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Fulltext 3-Bromo-1-hydroxy-9,10-anthraquinone (BHAQ) inhibits growth and migration of the human breast cancer cell lines MCF-7 and MDA-MB231

Abu N, Akhtar MN, Ho WY, Yeap SK, Alitheen NB

Molecules, 2013 Aug 27;18(9):10367-77.
PMID: 23985955 DOI: 10.3390/molecules180910367

Breast cancer is becoming more prominent in women today. As of now, there are no effective treatments in treating metastatic breast cancer. We have tested the cytotoxic and anti-migration effects of BHAQ, a synthesized anthraquinone, on two breast cancer cell lines, MCF-7 and MDA-MB231. Anthraquinones are an interesting class of molecules that display a wide spectrum of biological applications, including anticancer properties. Cellular inhibition was tested through a MTT assay, double acridine orange/propidium iodide staining and FACS cell cycle analysis. Inhibition of migration was tested by the wound healing method, and migration through a Boyden chamber. BHAQ was cytotoxic towards both cell lines in a dose dependent and possibly cell-dependent manner. Additionally, BHAQ also inhibited the migration of the highly metastatic MDA-MB231 cell line.

Matched MeSH terms: Doxorubicin/pharmacology
A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells

Viswanathan G, Hsu YH, Voon SH, Imae T, Siriviriyanun A, Lee HB, et al.

Macromol Biosci, 2016 06;16(6):882-95.
PMID: 26900760 DOI: 10.1002/mabi.201500435

Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.

Matched MeSH terms: Doxorubicin/administration & dosage*; Doxorubicin/chemistry
A Dual Bioconjugated Virus-Like Nanoparticle as a Drug Delivery System and Comparison with a pH-Responsive Delivery System

Biabanikhankahdani R, Ho KL, Alitheen NB, Tan WS

Nanomaterials (Basel), 2018 Apr 13;8(4).
PMID: 29652827 DOI: 10.3390/nano8040236

Modifications of virus-like nanoparticles (VLNPs) using chemical conjugation techniques have brought the field of virology closer to nanotechnology. The huge surface area to volume ratio of VLNPs permits multiple copies of a targeting ligand and drugs to be attached per nanoparticle. By exploring the chemistry of truncated hepatitis B core antigen (tHBcAg) VLNPs, doxorubicin (DOX) was coupled covalently to the external surface of these nanoparticles via carboxylate groups. About 1600 DOX molecules were conjugated on each tHBcAg VLNP. Then, folic acid (FA) was conjugated to lysine residues of tHBcAg VLNPs to target the nanoparticles to cancer cells over-expressing folic acid receptor (FR). The result demonstrated that the dual bioconjugated tHBcAg VLNPs increased the accumulation and uptake of DOX in the human cervical and colorectal cancer cell lines compared with free DOX, resulting in enhanced cytotoxicity of DOX towards these cells. The fabrication of these dual bioconjugated nanoparticles is simple, and drugs can be easily conjugated with a high coupling efficacy to the VLNPs without any limitation with respect to the cargo's size or charge, as compared with the pH-responsive system based on tHBcAg VLNPs. These dual bioconjugated nanoparticles also have the potential to be modified for other combinatorial drug deliveries.

Matched MeSH terms: Doxorubicin
Fulltext A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery

Biabanikhankahdani R, Bayat S, Ho KL, Alitheen NBM, Tan WS

Sci Rep, 2017 Jul 13;7(1):5303.
PMID: 28706267 DOI: 10.1038/s41598-017-05525-4

pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.

Matched MeSH terms: Doxorubicin/metabolism*
A new mechanism of thermal sensitivity for rapid drug release and low systemic toxicity in hyperthermia and thermal ablation temperature ranges

Dabbagh A, Abdullah BJ, Abu Kasim NH, Abdullah H, Hamdi M

Int J Hyperthermia, 2015 Jun;31(4):375-85.
PMID: 25716769 DOI: 10.3109/02656736.2015.1006268

The aim of this paper was to introduce a new mechanism of thermal sensitivity in nanocarriers that results in a relatively low drug release at physiological temperature and rapid release of the encapsulated drug at hyperthermia and thermal ablation temperature range (40-60 °C).

Matched MeSH terms: Doxorubicin/pharmacology
Fulltext A pH-sensitive, biobased calcium carbonate aragonite nanocrystal as a novel anticancer delivery system

Shafiu Kamba A, Ismail M, Tengku Ibrahim TA, Zakaria ZA

Biomed Res Int, 2013;2013:587451.
PMID: 24324966 DOI: 10.1155/2013/587451

The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO₃/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO₃/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO₃/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO₃ nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.

Matched MeSH terms: Doxorubicin/administration & dosage*; Doxorubicin/chemistry
Fulltext Abdominal Lymphocyte-Depleted Hodgkin Lymphoma: A Rare Presentation

Kasinathan G, Kori AN, Hassan N

Int J Gen Med, 2019;12:405-409.
PMID: 31807052 DOI: 10.2147/IJGM.S232254

Background: Hodgkin lymphoma (HL) is a type of lymphoma that arises from the B lymphocytes. The four main subtypes of HL are the nodular sclerosing, mixed cellularity, lymphocyte rich and the lymphocyte depleted. Nodular sclerosis subtype accounts for majority of all classical HL, whereas lymphocytic depletion type accounts for less than 1%. The main objective of reporting this case is to share with the medical fraternity a rare presentation of abdominal lymphocyte-depleted classical Hodgkin lymphoma.
A 47-year-old gentleman of Malay ethnicity with no known pre-morbidities, presented to the haematology unit with a 2-month history of night fever, loss of weight, malaise, anorexia and abdominal swelling. Abdominal examination revealed a periumbilical and lower epigastric swelling measuring 6x6 cms. The swelling was non-tender, firm in consistency and smooth on palpation. The Contrast Enhanced Computed Tomography (CECT) imaging revealed an enlarged mesenteric mass measuring 5.8x6.9x5.7 cm and multiple enlarged aorta-caval lymph nodes. The mesenteric tumour histology and immunohistochemistry were consistent with lymphocyte depleted HL. He completed six cycles of intravenous ABVD polychemotherapy consisting of doxorubicin (Adriamycin) 25mg/m2, Bleomycin 10mg/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2. The Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET /CT) imaging post 2 cycles and 6 cycles of ABVD polychemotherapy showed complete metabolic response to chemotherapy.
Conclusion: Lymphocyte-depleted classical Hodgkin lymphoma (LDcHL) is a rare entity and is mostly diagnosed at a later stage rendering it a disease with poor prognostic outcomes. Early detection and prompt institution of therapy is crucial in the management of this disease.

Matched MeSH terms: Doxorubicin
Fulltext An online survey of Malaysian long-term e-cigarette user perceptions

Abdulrahman SA, Ganasegeran K, Loon CW, Rashid A

Tob Induc Dis, 2020;18:26.
PMID: 32292316 DOI: 10.18332/tid/118720

INTRODUCTION: The use of e-cigarettes (EC) has reached alarming proportions among Malaysians. On a national level, little is known about the profile and perceptions of Malaysian EC users. This study aimed to explore the prevalence of long-term EC usage and its associated factors among EC users in Malaysia.

METHODS: This nationwide online questionnaire survey was administered among 694 EC users across 13 states and 1 Federal Territory in Malaysia, between January and April 2018. A survey link was e-mailed to EC users that were recruited from an official national vape entity through their Facebook association page. We obtained information on respondents' sociodemographic characteristics, smoking habits, long-term e-cigarette usage and perceptions of EC use. We estimated long-term EC user prevalence and fitted multivariate regression models to predict factors associated with long-term EC usage. Statistical significance was set at p<0.05.

RESULTS: Respondents were predominantly Malays (87.6%), aged >30 years (68.1%) and tertiary educated (71%). The majority were employed (93.1%) with a monthly household income of MYR 4000 or less (56.6%). About 84% were former smokers, while 10% were current smokers. The prevalence of long-term EC usage in this study was 82.3%. Most users believed that EC had helped them to cut down tobacco smoking (94.8%), reduced the urge to smoke (88.3%) and ultimately helped them to quit smoking (87.2%). Respondents aged >30 years and those who perceived that EC has helped them stop smoking were significantly more likely to be long-term EC users.

CONCLUSIONS: Most respondents engaged in EC use to quit smoking. They were more likely to be long-term EC users if they were older and perceived that EC has helped them to quit smoking. This information is valuable for targeted prevention, health promotion and policy regulations.

Matched MeSH terms: Doxorubicin
Anticancer Evaluation of Novel Quinazolinone Acetamides: Synthesis and Characterization

Hakima F, Salfi R, Bhikshapathi D, Khan A

Anticancer Agents Med Chem, 2021 May 24.
PMID: 34030622 DOI: 10.2174/1871520621666210524164351

BACKGROUND: According to the global cancer report of 2019, the burden of cancer will exceed more than 18 million becoming one of the major causes of global mortality rate. There is a pressing need to establish novel drug candidates for cancer treatment, though many anticancer agents are available in the market owing to their adverse effects. In recent years, quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors.
OBJECTIVE: The objective of this study is to evaluate the anti-cancer potential of the novel class of quinazoline tethered acetamide derivatives against six different cancer cell lines.
METHOD: A novel series of various substituted quinazolinone acetamides were synthesized through a feasible scheme. The synthetic scheme involves the conversion of benzoxazinone (from anthranilic acid and benzoyl chloride) intermediate to 3-amino quinazoline-4-one which is further converted to the final amide by tethering with the propionyl chloride employing Schotten-Baumann Reaction conditions. All the synthesized derivatives characterized by IR, 1HNMR and MASS spectral methods and anti-cancer activity evaluated by employing MTT assay for six cancer cell lines and one normal human cell line.
RESULTS: All the synthesized compounds were screened for anti-cancer activity against six cancer cell lines, including A 549 (lung), DU 145 (prostate), HT 29 (colon), MCF-7 (breast), SiHA (cervical), B16F10 (mouse skin melanoma) and one normal human fibroblast cell lines. All the compounds displayed a decent cytotoxicity profile when compared with the standard drug, doxorubicin. Among the synthesized compounds (5a to 5n) tested, two compounds, 5f and 5g have demonstrated excellent cytotoxicity against SiHA and MCF-7 cancer cell lines.
CONCLUSION: Comparatively, most of the compounds displayed decent cytotoxicity potential relative to the standard drug, doxorubicin. Further investigations are needed to establish the detailed mechanism of action of the developed novel quinazolinone acetamides.

Matched MeSH terms: Doxorubicin
Apoptosis in Acanthamoeba castellanii belonging to the T4 genotype

Baig AM, Lalani S, Khan NA

J Basic Microbiol, 2017 Jul;57(7):574-579.
PMID: 28466971 DOI: 10.1002/jobm.201700025

Here we describe features of apoptosis in unicellular Acanthamoeba castellanii belonging to the T4 genotype. When exposed to apoptosis-inducing compounds such as doxorubicin, A. castellanii trophozoites exhibited cell shrinkage and membrane blebbing as observed microscopically, DNA fragmentation using agarose gel electrophoresis, and phosphatidylserine (PS) externalization using annexin V immunostaining. Overall, these findings suggest the existence of apoptosis in A. castellanii possibly mediated by intrinsic apoptotic cascade. Further research in this field could provide avenues to selectively induce apoptosis in A. castellanii by triggering intrinsic apoptotic cascade.

Matched MeSH terms: Doxorubicin/pharmacology
Fulltext Association of creatinine clearance with neutropenia in breast cancer patients undergoing chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC)

Montoya JE, Luna HG, Morelos AB, Catedral MM, Lava AL, Amparo JR, et al.

Med J Malaysia, 2013 Apr;68(2):153-6.
PMID: 23629563

Fluorouracil, doxorubicin, cyclophosphamide protocol (FAC) is a commonly used regimen for breast cancer due to its proven efficacy, acceptable toxicity, high affordability. While hepatic insufficiency dosing for doxorubicin and fluorouracil have been set, there is paucity of data in the literature on how to reduce doses in renal insufficiency. We sought to determine whether there is an association with pre-chemotherapy creatinine clearance, and the occurrence of clinically significant grade 3 to 5 neutropenia during the course of FAC chemotherapy.

Matched MeSH terms: Doxorubicin
Fulltext Bladder tumours - a review of 150 patients treated at the Institute of Urology and Nephrology General Hospital Kuala Lumpur

Mahamooth Z, Awang H

Med J Malaysia, 1983 Mar;38(1):4-8.
PMID: 6633334

One hundred and fifty patients with urothelial tumours were reviewed. They form the majority of patients with bladder cancer referred to the Institute of Urology over the past three years. From the study it becomes very apparent that the majority of patients are seen late in the course of their disease. The results of treatment of patients with early lesions have been satisfactory but the patients with late invasive lesions have very poor prognosis. A plea is made that one be more aware of this condition and that symptoms of haematuria and urinary tract infections should have a full urological assessment early.

Matched MeSH terms: Doxorubicin/therapeutic use
Cellular prion protein contributes to LS 174T colon cancer cell carcinogenesis by increasing invasiveness and resistance against doxorubicin-induced apoptosis

Chieng CK, Say YH

Tumour Biol., 2015 Sep;36(10):8107-20.
PMID: 25983001 DOI: 10.1007/s13277-015-3530-z

As the cellular prion protein (PrP(C)) has been implicated in carcinogenesis, we aimed to investigate the effects of cancer cell-specific PrP(C) overexpression from the invasion, metastasis, and apoptosis aspects, by performing cell motility assays, cell proliferation assays under anchorage-dependent and anchorage-independent conditions, and apoptosis evasion when subjected to multiple anti-cancer drugs. Overexpression of PrP(C) in LS 174T was achieved by stable transfection. PrP(C) overexpression was shown to increase cell proliferation in anchorage-dependent and anchorage-independent manners, as shown by more viable cells in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, more colonies formed in soft agar assay and increased resistance to anoikis in poly-2-hydroxyethyl methacrylate-coated surface. PrP(C) overexpression also increased cell motility and invasiveness of LS 174T. Cell adhesion to extracellular matrix using collagen- and fibronectin-coated surfaces revealed increased cell attachment in LS 174T cells overexpressing PrP(C). Analysis of apoptotic and necrotic cells by propidium iodide/annexin V-fluorescein isothiocyanate microscopy and 7-amino-actinomycin D/annexin V-phycoerythrin flow cytometry revealed that PrP(C) overexpression attenuated doxorubicin-induced apoptosis. Human apoptosis antibody array with 35 apoptosis-related proteins revealed that three inhibitor of apoptosis proteins (IAPs)-survivin, X-linked inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis protein-1 (cIAP-1)-were upregulated in LS 174T cells overexpressing PrP(C) in doxorubicin-induced apoptosis. In conclusion, the overexpression of PrP(C) could enhance the invasiveness and survival of LS 174T colorectal cancer cells, indicating that PrP(C) plays a role in colorectal cancer biology.

Matched MeSH terms: Doxorubicin/pharmacology*
Fulltext Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells

Haque ST, Islam RA, Gan SH, Chowdhury EH

Int J Mol Sci, 2020 Sep 14;21(18).
PMID: 32937817 DOI: 10.3390/ijms21186721

Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5-6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.

Matched MeSH terms: Doxorubicin/pharmacology*; Doxorubicin/chemistry*
Fulltext Chemotherapy in nasopharyngeal carcinoma: review of results at University Hospital, Kuala Lumpur

Khanijow VK, Prasad U, Chang CM

Med J Malaysia, 1989 Dec;44(4):329-33.
PMID: 2520043

Nasopharyngeal carcinoma (NPC) is one of the commonest presentation of head and neck cancers in Malaysia, especially in the Chinese. The standard treatment is radical radiotherapy to the post-nasal space and the neck. Chemotherapy is given to patients with primary advanced disease and to patients with recurrence. The study reviews results of chemotherapy given to 33 patients at the University Hospital, Kuala Lumpur, over the last four years.

Matched MeSH terms: Doxorubicin/therapeutic use
Fulltext Chia Seed Oil Ameliorates Doxorubicin-Induced Cardiotoxicity in Female Wistar Rats: An Electrocardiographic, Biochemical and Histopathological Approach

Ahmed AZ, Mumbrekar KD, Satyam SM, Shetty P, D'Souza MR, Singh VK

Cardiovasc Toxicol, 2021 Jul;21(7):533-542.
PMID: 33740233 DOI: 10.1007/s12012-021-09644-3

Doxorubicin (DOX) is a potent anti-cancer antibiotic that was widely used for treatment of various cancers. It produces free radicals which result in extreme dose-limiting cardiotoxicity. This study investigated the cardioprotective potential of chia seed oil, an active polyphenolic nutraceutical against doxorubicin-induced cardiotoxicity in Wistar rats. Twenty-four female Wistar rats were divided into four groups (n = 6) which consist of normal control, DOX control, test-A and test-B group. Animals were prophylactically treated with two different doses of test drug, i.e. chia seed oil 2.5 ml/kg/day and 5 ml/kg/day in test-A and test-B groups orally for 7 days. Doxorubicin (25 mg/kg; single dose) was administered intraperitoneally to DOX control, Test-A and Test-B animals on the seventh day to induce cardiotoxicity. ECG analysis was done before and after treatment. Besides ECG, CK, CK-MB, LDH, AST, MDA and GSH were analyzed. DOX had significantly altered ECG, CK, CK-MB, LDH, AST, MDA and GSH. Pre-treatment with chia seed oil significantly alleviated DOX-induced ECG changes and also guarded against DOX-induced rise of serum CK, CK-MB and AST levels. Chia seed oil alleviated histopathological alteration in DOX-treated rats. It also significantly inhibited DOX-induced GSH depletion and elevation of MDA. The present study revealed that chia seed oil exerts cardioprotection against doxorubicin-induced cardiotoxicity in female Wistar rats. Our study opens the perspective to clinical studies to precisely consider chia seed oil as a potential chemoprotectant nutraceutical in the combination chemotherapy with doxorubicin to limit its cardiotoxicity.

Matched MeSH terms: Doxorubicin
Fulltext Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells

Ibiyeye KM, Zuki ABZ

Int J Mol Sci, 2020 Mar 10;21(5).
PMID: 32164352 DOI: 10.3390/ijms21051900

Cancer stem cells CSCs (tumour-initiating cells) are responsible for cancer metastasis and recurrence associated with resistance to conventional chemotherapy. This study generated MBA MD231 3D cancer stem cells enriched spheroids in serum-free conditions and evaluated the influence of combined doxorubicin/thymoquinone-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles. Single loaded drugs and free drugs were also evaluated. WST assay, sphere forming assay, ALDH activity analysis, Surface marker of CD44 and CD24 expression, apoptosis with Annexin V-PI kit, cell cycle analysis, morphological changes using a phase contrast light microscope, scanning electron microscopy, invasion assay and migration assay were carried out; The combination therapy showed enhanced apoptosis, reduction in ALDH activity and expression of CD44 and CD24 surface maker, reduction in cellular migration and invasion, inhibition of 3D sphere formation when compared to the free drugs and the single drug-loaded nanoparticle. Scanning electron microscopy showed poor spheroid formation, cell membrane blebbing, presence of cell shrinkage, distortion in the spheroid architecture; and the results from this study showed that combined drug-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles can efficiently destroy the breast CSCs compared to single drug-loaded nanoparticle and a simple mixture of doxorubicin and thymoquinone.

Matched MeSH terms: Doxorubicin/pharmacology*; Doxorubicin/chemistry
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: Doxorubicin/administration & dosage
Fulltext Combinatorial Cytotoxic Effects of Damnacanthal and Doxorubicin against Human Breast Cancer MCF-7 Cells in Vitro

Aziz MY, Abu N, Yeap SK, Ho WY, Omar AR, Ismail NH, et al.

Molecules, 2016 Sep 14;21(9).
PMID: 27649120 DOI: 10.3390/molecules21091228

Despite progressive research being done on drug therapy to treat breast cancer, the number of patients succumbing to the disease is still a major issue. Combinatorial treatment using different drugs and herbs to treat cancer patients is of major interest in scientists nowadays. Doxorubicin is one of the most used drugs to treat breast cancer patients. The combination of doxorubicin to other drugs such as tamoxifen has been reported. Nevertheless, the combination of doxorubicin with a natural product-derived agent has not been studied yet. Morinda citrifolia has always been sought out for its remarkable remedies. Damnacanthal, an anthraquinone that can be extracted from the roots of Morinda citrifolia is a promising compound that possesses a variety of biological properties. This study aimed to study the therapeutic effects of damnacanthal in combination with doxorubicin in breast cancer cells. Collectively, the combination of both these molecules enhanced the efficacy of induced cell death in MCF-7 as evidenced by the MTT assay, cell cycle, annexin V and expression of apoptosis-related genes and proteins. The effectiveness of doxorubicin as an anti-cancer drug was increased upon addition of damnacanthal. These results could provide a promising approach to treat breast cancer patients.

Matched MeSH terms: Doxorubicin/pharmacology; Doxorubicin/chemistry
Fulltext Comparison of doxorubicin anticancer drug loading on different metal oxide nanoparticles

Javed KR, Ahmad M, Ali S, Butt MZ, Nafees M, Butt AR, et al.

Medicine (Baltimore), 2015 Mar;94(11):e617.
PMID: 25789952 DOI: 10.1097/MD.0000000000000617

Nanomaterials are being vigorously investigated for their use in anticancer drug delivery regimes or as biomarkers agents and are considered to be a candidate to provide a way to combat severe weaknesses of anticancer drug pharmacokinetics, such as their nonspecificity. Because of this weakness, a bigger proportion of the drug-loaded nanomaterials flow toward healthy tissues and result in undesirable side effects. It is very important to evaluate drug loading and release efficiency of various nanomaterials to find out true pharmacokinetics of these drugs.This observational study aims to evaluate various surface functionalized and naked nanomaterials for their drug loading capability and consequently strengthens the Reporting of Observational Studies in Epidemiology (STROBE). We analyzed naked and coated nanoparticles of transition metal oxides for their further loading with doxorubicin, a representative water-soluble anticancer drug.Various uncoated and polyethylene glycol-coated metal oxide nanoparticles were synthesized and loaded with anticancer drug using simple stirring of the nanoparticles in a saturated aqueous solution of the drug. Results showed that surface-coated nanoparticles have higher drug-loading capabilities; however, certain naked metal oxide nanoparticles, such as cobalt oxide nanoparticles, can load a sufficient amount of drug.

Matched MeSH terms: Doxorubicin/administration & dosage*; Doxorubicin/chemistry

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