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Fulltext Phytochemicals and Cytotoxicity of Quercus infectoria Ethyl Acetate Extracts on Human Cancer Cells

Yusof WNSW, Abdullah H

Trop Life Sci Res, 2020 Apr;31(1):69-84.
PMID: 32963712 DOI: 10.21315/tlsr2020.31.1.5

Conventional and modern cancer treatment were reported to manifest adverse effects to the patients. More researches were conducted to search for selective cytotoxic agent of plant natural product on cancer cells. The presences of wide range phytochemicals in Quercus infectoria (QI) extract have been implicated with the cytotoxic effect against various types of cancer cell which remain undiscovered. This present study aimed to evaluate cytotoxic effect of QI extracts on selected human cancer cells and then, the most potent extract was further analysed for general phytochemical constituents. QI galls were extracted successively with n-hexane, ethyl acetate and methanol yielded three main extracts; n-hexane (QIH), ethyl acetate (QIEA) and methanol (QIM), respectively. The most potent extract was qualitatively analysed for the present of tannin, alkaloids, glycosides, saponins, terpenoids, flavonoids and phenolic compounds. Next, the extracts were tested to determine the cytotoxic activity against cervical cancer cells (HeLa), breast cancer cells (MDA-MB-231) and liver cancer cells (Hep G2) using MTT assay. Cytotoxic activity of QI extracts against normal fibroblast (L929) cell line was also evaluated to determine the cytoselective property. Meanwhile, DMSO-treated cells served as negative control while cisplatin-treated cells served as positive control. The most potent extract then chosen to be further investigated for DNA fragmentation as hallmark of apoptosis using Hoechst staining. Qualitative phytochemical analysis revealed the presence of tannin, alkaloids, glycosides, saponins, terpenoids, flavonoids and phenolic compounds. QIEA extract exhibited the most potent cytotoxic activity against HeLa cells with (IC50 value = 6.33 ± 0.33 μg/mL) and showed cytoselective property against L929 cells. DNA fragmentation revealed QIEA induced apoptosis in the treated cells. The richness of phytochemical constituents in QIEA extract might contribute to the potency of cytotoxic activity towards HeLa cells.

Matched MeSH terms: Cisplatin
Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein

Ng WK, Yazan LS, Ismail M

Toxicol In Vitro, 2011 Oct;25(7):1392-8.
PMID: 21609759 DOI: 10.1016/j.tiv.2011.04.030

Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.

Matched MeSH terms: Cisplatin/pharmacology
Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis

Nna VU, Ujah GA, Suleiman JB, Mohamed M, Nwokocha C, Akpan TJ, et al.

Toxicology, 2020 08;441:152528.
PMID: 32565124 DOI: 10.1016/j.tox.2020.152528

Cisplatin (Cis) is an effective chemotherapeutic intervention against many cancer types. However, the oxidative stress-related toxicities associated with cancer cell resistance-induced dose scaling has limited its long-term use. In the present study, we explored the benefits of the antioxidant, tert-butylhydroquinone (tBHQ; 50 mg/kg b.w./day, for 14 days) against Cis single dose injection (7 mg/kg b.w., i.p on Day 8), on testicular toxicity of male Wistar rats. Cis triggered testicular and epididymal oxidative stress, testicular inflammation (upregulated NF-κB, TNF-α and IL-1β mRNA levels, and downregulated IL-10 mRNA level), increased testicular apoptosis (increased Bax/Bcl2 and caspase-3 mRNA levels) and decreased testicular germ cells proliferation. Further, Cis decreased testicular steroidogenesis (decreased expression of StAR, CYP11A1, 3β-HSD and 17β-HSD mRNA and proteins) and decreased follicle stimulating hormone, luteinizing hormone and testosterone levels. Cis also decreased sperm count, motility, viability, normal morphology and Johnsen score. However, intervention with tBHQ significantly decreased oxidative stress by upregulating Nrf2 gene, suppressed inflammation, apoptosis and increased testicular germ cells proliferation. tBHQ also increased steroidogenesis and improved sperm parameters. Taken together, tBHQ improves steroidogenesis and spermatogenesis in Cis-intoxicated rats by improving antioxidant status, dampening inflammation and apoptosis, thus improving the proliferative capacity of spermatogenic cells.

Matched MeSH terms: Cisplatin/antagonists & inhibitors; Cisplatin/toxicity*
Fulltext Epithelial-to-mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy

Poh ME, Liam CK, Mun KS, Chai CS, Wong CK, Tan JL, et al.

Thorac Cancer, 2019 09;10(9):1841-1845.
PMID: 31350945 DOI: 10.1111/1759-7714.13156

Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin-based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis.

Matched MeSH terms: Cisplatin/administration & dosage
Selectivity of compounds isolated from the leaves of Nerium indicum Mill. on various human cancer cell lines

Mae SH, Sofia M, Bolhuis RL, Nooter K, Oostrum RG, Subagus W, et al.

Med J Malaysia, 2008 Jul;63 Suppl A:24-5.
PMID: 19024965

The leaves of Nerium indicum Mill. have been utilized traditionally to cure cancer. By Bioassay (BST) guided isolation method, six compounds were isolated from the CHCl3 extract of the leaves. Selectivity of these compounds (in 0.6-12,500 ng/ml) was tested on various human cancer (MCF7, EVSA-T, T47D, H226, IGROV, A498, WIDR, M19, HeLa) and normal (Vero) cells in vitro. Doxorubicin and cysplatin were used as positive controls. The result indicated that NiO2D (5alpha-oleandrin) possessed the best cytotoxic effect on HeLa cells (IC50, 8.38 x10(-6) mM) and NiO2C (16, 17-dehidrodeasetil-5alpha-oleandrin) on A498 cells (IC50, 1.43 x 10(-6) mM). Those two compounds were not cytotoxic to normal cell.

Matched MeSH terms: Cisplatin/pharmacology; Cisplatin/therapeutic use
Fulltext Combination chemotherapy for small cell lung cancer

Sufarlan AW, Zainudin BM

Med J Malaysia, 1993 Jun;48(2):166-70.
PMID: 8394502

Small cell lung cancer (SCLC) disseminates early and has poor prognosis. However, SCLC is highly chemosensitive, thus chemotherapy has been established as the primary mode of treatment. Seventeen patients (15 males and 2 females) with median age of 60 years (range 49 to 74 years) were treated with combination cyclophosphamide 750 mg/m2, adriamycin 40 mg/m2, vincristine 1.4 mg/m2 on day 1 and etoposide (VP 16) 75 mg/m2 on days 1 to 3 (CAVE). This combination was given in 6 courses at 3 weekly intervals. The response to the chemotherapy and the quality of life of patients was assessed at the third cycle and after the completion of therapy (sixth cycle). The overall response rate was 76.4%; 52.9% achieved complete response and 23.5% had partial response. The survival rate at 6 months was 70.8% and 4 patients (23.5%) were still alive after 1 year of chemotherapy. The median survival after therapy was 36 weeks. There was a 30% overall improvement in the Karnofsky performance score at the completion of chemotherapy. This study illustrated that the CAVE regimen is effective and beneficial in the majority of our patients with small cell lung cancer.

Matched MeSH terms: Cisplatin/administration & dosage
Fulltext Ondansetron against metoclopramide/dexamethasone--a comparative study

Lim AKH, Haron MR, Yap TM

Med J Malaysia, 1994 Sep;49(3):231-8.
PMID: 7845271

This trial was carried out in Hospital Kuala Lumpur. Fifty-two patients who were scheduled to receive their first or subsequent courses of cancer chemotherapy with single dose cisplatinum containing chemotherapy regimens were evaluated. Thirty-four patients were given ondansetron in one group while 18 in the other group received metoclopramide with dexamethasone. The response to treatment was categorised as complete (0 emetic episode), major (1 or 2 emetic episodes), minor (3 to 5 emetic episodes) or failure (> 5 emetic episodes or rescue medication). Among the 52 patients, a complete or major control (0 to 2 emetic episodes) was achieved in 23/34 patients (68%) from the ondansetron group and in 3/18 patients (17%) from the metoclopramide with dexamethasone group (p < 0.002) on day 1. Similarly, the control of nausea was greater in the ondansetron group compared with the metoclopramide with dexamethasone group (p < 0.0009) on day 1. Two patients were excluded (dropped out) after day one from each of the two study groups due to excessive vomiting subsequent to cisplatinum therapy. From days 2 to 6, there was a trend in favour of ondansetron. Both treatments were well tolerated. The results of this trial show that in the prophylaxis of nausea and vomiting induced by cisplatinum containing chemotherapy, the efficacy of ondansetron is superior to that of a standard anti-emetic combination, metoclopramide with dexamethasone.

Matched MeSH terms: Cisplatin/adverse effects*
Myasthenia gravis and a rare complication of chemotherapy

Ng CV

Med J Aust, 2005 Feb 07;182(3):120.
PMID: 15698357

We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.

Matched MeSH terms: Cisplatin/administration & dosage
Beware the undescended testis and abdominal mass

Koh KB

Aust N Z J Surg, 1996 Dec;66(12):851-3.
PMID: 8996073

We report five patients who presented with seminoma of an undescended testis to highlight the importance of dealing with adult cryptorchidism. On the basis of the literature review and our experience, we advocate orchidectomy for post-pubertal cryptorchid patients of any age because follow-up may be difficult, and treatment for the tumour may be unsuccessful.

Matched MeSH terms: Cisplatin/administration & dosage
Adjuvant cytotoxic chemotherapy following Wertheim radical hysterectomy for cervical cancer

Sivanesaratnam V, Sen DK, Jayalakshmi P

Aust N Z J Obstet Gynaecol, 1987 Aug;27(3):231-3.
PMID: 2449159

Patients at high risk of recurrence or metastases following radical surgery for Stage 1B and 2A cervical carcinoma include those with pelvic node metastases, lymphatic or vascular space permeation in the cervix by tumour cells, large size of the primary tumour, involvement of the full thickness of the cervix and parametrial spread. We report the initial results of adjuvant chemotherapy using a combination of cisplatinum, bleomycin and vinblastine in 22 patients who had undergone Wertheim radical hysterectomy and were thought to be at high risk of developing recurrence. The mean duration of follow-up was 23 months. All are alive after follow-up ranging from 13 to 43 months. Three patients developed recurrences--one in the pelvis, another at the posterior aspect of the urethral meatus and the third developed pulmonary secondaries at 20 to 23 months after surgery. Toxicity from the chemotherapy was acceptable.

Matched MeSH terms: Cisplatin/administration & dosage
Fulltext Standardization and experience may influence the survival of laparoscopic radical hysterectomy for cervical cancer

Lee CL, Huang KG, Chua PT, Mendoza MCVR, Lee PS, Lai SY

Taiwan J Obstet Gynecol, 2021 May;60(3):463-467.
PMID: 33966729 DOI: 10.1016/j.tjog.2021.03.013

OBJECTIVE: Minimally invasive radical hysterectomy has been shown to be associated with poorer outcome in an influential prospective, randomized trial. However, many centers worldwide performing minimally invasive radical hysterectomy have data and experience that prove otherwise. We aim to review surgical and oncologic outcomes of patients operated by Laparoscopic Radical Hysterectomy in a tertiary hospital, by experienced surgeons and standardization in radicality, for cervical carcinoma Stage 1A1-1B1 from January 2009 to May 2014.
MATERIALS & METHODS: Standardised surgical technique with Parametrium & Paracolpium resection approach was adopted by qualified and experienced Gynecologic/Gyne-Oncologic Endoscopic & Minimally Invasive Surgeons in performing Laparoscopic Radical Hysterectomy for Cervical Cancer stage 1A1-1B1 from January 2009-May 2014, involving 53 patients. Electronic Medical Record system (EMR) Of Chang Gung Memorial Hospital(Tertiary Referral Centre), Department of Obstetrics & Gynecology was accessed for surgical and oncologic outcomes.
RESULTS: Fifty-Three patients operated from January 2009 to May 2014 were followed up for an average of 96.7 months with longest follow-up at 127 months. There were no cases of recurrence or death reported. 5 Year - Survival Rate and 5 Year Disease-Free Survival Rate were 100%. Two patients received post-operative pelvic radiation concurrent with chemotherapy using Cisplatin due to greater than 1/3 cervical stromal invasion.
CONCLUSION: It is vital to standardize minimally invasive surgical techniques for early stage cervical cancer, with focus on adequate radicality and resection which may contribute to excellent survival outcomes. Further international multi-center randomized trial (Minimally Invasive Therapy Versus Open Radical Hysterectomy In Cervical Cancer) will provide justification for continued practice of MIS in early stage cervical cancer.

Matched MeSH terms: Cisplatin
Rolapitant improves quality of life of patients receiving highly or moderately emetogenic chemotherapy

Chasen M, Urban L, Schnadig I, Rapoport B, Powers D, Arora S, et al.

Support Care Cancer, 2017 01;25(1):85-92.
PMID: 27557833

PURPOSE: Addition of rolapitant to standard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting (CINV) in phase 3 trials of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Here, we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis (FLIE).
METHODS: In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18-126]). We performed a prespecified analysis of the MEC/anthracycline-cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies.
RESULTS: In the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p

Matched MeSH terms: Cisplatin/administration & dosage; Cisplatin/adverse effects
Synthesis of a DNA-targeting nickel (II) complex with testosterone thiosemicarbazone which exhibits selective cytotoxicity towards human prostate cancer cells (LNCaP)

Heng MP, Sinniah SK, Teoh WY, Sim KS, Ng SW, Cheah YK, et al.

Spectrochim Acta A Mol Biomol Spectrosc, 2015 Nov 5;150:360-72.
PMID: 26057090 DOI: 10.1016/j.saa.2015.05.095

Testosterone thiosemicarbazone, L and its nickel (II) complex 1 were synthesized and characterized by using FTIR, CHN, (1)H NMR, and X-ray crystallography. X-ray diffraction study confirmed the formation of L from condensation of testosterone and thiosemicarbazide. Mononuclear complex 1 is coordinated to two Schiff base ligands via two imine nitrogens and two tautomeric thiol sulfurs. The cytotoxicity of both compounds was investigated via MTT assay with cisplatin as positive reference standard. L is more potent towards androgen-dependent LNCaP (prostate) and HCT 116 (colon). On the other hand, complex 1, which is in a distorted square planar environment with L acting as a bidentate NS-donor ligand, is capable of inhibiting the growth of all the cancer cell lines tested, including PC-3 (prostate). It is noteworthy that both compounds are less toxic towards human colon cell CCD-18Co. The intrinsic DNA binding constant (Kb) of both compounds were evaluated via UV-Vis spectrophotometry. Both compounds showed Kb values which are comparable to the reported Kb value of typical classical intercalator such as ethidium bromide. The binding constant of the complex is almost double compared with ligand L. Both compounds were unable to inhibit the action topoisomerase I, which is the common target in cancer treatment (especially colon cancer). This suggest a topoisomerase I independent-cell death mechanism.

Matched MeSH terms: Cisplatin
Fulltext Preliminary experience with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy in the treatment of advanced non-small cell lung cancer at University Hospital, Kuala Lumpur

Lee SM

Singapore Med J, 1990 Jun;31(3):228-32.
PMID: 2168091

Twelve patients with advanced inoperable non-small cell lung cancer (NSCLC) were treated with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy. The overall response rate was 33% (4 partial responses and no complete response) with a median survival of seven months. One responder above subsequently achieved complete remission following successful resection of his tumour and is still alive 14 months after initial chemotherapy. Responses were observed in patients with good performance status and limited disease. Side-effects were generally well tolerated and manageable. MVP is an effective regimen and the low response rate achieved here as compared to other centres is also discussed.

Matched MeSH terms: Cisplatin/therapeutic use
Fulltext Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2

Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.

Sci Rep, 2016 05 10;6:25650.
PMID: 27160553 DOI: 10.1038/srep25650

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

Matched MeSH terms: Cisplatin
Fulltext Mitochondrial DNA alterations may influence the cisplatin responsiveness of oral squamous cell carcinoma

Aminuddin A, Ng PY, Leong CO, Chua EW

Sci Rep, 2020 May 12;10(1):7885.
PMID: 32398775 DOI: 10.1038/s41598-020-64664-3

Cisplatin is the first-line chemotherapeutic agent for the treatment of oral squamous cell carcinoma (OSCC). However, the intrinsic or acquired resistance against cisplatin remains a major obstacle to treatment efficacy in OSCC. Recently, mitochondrial DNA (mtDNA) alterations have been reported in a variety of cancers. However, the role of mtDNA alterations in OSCC has not been comprehensively studied. In this study, we evaluated the correlation between mtDNA alterations (mtDNA content, point mutations, large-scale deletions, and methylation status) and cisplatin sensitivity using two OSCC cell lines, namely SAS and H103, and stem cell-like tumour spheres derived from SAS. By microarray analysis, we found that the tumour spheres profited from aberrant lipid and glucose metabolism and became resistant to cisplatin. By qPCR analysis, we found that the cells with less mtDNA were less responsive to cisplatin (H103 and the tumour spheres). Based on the findings, we theorised that the metabolic changes in the tumour spheres probably resulted in mtDNA depletion, as the cells suppressed mitochondrial respiration and switched to an alternative mode of energy production, i.e. glycolysis. Then, to ascertain the origin of the variation in mtDNA content, we used MinION, a nanopore sequencer, to sequence the mitochondrial genomes of H103, SAS, and the tumour spheres. We found that the lower cisplatin sensitivity of H103 could have been caused by a constellation of genetic and epigenetic changes in its mitochondrial genome. Future work may look into how changes in mtDNA translate into an impact on cell function and therefore cisplatin response.

Matched MeSH terms: Cisplatin/pharmacology*
Fulltext Alterations of microRNA expression patterns in human cervical carcinoma cells (Ca Ski) toward 1'S-1'-acetoxychavicol acetate and cisplatin

Phuah NH, In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH

Reprod Sci, 2013 May;20(5):567-78.
PMID: 23012319 DOI: 10.1177/1933719112459220

The aims of this study were to investigate the combined effects of a natural compound 1'S-1'-acetoxychavicol acetate (ACA) with cisplatin (CDDP) on HPV-positive human cervical carcinoma cell lines (Ca Ski-low cisplatin sensitivity and HeLa-high cisplatin sensitivity), and to identify microRNAs (miRNAs) modulated in response toward ACA and/or CDDP. It was revealed that both ACA and CDDP induced dose- and time-dependent cytotoxicity when used as a stand-alone agent, while synergistic effects were observed when used in combination with a combination index (CI) value of 0.74 ± 0.01 and 0.85 ± 0.01 in Ca Ski and HeLa cells, respectively. A total of 25 miRNAs were found to be significantly differentially expressed in response to ACA and/or CDDP. These include hsa-miR-138, hsa-miR-210, and hsa-miR-744 with predicted gene targets involved in signaling pathways regulating apoptosis and cell cycle progression. In conclusion, ACA acts as a chemosensitizer which synergistically potentiates the cytotoxic effect of CDDP in cervical cancer cells. The altered miRNA expression upon administration of ACA and/or CDDP suggests that miRNAs play an important role in anticancer drug responses, which can be manipulated for therapeutic purposes.

Matched MeSH terms: Cisplatin/pharmacology
Fulltext Pulchrin A, a New Natural Coumarin Derivative of Enicosanthellum pulchrum, Induces Apoptosis in Ovarian Cancer Cells via Intrinsic Pathway

Nordin N, Fadaeinasab M, Mohan S, Mohd Hashim N, Othman R, Karimian H, et al.

PLoS One, 2016;11(5):e0154023.
PMID: 27136097 DOI: 10.1371/journal.pone.0154023

Drug resistance presents a challenge in chemotherapy and has attracted research interest worldwide and particular attention has been given to natural compounds to overcome this difficulty. Pulchrin A, a new compound isolated from natural products has demonstrated novel potential for development as a drug. The identification of pulchrin A was conducted using several spectroscopic techniques such as nuclear magnetic resonance, liquid chromatography mass spectrometer, infrared and ultraviolet spectrometry. The cytotoxicity effects on CAOV-3 cells indicates that pulchrin A is more active than cisplatin, which has an IC50 of 22.3 μM. Significant changes in cell morphology were present, such as cell membrane blebbing and formation of apoptotic bodies. The involvement of phosphatidylserine (PS) in apoptosis was confirmed by Annexin V-FITC after a 24 h treatment. Apoptosis was activated through the intrinsic pathway by activation of procaspases 3 and 9 as well as cleaved caspases 3 and 9 and ended at the executioner pathway, with the occurrence of DNA laddering. Apoptosis was further confirmed via gene and protein expression levels, in which Bcl-2 protein was down-regulated and Bax protein was up-regulated. Furthermore, the CAOV-3 cell cycle was disrupted at the G0/G1 phase, leading to apoptosis. Molecular modeling of Bcl-2 proteins demonstrated a high- binding affinity, which inhibited the function of Bcl-2 proteins and led to cell death. Results of the current study can shed light on the development of new therapeutic agents, particularly, human ovarian cancer treatments.

Matched MeSH terms: Cisplatin/pharmacology
Fulltext Distance-Based and Low Energy Adaptive Clustering Protocol for Wireless Sensor Networks

Liaqat M, Gani A, Anisi MH, Ab Hamid SH, Akhunzada A, Khan MK, et al.

PLoS One, 2016 Sep 22;11(9):e0161340.
PMID: 27658194 DOI: 10.1371/journal.pone.0161340

A wireless sensor network (WSN) comprises small sensor nodes with limited energy capabilities. The power constraints of WSNs necessitate efficient energy utilization to extend the overall network lifetime of these networks. We propose a distance-based and low-energy adaptive clustering (DISCPLN) protocol to streamline the green issue of efficient energy utilization in WSNs. We also enhance our proposed protocol into the multi-hop-DISCPLN protocol to increase the lifetime of the network in terms of high throughput with minimum delay time and packet loss. We also propose the mobile-DISCPLN protocol to maintain the stability of the network. The modelling and comparison of these protocols with their corresponding benchmarks exhibit promising results.

Matched MeSH terms: Cisplatin
Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28

Wong PF, Cheong WF, Shu MH, Teh CH, Chan KL, AbuBakar S

Phytomedicine, 2012 Jan 15;19(2):138-44.
PMID: 21903368 DOI: 10.1016/j.phymed.2011.07.001

Bioactive compounds from the medicinal plant, Eurycoma longifolia Jack have been shown to promote anti-proliferative effects on various cancer cell lines. Here we examined the effects of purified eurycomanone, a quassinoid found in Eurycoma longifolia Jack extract, on the expression of selected genes of the A549 lung cancer cells. Eurycomanone inhibited A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg/ml. The concentration that inhibited 50% of cell growth (GI(50)) was 5.1 μg/ml. The anti-proliferative effects were not fully reversible following the removal of eurycomanone, in which 30% of cell inhibition still remained (p<0.0001, T-test). At 8 μg/ml (GI(70)), eurycomanone suppressed anchorage-independent growth of A549 cells by >25% (p<0.05, T-test, n=8) as determined using soft agar colony formation assay. Cisplatin, a chemotherapy drug used for the treatment of non small cell lung cancer on the other hand, inhibited A549 cells proliferation at concentrations ranging from 0.2 μg/ml to 15 μg/ml with a GI(50) of 0.58 μg/ml. The treatment with eurycomanone reduced the abundance expression of the lung cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB), annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house keeping genes. The mRNA expressions of all genes with the exception of PHB were significantly downregulated, 72 h after treatment (p<0.05, T-test, n=9). These findings suggest that eurycomanone at viable therapeutic concentrations of 5-20 μg/ml exhibited significant anti-proliferative and anti-clonogenic cell growth effects on A549 lung cancer cells. The treatment also resulted in suppression of the lung cancer cell tumor markers and several known cancer cell growth-associated genes.

Matched MeSH terms: Cisplatin/pharmacology

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