Influence of 17β-Estradiol on 15-Deoxy-Δ^12,14 Prostaglandin J₂ -Induced Apoptosis in MCF-7 and MDA-MB-231 Cells

Yaacob, Nik Soriani,Nasir, Rabail,Norazmi, Mohd Nor Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

The nuclear receptor, peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), is expressed in various cancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of $PPAR{\gamma}$, 15-deoxy-${\Delta}^{12,14}$ prostaglandin $J_2$ (PGJ2), is emerging as a potent anticancer agent but the exact mechanism has not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects of PGJ2 on estrogen receptor alpha ($ER{\alpha}$)-positive (MCF-7) and $ER{\alpha}$-negative (MDA-MB-231) human breast cancer cells. Based on the reported signalling cross-talk between $ER{\alpha}$ and $ER{\alpha}$, the effect of the $ER{\alpha}$ ligand, $17{\beta}$-estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we report that PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death with active involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but not in MDA-MB-231 cells. The $ER{\alpha}$ antagonist, GW9662, failed to block PGJ2-induced activities but potentiated its effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death. It can be concluded that E2 enhances $ER{\alpha}$-independent anticancer effects of PGJ2 in the presence of its receptor.

Cell Cycle Modulation of MCF-7 and MDA-MB-231 by a Sub-Fraction of Strobilanthes crispus and its Combination with Tamoxifen

Yaacob, Nik Soriani,Kamal, Nik Nursyazni Nik Mohamed,Wong, Kah Keng,Norazmi, Mohd Nor Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

Background: Cell cycle regulatory proteins are suitable targets for cancer therapeutic development since genetic alterations in many cancers also affect the functions of these molecules. Strobilanthes crispus (S. crispus) is traditionally known for its potential benefits in treating various ailments. We recently reported that an active sub-fraction of S. crispus leaves (SCS) caused caspase-dependent apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells. Materials and Methods: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle-related transcripts was analysed based on a previous microarray dataset. Results: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of $ER{\alpha}$ protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied. Conclusions: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.

Proliferation of Keratinocytes Induced by Adipose-Derived Stem Cells on a Chitosan Scaffold and Its Role in Wound Healing, a Review

Gomathysankar, Sankaralakshmi,Halim, Ahmad Sukari,Yaacob, Nik Soriani Korean Society of Plastic and Reconstructive Surge 2014 Archives of Plastic Surgery Vol.41 No.5

In the field of tissue engineering and reconstruction, the development of efficient biomaterial is in high demand to achieve uncomplicated wound healing. Chronic wounds and excessive scarring are the major complications of tissue repair and, as this inadequate healing continues to increase, novel therapies and treatments for dysfunctional skin repair and reconstruction are important. This paper reviews the various aspects of the complications related to wound healing and focuses on chitosan because of its unique function in accelerating wound healing. The proliferation of keratinocytes is essential for wound closure, and adipose-derived stem cells play a significant role in wound healing. Thus, chitosan in combination with keratinocytes and adipose-derived stem cells may act as a vehicle for delivering cells, which would increase the proliferation of keratinocytes and help complete recovery from injuries.

Proliferation of Keratinocytes Induced by Adipose- Derived Stem Cells on a Chitosan Scaffold and Its Role in Wound Healing, a Review

Sankaralakshmi Gomathysankar,Ahmad Sukari Halim,Nik Soriani Yaacob 대한성형외과학회 2014 Archives of Plastic Surgery Vol.41 No.5

In the field of tissue engineering and reconstruction, the development of efficient biomaterialis in high demand to achieve uncomplicated wound healing. Chronic wounds and excessivescarring are the major complications of tissue repair and, as this inadequate healing continuesto increase, novel therapies and treatments for dysfunctional skin repair and reconstructionare important. This paper reviews the various aspects of the complications related to woundhealing and focuses on chitosan because of its unique function in accelerating wound healing. The proliferation of keratinocytes is essential for wound closure, and adipose-derived stemcells play a significant role in wound healing. Thus, chitosan in combination with keratinocytesand adipose-derived stem cells may act as a vehicle for delivering cells, which would increasethe proliferation of keratinocytes and help complete recovery from injuries

Correlation of Tumour Response with Starting Tumour Size and Dose of Tamoxifen in an N-Methyl-N-Nitrosourea (NMU)-Induced Rat Mammary Cancer Model

Yankuzo, Hassan Muhammad,Emilia, Sharifah Tuan Sheriff,Shaari, Rumaizi,Yaacob, Nik Soriani Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: The aim of this preliminary study was to address variations of responses observed with different starting tumor sizes of 10 and 15 mm, and the effects of different doses of tamoxifen (TAM) on experimental rat mammary tumors. Materials and Methods: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and $500{\mu}g/day$) groups of six animals each, and another group (n=6) treated with TAM $100{\mu}g/day$ at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice. Results: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups. Conclusions: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.

15d-PGJ2 Induces Apoptosis of MCF-7 and MDA-MB-231 Cells via Increased Intracellular Calcium and Activation of Caspases, Independent of ERα and ERβ

Muhammad, Siti Nur Hasyila,Mokhtar, Noor Fatmawati,Yaacob, Nik Soriani Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

Reports indicate that 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2) has anticancer activities, but its mechanisms of action have yet to be fully elucidated. We therefore investigated the effects of 15d-PGJ2 on the human breast cancer cell lines, MCF-7 (estrogen receptor $ER{\alpha}+/ER{\beta}+$) and MDA-MB-231 ($ER{\alpha}-/ER{\beta}+$). Cellular proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays while apoptosis was determined by fluorescence microscopy and flow cytometry using annexin V-propidium iodide (PI) staining. ER expression was determined by Western blotting. Intracellular calcium was stained with Fluo-4 AM while intracellular caspase activities were detected with Caspase-$FLICA(R)$ and measured by flow cytometry. We showed that 15d-PGJ2 caused a significant increase in apoptosis in MCF-7 and MDA-MB-231 cells. $ER{\alpha}$ protein expression was reduced in treated MCF-7 cells but pre-incubation with the $ER{\alpha}$ inhibitor' ICI 182 780' did not affect the percentage of apoptotic cells. The expression of $ER{\beta}$ was unchanged in both cell lines. In addition, 15d-PGJ2 increased intracellular calcium ($Ca^{2+}$) staining and caspase 8, 9 and 3/7 activities. We therefore conclude that 15d-PGJ2 induces caspase-dependent apoptosis that is associated with an influx of intracellular $Ca^{2+}$ with no involvement of ER signaling.

The conserved and divergent roles of carbonic anhydrases in the filamentous fungi <i>Aspergillus fumigatus</i> and <i>Aspergillus nidulans</i>

Han, Kap-Hoon,Chun, Yoon-Hee,de Castro Pimentel Figueiredo, Bá,rbara,Soriani, Frederico Marianetti,Savoldi, Marcela,Almeida, Agostinho,Rodrigues, Fernando,Cairns, Charlie Timothy,Bignell, Elaine Blackwell Publishing Ltd 2010 Molecular microbiology Vol.75 No.6

<P>Summary</P><P>Carbon dioxide (CO<SUB>2</SUB>) and its hydration product bicarbonate (HCO<SUB>3</SUB><SUP>-</SUP>) are essential molecules in various physiological processes of all living organisms. The reversible interconversion between CO<SUB>2</SUB> and HCO<SUB>3</SUB><SUP>-</SUP> is in equilibrium. This reaction is slow without catalyst, but can be rapidly facilitated by Zn<SUP>2+</SUP>-metalloenzymes named carbonic anhydrases (CAs). To gain an insight into the function of multiple clades of fungal CA, we chose to investigate the filamentous fungi <I>Aspergillus fumigatus</I> and <I>A. nidulans</I>. We identified four and two CAs in <I>A. fumigatus</I> and <I>A. nidulans</I>, respectively, named <I>cafA-D</I> and <I>canA-B</I>. The <I>cafA</I> and <I>cafB</I> genes are constitutively, strongly expressed whereas <I>cafC</I> and <I>cafD</I> genes are weakly expressed but CO<SUB>2</SUB>-inducible. Heterologous expression of the <I>A. fumigatus cafB</I>, and <I>A. nidulans canA</I> and <I>canB</I> genes completely rescued the high CO<SUB>2</SUB>-requiring phenotype of a <I>Saccharomyces cerevisiae</I>&Dgr;<I>nce103</I> mutant. Only the &Dgr;<I>cafA</I>&Dgr;<I>cafB</I> and &Dgr;<I>canB</I> deletion mutants were unable to grow at 0.033% CO<SUB>2</SUB>, of which growth defects can be restored by high CO<SUB>2</SUB>. Defects in the CAs can affect <I>Aspergilli</I> conidiation. Furthermore, <I>A. fumigatus</I>&Dgr;<I>cafA</I>, &Dgr;<I>cafB</I>, &Dgr;<I>cafC</I>, &Dgr;<I>cafD</I> and &Dgr;<I>cafA</I>&Dgr;<I>cafB</I> mutant strains are fully virulent in a low-dose murine infection.</P>