PMID- 32277652 OWN - NLM STAT- MEDLINE DCOM- 20201209 LR - 20220218 IS - 2241-6293 (Electronic) IS - 1107-0625 (Linking) VI - 25 IP - 1 DP - 2020 Jan-Feb TI - Kutkoside-an iridoid glycoside, exerts anti-proliferative effects in drug-resistant human oral carcinoma cells by targeting PI3K/AKT signalling pathway, inducing apoptosis and suppressing cell migration and invasion. PG - 338-343 AB - PURPOSE: The main purpose of the current research work was to investigate the anticancer potential of Kutkoside -a naturally occurring iridoid glycoside, against drug-resistant human oral carcinoma cells along with evaluating its effects on PI3K/AKT signalling pathway, cellular apoptosis, cell migration and cell invasion. METHODS: Cell viability was assessed by using MTT colorimetric assay, while effects on cellular apoptosis were evaluated by acridine orange (AO)/ethidium bromide (EB) as well as by using flow cytometry employing annexin V-FITC. Effects on cell migration and cell invasion were evaluated by in vitro wound healing assay and transwell Matrigel assay. Effects on PI3K/AKT signalling pathway were evaluated by western blot method. RESULTS: Kutkoside led to significant and dose-dependent inhibition of HSC-2 human oral cancer cells using doses of 0, 1.25, 2.5, 5, 10, 20, 40, 80 and 160 muM. Fluorescence microscopy revealed that on increasing the dose of kutkoside, the number of both apoptotic and necrotic cells increased, showing that Kutkoside induces apoptotic cell death in HSC-2 oral cancer cell line in dose-dependent manner. Flow cytometry indicated that the percentage of apoptotic cells at different dose exposures of Kutkoside, namely 0, 8, 16 and 32 muM was 4.9%, 12.18%, 22.18% and 34.10%, respectively. Kutkoside treatment also led to cell migration inhibition and cell invasion inhibition. This molecule upregulated the expression of AKT and PI3K, simultaneously downregulating the expressions of p-AKT and p-PI3K in a dose-dependent manner. CONCLUSION: Kutkoside shows potential anticancer and pro-apoptotic effects in HSC-2 oral carcinoma cells and as such may be developed as a possible anticancer agent provided further studies are performed. FAU - Hou, Jun-Chi AU - Hou JC AD - Department of Stomatology, Jining No.1 People's Hospital, Jining 272000 , Shandong, China. FAU - Xu, Xiao Nan AU - Xu XN LA - eng PT - Journal Article PT - Retracted Publication PL - Cyprus TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (Cinnamates) RN - 0 (Glucosides) RN - 0 (kutkoside) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM RIN - JBUON 2021 November-December; 26(6): 2714 ECI - J BUON. 2021 May-Jun;26(3):1179. PMID: 34268996 MH - Apoptosis MH - Cell Line, Tumor MH - Cell Movement MH - Cinnamates/pharmacology/*therapeutic use MH - Glucosides/pharmacology/*therapeutic use MH - Humans MH - Mouth Neoplasms/*drug therapy/pathology MH - Neoplasm Invasiveness MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction EDAT- 2020/04/12 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/04/12 06:00 PHST- 2020/04/12 06:00 [entrez] PHST- 2020/04/12 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PST - ppublish SO - J BUON. 2020 Jan-Feb;25(1):338-343.