DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria

Antony, Jayesh; Saikia, Minakshi; Vinod,; Nath, Lekshmi R; Katiki, Mohana Rao; Murty, M. S. R.; Paul, Anju K; Shabna, Anwar; Chandran, Harsha; Joseph, Sophia Margaret; S, Nishanth Kumar; Panakkal, Elizabeth Jayex; Sriramya, I; Sridivya, I; Ran, Sophia; Sambandam, Sankar; Rajan, Easwary; Anto, Ruby John

doi:10.1038/srep11107

Cited by 22 publications

(12 citation statements)

References 37 publications

(48 reference statements)

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“…Nuclear extracts of the cells treated with or without the compound were prepared and EMSA was conducted to evaluate DNA-binding activity of NF-κ B as described earlier2729 (SI methods).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

Nath

Gorantla

Thulasidasan

et al. 2016

Sci Rep

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We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib (IC50: 5.8 μM), the only FDA-approved drug for liver cancer. Moreover, it induces cytotoxicity in all liver cancer cell lines, irrespective of their HBV status, while being non-toxic to normal immortalized hepatocytes. It induces apoptosis in HepG2 cells by down-regulating mainly the activation of MAPK and mTOR pathways. The drastic reduction in HepG2-xenograft tumor size achieved by uttroside B in NOD-SCID mice and substantiation of its biological safety through both acute and chronic toxicity studies in Swiss albino mice warrants clinical validation of the molecule against hepatic cancer, for which, the chemotherapeutic armamentarium currently has limited weapons.

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“…Nuclear extracts of the cells treated with or without the compound were prepared and EMSA was conducted to evaluate DNA-binding activity of NF-κ B as described earlier2729 (SI methods).…”

Section: Methodsmentioning

confidence: 99%

Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

Nath

Gorantla

Thulasidasan

et al. 2016

Sci Rep

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“…Nuclear accumulation of β-catenin, a key regulator of Wnt path way is found to be important in melanoma progression ( Widlund et al, 2002 ; Chien et al, 2009 ). A recent report from our lab has shown that a fraction, DW-F5 isolated from Wrightia tinctoria inhibits the proliferation and progression of melanoma tumor by down-regulating the pivotal molecules such as Brn-2, β-catenin and BRAF along with MITF-M, the master regulator of melanocyte development ( Antony et al, 2015 ). It was very interesting to note that DETS also strongly down-regulate the expression of β-catenin revealing the efficacy of this compound in regulating Wnt signaling.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-ethyl-trans-stilbene (DETS) Isolated from Bacillus cereus as a Potent Candidate against Malignant Melanoma

et al. 2016

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3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 μM] followed by cervical [HeLa-46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS in A375 cells (IC50-24.01 μM), with that in SK-MEL-2 (IC50-67.6 μM), another melanoma cells which highly over-express MITF-M. The compound arrests the cells at S-G2 transition state of the cell cycle, as resveratrol. Our results indicate that DETS is a powerful antioxidant, having anticancer efficacy comparable with that of resveratrol, and is a potential candidate to be explored by in vivo studies and in-depth mechanistic evaluation. To our knowledge, this is the first report on the antioxidant and anticancer properties of DETS.

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“…The viability of cells upon treatment with heteronemin and/or cytarabine was determined by MTT assay as described earlier [ 42 ] and the relative cell viability percentage is expressed as (Abs 570 of treated wells/Abs 570 of untreated wells) × 100.…”

Section: Methodsmentioning

confidence: 99%

Heteronemin, a marine natural product, sensitizes acute myeloid leukemia cells towards cytarabine chemotherapy by regulating farnesylation of Ras

et al. 2018

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Cytarabine is a conventionally used chemotherapeutic agent for treating acute myeloid leukemia (AML). However, chemoresistance, toxic side-effects and poor patient survival rates retard the efficacy of its performance. The current study deals with the chemosensitization of AML cells using heteronemin, a marine natural product towards cytarabine chemotherapy. Heteronemin could effectively sensitize HL-60 cells towards sub-toxic concentration of cytarabine resulting in synergistic toxicity as demonstrated by MTT assay and [3H] thymidine incorporation studies, while being safe towards healthy blood cells. Flow cytometry for Annexin-V/PI and immunoblotting for caspase cleavage proved that the combination induces enhancement in apoptosis. Heteronemin being a farnesyl transferase inhibitor (FTI) suppressed cytarabine-induced, farnesyl transferase-mediated activation of Ras, as assessed by Ras pull-down assay. Upon pre-treating cells with a commercial FTI, L-744,832, the synergism was completely lost in the combination, confirming the farnesyl transferase inhibitory activity of heteronemin as assessed by thymidine incorporation assay. Heteronemin effectively down-regulated cytarabine-induced activation of MAPK, AP-1, NF-κB and c-myc, the down-stream targets of Ras signaling, which again validated the role of Ras in regulating the synergism. Hence we believe that the efficacy of cytarabine chemotherapy can be improved to a significant extent by combining sub-toxic concentrations of cytarabine and heteronemin.

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DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria

Cited by 22 publications

References 37 publications

Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-ethyl-trans-stilbene (DETS) Isolated from Bacillus cereus as a Potent Candidate against Malignant Melanoma

Heteronemin, a marine natural product, sensitizes acute myeloid leukemia cells towards cytarabine chemotherapy by regulating farnesylation of Ras

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