Browsing by Author "Adhikari, A."

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    Cytotoxic effect of a resorcinolic lipid isolated from Mangifera zeylanica in a human cancer cell panel
    (Institute of Chemistry Ceylon Adamantane House, Rajagiriya, Sri Lanka., 2020) Rathnayaka, Rajitha K.; Samarakoon, Sameera R.; Ediriweera, M. K.; Tennekoon, K. H.; Adhikari, A.; Gunasekara, Dinara S.
    Cancer remains a leading cause of death worldwide. Surgery, chemotherapy, radiotherapy, hormonal therapy and immunotherapy are considered as treatment options for cancer. Plants have played a vital role as a source of effective anti-cancer agents, and 60% of anti-cancer agents derived from natural sources. Mangifera zeylanica is a plant endemic to Sri Lanka and its bark has been use in traditional medicine to treat some cancers. Cytotoxic compounds such as quercetin, chatecin, mangiferin and bromomangiferic acids have been reported in the bark extracts previously. Cytotoxic effect of a resorcinolic lipid (RL) in estrogen receptor-positive breast cancer (MCF-7), triple-negative breast cancer (MDA-MB-231) and epithelial ovarian cancer (SKOV-3) cells has evaluated in a previous study conducted in our laboratory. This study was performed to evaluate cytotoxic effects of RL [5-((8Z, 11Z, 14Z)-hexatriaconta-8, 11, 14-trienyl) benzene-1, 3-diol], a compound isolated from hexane extract of the bark of M. zeylanica, in small cancer cell panel containing human hepatocellular carcinoma (HepG2), colorectal adenocarcinoma (Caco-2), malignant mucoepidermoid pluripotent carcinoma (NTERA-2), renal cell adenocarcinoma (ACHN), mucoepidermoid pulmonary carcinoma (NCI-H292), epidermoid carcinoma (A-431), endometrium adenocarcinoma (AN3CA) and triplenegative breast cancer cells (Hs578t) and normal embryonic kidney cells (HEK-293). Sulforhodamine B (SRB) assay was carried out to evaluate the cytotoxic effects of the RL on the cancer cell panel. Prior to the SRB assays, cancer cells were treated with RL at concentrations ranging from 1.5625 to 25μg/ mL and incubated for 48 h. Results of the SRB assay demonstrated that RL excreted a potent in vitro cytotoxicity on all cancer cell lines tested (IC50 in μg/mL; HepG2: 2.31, Caco-2: 1.59, AN3CA: 1.28, Hs578t: <1.00, NTERA-2: <1.00, ACHN: 1.42, NCI-H292: 2.84 and A-431: 1.63) with less cytotoxicity to normal embryonic kidney cells (HEK-293: 4.44). Ethidium bromide/ Acridine orange staining revealed morphological evidence of apoptosis (including chromatin condensation, nuclear fragmentation and changes in the size and shape) in cancer cells. Overall results of the current study provide preliminary evidence to prove that RL can be develop as a potential drug to treats several types of human cancers.
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    In silico identification and in vitro validation of alpha-hederin as a potent inhibitor of Wnt/β-catenin signaling pathway in breast cancer stem cells.
    (Springer-Verlag, GmbH, 2024) Saliu, T.P.; Seneviratne, N.N.; Faizan, M.; Rajagopalan, U.; Perera, D.C.; Adhikari, A.; Senathilake, K.S.; Galhena, P.B.; Tennekoon, K.H.; Samarakoon, S.R.
    Cancer stem cells (CSCs) play a vital role in metastasis, recurrence and chemoresistance in breast cancer. β-catenin, which is a frequently over activated protein in CSCs, binds to T-cell factor/lymphoid enhancer factor (Tcf/Lef) family transcription factors leading to ectopic expression of Wnt pathway responsive genes necessary for the maintenance and action of CSCs. With the aim of identifying a small molecules that can effectively eliminate CSCs, molecular docking studies were performed against the Tcf/Lef binding hotspot on β-catenin using a library of 100 natural or synthetic small molecules. Small molecule ligands giving docking energy better than - 7 kcal/mol were further investigated by binding interactions analysis and molecular dynamics (MD) simulations. These compounds were then investigated in vitro, for cytotoxicity against CSCs isolated from MDA-MB-231 triple negative breast cancer cells. Alpha-hederin (AH) was identified as the only compound in the selected library that has cytotoxicity against breast CSCs. AH was further investigated for it's ability to regulate Wnt pathway target genes (Cyclin D1 and CD44)and the tumor suppressor p53by real-time quantitative PCR. Absorption, distribution, metabolism, excretion and toxicity properties of the AH was predicted in silico. AH significantly down regulated the transcription of Cyclin D1 and CD44 while up-regulating the transcription of p53. AH was predicted to have acceptable drug likeness. Although AH is currently known to inhibit the growth of various cancer cells in vitro, present study demonstrated for the first time that it is a potent inhibitor of Wnt/β-catenin signaling pathway and induce apoptosis in breast CSCs.
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    Sympathy towards patients
    (Royal College of Physicians of London, 1999) Seneviratne, S.L.; Gunatilake, S.B.; Dassanayake, D.; Adhikari, A.; de Silva, H.J.
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