Anticancer Effect of Marine Sponge-Associated Bacillus pumilus AMK1 Derived Dipeptide Cyclo (-Pro-Tyr) in Human Liver Cancer Cell Line Through Apoptosis and G2/M Phase Arrest

Karanam, Gayathri; Arumugam, Madan Kumar; Natesh, Nagabhishek Sirpu

doi:10.1007/s10989-019-09850-2

Cited by 18 publications

(15 citation statements)

References 50 publications

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“…This is in congruence with our current findings where no toxicity of maculosin was observed in the BSLA until the test concentration of 128 mg/mL. However, available literature indicated that maculosin showed cytotoxic activity (IC 50 , 48.90 mg/mL) against the human liver cancer cell lines (Karanam et al 2020). Such observations indicated that maculosin's cytotoxic activity is selective against the liver cancer cell line.…”

Section: Discussionsupporting

confidence: 92%

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Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

Paudel

Maharjan

Rajbhandari

et al. 2021

Pharmaceutical Biology

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Context: Streptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities.Objective: This study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed. Materials and methods: The compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay. Results: Ethyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 mg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12-KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C 14 H 16 N 2 O 3 as determined by the [M þ H] þ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC 50 , 2.16 ± 0.05 mg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC 50 , 4.8 ± 0.05 mg/mL). No toxicity was observed for maculosin (LD 50 , <128 mg/mL) in brine shrimp lethality assay (BSLA) up to the compound's antioxidant activity (IC 50 ) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD 50 value of 8.63 ± 0.15 mg/mL. Conclusions: Maculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.

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Section: Discussionsupporting

confidence: 92%

“…However, available literature indicated that maculosin showed cytotoxic activity (IC 50 , 48.90 µg/mL) against the human liver cancer cell lines (Karanam et al. 2020 ). Such observations indicated that maculosin’s cytotoxic activity is selective against the liver cancer cell line.…”

Section: Discussionmentioning

confidence: 99%

Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

Paudel

Maharjan

Rajbhandari

et al. 2021

Pharmaceutical Biology

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“…associated with Callyspongia sp. [ 38 ] and the dipeptide cyclo(-Pro-Tyr) produced by Bacillus pumilus associated with Callyspongia fistularis [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria

et al. 2021

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Marine sponges harbor diverse microbial communities that represent a significant source of natural products. In the present study, extracts of 21 sponge-associated bacteria were screened for their antimicrobial and anticancer activity, and their genomes were mined for secondary metabolite biosynthetic gene clusters (BGCs). Phylogenetic analysis assigned the strains to four major phyla in the sponge microbiome, namely Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes. Bioassays identified one extract with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity, and more than 70% of the total extracts had a moderate to high cytotoxicity. The most active extracts were derived from the Proteobacteria and Actinobacteria, prominent for producing bioactive substances. The strong bioactivity potential of the aforementioned strains was also evident in the abundance of BGCs, which encoded mainly beta-lactones, bacteriocins, non-ribosomal peptide synthetases (NRPS), terpenes, and siderophores. Gene-trait matching was performed for the most active strains, aiming at linking their biosynthetic potential with the experimental results. Genetic associations were established for the anti-MRSA and cytotoxic phenotypes based on the similarity of the detected BGCs with BGCs encoding natural products with known bioactivity. Overall, our study highlights the significance of combining in vitro and in silico approaches in the search of novel natural products of pharmaceutical interest.

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“…Another study showed that a CDP mix composed of cyclo-(L-Pro-L-Tyr), cyclo-(L-Pro-L-Val), and cyclo-(L-Pro-L-Phe), isolated from the P. aeruginosa PAO1 strain, exhibited anticancer activity in HeLa and Caco-2 cell lines 66 . In another study cyclo-(-Pro-Tyr) exhibited anticancer and anti-proliferative activity against HepG2 cell lines 67 . A previous study has proven the anticancer activity of 1, 2-Benzenedicarboxylic acid, bis (2-ethylhexyl) ester on PC3, MCF, HCT-116, A549, and MIAPACA cell lines 68 .…”

Section: Discussionmentioning

confidence: 94%

A newly isolated strain of Halomonas sp. (HA1) exerts anticancer potential via induction of apoptosis and G2/M arrest in hepatocellular carcinoma (HepG2) cell line

El-Garawani

El-Sabbagh

Abbas

et al. 2020

Sci Rep

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Marine bacterial strains are of great interest for their ability to produce secondary metabolites with anticancer potentials. Isolation, identification, characterization and anticancer activities of isolated bacteria from El-Hamra Lake, Wadi El-Natrun (Egypt) were the objectives of this study. The isolated bacteria were identified as a moderately halophilic alkaliphilic strain. Ethyl acetate extraction was performed and identified by liquid chromatography-mass spectrophotometry (LC-MS-MS) and nuclear magnetic resonance analysis (NMR). Cytotoxicity of the extract was assessed on the HepG2 cell line and normal human peripheral lymphocytes (HPBL) in vitro. Halomonas sp. HA1 extract analyses revealed anticancer potential. Many compounds have been identified including cyclo-(Leu-Leu), cyclo-(Pro-Phe), C17-sphinganine, hexanedioic acid, bis (2-ethylhexyl) ester, surfactin C14 and C15. The extract exhibited an IC 50 of 68 ± 1.8 μg/mL and caused marked morphological changes in treated HepG2 cells. For mechanistic anticancer evaluation, 20 and 40 µg/mL of bacterial extract were examined. The up-regulation of apoptosis-related genes' expression, P53, CASP-3, and BAX/ BCL-2 at mRNA and protein levels proved the involvement of P53-dependant mitochondrial apoptotic pathway. The anti-proliferative properties were confirmed by significant G 2 /M cell cycle arrest and PCNA down-regulation in the treated cells. Low cytotoxicity was observed in HPBL compared to HepG2 cells. In conclusion, results suggest that the apoptotic and anti-proliferative effects of Halomonas sp. HA1 extract on HepG2 cells can provide it as a candidate for future pharmaceutical industries. Abbreviations NMR Nuclear magnetic resonance LC-MS-MS Liquid chromatography-mass spectrophotometry MeOH Methanol DMSO Dimethyl sulphoxide

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Anticancer Effect of Marine Sponge-Associated Bacillus pumilus AMK1 Derived Dipeptide Cyclo (-Pro-Tyr) in Human Liver Cancer Cell Line Through Apoptosis and G2/M Phase Arrest

Cited by 18 publications

References 50 publications

Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18

Bioactivity Screening and Gene-Trait Matching across Marine Sponge-Associated Bacteria

A newly isolated strain of Halomonas sp. (HA1) exerts anticancer potential via induction of apoptosis and G2/M arrest in hepatocellular carcinoma (HepG2) cell line

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