinase B), p-GSK-3? (Glycogen synthase kinase-3 beta), and Bcl-xl (B-cell lymphoma-extra large) proteins. RT-PCR (Real time-polymerase chain reaction) analysis revealed downregulation in the gene expression level of ?-catenin and CDK2 (cyclin-dependent kinases-2) while it upregulated the expression level of caspase-8 and p53 genes in MG-63 cells.

Dataset Information

The Antiproliferative and Apoptosis-Inducing Effects of the Red Macroalgae Gelidium latifolium Extract against Melanoma Cells.

Publications

The Antiproliferative and Apoptosis-Inducing Effects of the Red Macroalgae <i>Gelidium latifolium</i> Extract against Melanoma Cells.

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