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Fulltext Aloe emodin enhances tamoxifen cytotoxicity effect on ER a-positive breast cancer cells, MCF-7, through downregulation of MEK1 and MEK2

Amin, I.M., Sheikh Abdul Kadir, S.H., Isa, M.R., Rosdy. N.M.M.N.M., Hasani NAH

JUMMEC, 2016;19(1):1-10.
MyJurnal

The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many
of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from
the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast
cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-
10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of
MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone
or a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time points
of 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifen
required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using
trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes
of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was
evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of
tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a
rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen
on the viability of ERa-positive-breast cancer cells.
A single targeted gamma-ray irradiation induced an acute modulation of immune cells and related cytokines in EMT6 mouse-bearing tumour model

Hasan N, Hasani NAH, Omar E, Sham FR, Fuad SBSA, Karim MKA, et al.

Cancer Biomark, 2023;38(1):61-75.
PMID: 37522193 DOI: 10.3233/CBM-220268

BACKGROUND: A complicated interplay between radiation doses, tumour microenvironment (TME), and host immune system is linked to the active participation of immune response.
OBJECTIVE: The effects of single targeted 2 Gy and 8 Gy gamma-ray irradiations on the immune cell population (lymphocytes, B-cells, T-cells, neutrophils, eosinophils, and macrophages) in EMT6 mouse-bearing tumour models was investigated.
METHODS: The effects of both irradiation doses in early (96 hours) and acute phase (5 to 11 days) post-irradiation on immune parameters were monitored in blood circulation and TME using flow cytometry. Simultaneously, selected cytokines related to immune cells within the TME were measured using multiplex ELISA.
RESULTS: A temporary reduction in systemic total white blood count (TWBC) resulted from an early phase (96 hours) of gamma-ray irradiation at 2 Gy and 8 Gy compared to sham control group. No difference was obtained in the acute phase. Neutrophils dominated among other immune cells in TME in sham control group. Eosinophils in TME was significantly increased after 8 Gy treatment in acute phase compared to sham control (p< 0.005). Furthermore, the increment of tumour necrosis (TNF)-α, eotaxin and interleukin (IL)-7 (p< 0.05) in both treatment groups and phases were associated with anti-tumour activities within TME by gamma-ray irradiation.
CONCLUSION: The temporary changes in immune cell populations within systemic circulation and TME induced by different doses of gamma-ray irradiation correlated with suppression of several pro-tumorigenic cytokines in mouse-bearing EMT6 tumour models.
Fulltext Acquired radioresistance in EMT6 mouse mammary carcinoma cell line is mediated by CTLA-4 and PD-1 through JAK/STAT/PI3K pathway

Sham NFR, Hasani NAH, Hasan N, Karim MKA, Fuad SBSA, Hasbullah HH, et al.

Sci Rep, 2023 Feb 22;13(1):3108.
PMID: 36813833 DOI: 10.1038/s41598-023-29925-x

Cancer recurrence is often associated with the acquisition of radioresistance by cancer tissues due to failure in radiotherapy. The underlying mechanism leading to the development of acquired radioresistance in the EMT6 mouse mammary carcinoma cell line and the potential pathway involved was investigated by comparing differential gene expressions between parental and acquired radioresistance cells. EMT6 cell line was exposed to 2 Gy/per cycle of gamma-ray and the survival fraction between EMT6-treated and parental cells was compared. EMT6RR_MJI (acquired radioresistance) cells was developed after 8 cycles of fractionated irradiation. The development of EMT6RR_MJI cells was confirmed with further irradiation at different doses of gamma-ray, and both the survival fraction and migration rates were measured. Higher survival fraction and migration rates were obtained in EMT6RR_MJI cells after exposure to 4 Gy and 8 Gy gamma-ray irradiations compared to their parental cells. Gene expression between EMT6RR_MJI and parental cells was compared, and 16 genes identified to possess more than tenfold changes were selected and validated using RT-PCR. Out of these genes, 5 were significantly up-regulated i.e., IL-6, PDL-1, AXL, GAS6 and APCDD1. Based on pathway analysis software, the development of acquired radioresistance in EMT6RR_MJI was hypothesized through JAK/STAT/PI3K pathway. Presently, CTLA-4 and PD-1 were determined to be associated with JAK/STAT/PI3K pathway, where both their expressions were significantly increased in EMT6RR_MJI compared to parental cells in the 1st, 4th and 8th cycle of radiation. As a conclusion, the current findings provided a mechanistic platform for the development of acquired radioresistance in EMT6RR_MJI through overexpression of CTLA-4 and PD-1, and novel knowledge on therapeutic targets for recurrent radioresistant cancers.
Fulltext Development of custom lead shield and strainer for targeted irradiation for mice in the gamma cell chamber

Hasan N, Sham NFR, Karim MKA, Fuad SBSA, Hasani NAH, Omar E, et al.

Sci Rep, 2021 Jul 15;11(1):14559.
PMID: 34267293 DOI: 10.1038/s41598-021-93964-5

We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the mice-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites.
Fulltext Profiling Insecticide Susceptibility of Aedes Albopictus From Hot Springs in Selangor, Malaysia

Wan-Norafikah O, Hasani NAH, Nabila AB, Najibah I, Nurjuani AHH, Masliana M, et al.

J Am Mosq Control Assoc, 2023 Sep 01;39(3):183-191.
PMID: 37796735 DOI: 10.2987/23-7125

The present study establishes insecticide susceptibility profiles of Aedes albopictus adult populations from 4 hot springs in Selangor, Malaysia, against 7 pyrethroids through an adult mosquito susceptibility bioassay. All Ae. albopictus populations were subjected to a 1-h exposure to each pyrethroid following the World Health Organization. The mortalities were recorded at 60 min of exposure to bifenthrin, 30 min for other pyrethroids, and 24 h posttreatment for all pyrethroids. Complete mortalities were observed upon exposures to the pyrethroids under 60 min and at 24 h posttreatment, excluding permethrin 0.25%, alpha-cypermethrin 0.05%, and bifenthrin 0.2%. These findings indicated that permethrin, deltamethrin, lambda-cyhalothrin, cyfluthrin, and etofenprox possess the recommended pyrethroid adulticide active ingredients that could be applied in vector control programs at these hot springs in the future. Nevertheless, the application of pyrethroids should be carefully monitored in rotation with other insecticide classes, including organophosphates and carbamates to avoid the development of insecticide resistance among mosquito vectors towards all insecticides. Although there were no reported cases of Aedes-borne pathogens at these hot springs to date, the current study results could still assist the Malaysian health authorities in determining approaches to control Aedes populations in these hot springs, if required in the future.