Improving the therapeutic index of anthracycline chemotherapy: Focus on liposomal doxorubicin (Myocet™)

Leonard, Robert; Williams, S.; Tulpule, A.; Levine, A. M.; Oliveros, S.

doi:10.1016/j.breast.2009.05.004

Cited by 221 publications

(117 citation statements)

References 51 publications

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“…Apart from destroying adjacent normal cells (11), these treatments also cause severe side effects (12)(13)(14). Therefore, current studies have focused on the search for alternative medicines from plant-based sources.…”

Section: Introductionmentioning

confidence: 99%

Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines

et al. 2017

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Abstract. Cancer is a major public health concern not only in developed countries, but also in developing countries. It is one of the leading causes of mortality worldwide. However, current treatments may cause severe side effects and harm. Therefore, recent research has been focused on identifying alternative therapeutic agents extracted from plant-based sources in order to develop novel treatment options for cancer. Strobilanthes crispa Blume is a plant native to countries including Madagascar and Indonesia. It has been used as an anti-diabetic, diuretic and laxative in traditional folk medicine. Furthermore, S. crispa has potential in treating cancer, as evidenced in previous studies. In the present study, the cytotoxic and apoptotic activities of S. crispa crude extracts were investigated in liver and breast cancer cell lines. Hexane, ethyl acetate, chloroform, methanol and water extracts prepared from the leaves, and stems of S. crispa were evaluated for their cytotoxicity on HepG-2 and MDA-MB-231 cells using an MTT assay. The anti-proliferative properties of stem hexane (SH) extract on both cell lines were analysed using cell doubling time determination and cell cycle analysis, while the apoptogenic properties was determined through the detection of caspase-8. Among the extracts tested, SH extract exhibited the lowest half maximal inhibitory concentrations in both the cell lines. The SH extract induced morphological changes in HepG-2 and MDA-MB-231 cells, and significantly delayed cell population doubling time. Furthermore, it altered cell cycle profile and significantly increased caspase-8 activity in HepG-2 cells, but not in MDA-MB-231 cells. In conclusion, the SH extract of S. crispa possesses potent anticancer properties and may be a suitable chemotherapeutic target. IntroductionCancer is characterized by uncontrolled growth and spreading of abnormal cells. It is one of the most life-threatening and challenging diseases of modern time, caused by a number of internal factors, including immune condition and inherited mutation, and external factors, including radiation, tobacco and chemical exposure (1). Liver, breast, colorectal, lung, cervical and nasopharyngeal cancer are the most prevalent cancer types in the modern age. The present study focused on liver and breast cancer due to their high occurrence rates. In 2006, hepatocellular carcinoma (HCC) was identified to account for 70-85% of total primary liver cancer types (2). HCC is primarily caused by chronic viral hepatitis B or C infection, iron overload, aflotoxin exposure, obesity, alcohol-associated cirrhosis and possibly non-alcoholic fatty liver disease (3,4). Breast cancer continues to be the leading cause of cancer-associated mortality among women (5), and the occurrence rate has increased in China and other Asian countries (6,7). Breast cancer can be categorized into two main types, ductal carcinoma and lobular carcinoma. Ductal carcinoma begins in the ducts that transport milk from the breast to the nipple, whereas lobular carcinoma starts i...

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Section: Introductionmentioning

confidence: 99%

Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines

et al. 2017

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“…In the current study, we further demonstrated that the combination of liposomal M-V-05 with a pegylated liposome formulation of doxorubicin would yield additive cancer cell killing effect, with the potential of reducing the dose of liposomal doxorubicin needed for the same biological effect. As the pegylated liposome doxorubicin could give rise to palmar-plantar erythrodysesthesia (or hand-foot syndrome) with an overall incidence of 48% in MBC patients (24), it is thus beneficial to be able to reduce the dose of liposomal doxorubicin through the combinatorial use with liposomal M-V-05. In conclusion, liposomal M-V-05 is an effective therapy for breast cancer, and could be a novel adjuvant to liposomal doxorubicin therapy.…”

Section: Discussionmentioning

confidence: 99%

Liposomal M-V-05: Formulation development and activity testing of a novel dihydrofolate reductase inhibitor for breast cancer therapy

Tan

Quek²,

Wong³

et al. 2010

Int J Oncol

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Abstract. In the management of metastatic breast cancer, fewer recognized therapeutic standards are available as compared to the early stages of the disease. Thus, it is pertinent to search for new, effective therapy to improve survival, tolerability and quality of life of patients. In this study, a liposomal formulation was developed for a novel dihydrofolate reductase (DHFR) inhibitor, M-V-05. Drug encapsulation into liposomes was achieved by the citrate-based, pH gradient loading technique, with a final drug-to-lipid weight ratio of 0.1:1. The liposome formulation exhibited a sustained release profile of the encapsulated drug that followed first order release kinetics. Liposomal M-V-05 was found to be more effective than the standard DHFR inhibitor, methotrexate, and its activity was comparable to liposomal doxorubicin, with IC 50 values of 37 and 59 μM achieved in MDA-MB-231 and JIMT-1 cells, respectively. Similar cytotoxicity was observed in primary patient samples of invasive ductal carcinoma of the breast. The combination of liposomal M-V-05 and liposomal doxorubicin in fixed molar ratio of 3:1 was additive in cytotoxicity, allowing the concentrations of liposomal doxorubicin and liposomal M-V-05 to be reduced by 62 and 46%, respectively. Taken together, liposomal M-V-05 represents a promising agent and offers a potential new adjuvant therapy for breast cancer treatment.

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“…[5][6][7] The US Food and Drug Administration has approved for cancer therapy the use of doxorubicin encapsulated in liposomes (Doxil) and paclitaxel attached to nanoparticles (Abraxane). 8,9 In cancer chemotherapy, the clinician aims to achieve a good therapeutic index, which is the ratio of the lethal dose for 50% of the population to the minimum effective dose for 50% of the population. 10 But cancer is most often…”

Section: Introductionmentioning

confidence: 99%

In vivo assessment of bone marrow toxicity by gold nanoparticle-based bioconjugates in Crl:CD1(ICR) mice

Berce¹,

Lucan²,

Petrushev

et al. 2016

IJN

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Introduction The present study aimed at evaluating the biodistribution of Tween ® 20-gold nanoparticle (GNP) conjugates and their potential toxicity on the bone marrow before moving on to Phase I clinical trials. Materials and methods Tween ® 20-conjugated GNPs were injected intravenously for 21 days in male Crl:CD1(ICR) mice. Body weight of the mice was evaluated each day. After the sub-chronic Tween ® 20-GNPs administration, blood samples were harvested, and a full blood count was done individually. Total Au quantity from all major organs was assessed using inductively coupled plasma mass spectrometry. One femur and the sternum obtained from each animal were used for histological assessment. Results Our data showed that the Tween ® 20-GNP conjugates were found in large quantities in the bladder. Au was shown to accumulate in the hematopoietic bone tissue, with significant side effects such as leucopoiesis and megakaryopoiesis. The mice had a higher white blood cell and platelet count as opposed to the control group. This suggested that the previously described leukopenic effects of isoflurane were overridden by the leucopoietic effects of Tween ® 20-GNPs. Conclusion It was uncertain whether the mice were reactive to Au as it is a foreign substance to the tissues or whether the side effects observed were a precursor condition of a more severe hematological condition. Au was found to be hepatotoxic, urging the need for further studies in order to achieve better in vivo compliance and exploit the immense potential of GNPs in cancer pharmacology.

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Improving the therapeutic index of anthracycline chemotherapy: Focus on liposomal doxorubicin (Myocet™)

Cited by 221 publications

References 51 publications

Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines

Anticancer mechanisms of Strobilanthes crispa Blume hexane extract on liver and breast cancer cell lines

Liposomal M-V-05: Formulation development and activity testing of a novel dihydrofolate reductase inhibitor for breast cancer therapy

In vivo assessment of bone marrow toxicity by gold nanoparticle-based bioconjugates in Crl:CD1(ICR) mice

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