Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin

Scambia, Giovanni; Vincenzo, Rosa De; Ranelletti, P.O.; Panici, P. Benedetti; Ferrandina, Gabriella; D'Agostino, Giuseppe Roberto; Fattorossi, Andrea; Bombardelli, Ezio; Mancuso, Stefano

doi:10.1016/0959-8049(96)00011-1

Cited by 99 publications

(62 citation statements)

References 22 publications

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“…Studies conducted by us and others revealed that silibinin exerts synergistic anti-cancer effects with chemotherapeutic drugs such as doxorubicin, cisplatin and carboplatin in human breast carcinoma MCF-7 and MDA-MB468 cells (Scambia et al, 1996;; however, there is only one study where authors studied the in vivo cancer preventive efficacy in rat model of mammary carcinogenesis. Contrary to anticancer efficacy of silymarin against breast cancer cell lines, in this model, dietary supplementation of silymarin modestly increased the number of mammary tumors in 1-methyl-1-nitrosourea (MNU) treated animals.…”

Section: Breast Cancermentioning

confidence: 99%

“…We were the first one to demonstrate the anti-tumor promoting activity of silymarin against 12-Otetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in mouse epidermis, which was attributed to its ability to inhibit the activity and expression of epidermal ornithine decarboxylase (Agarwal et al, 1994). Anticancer activity of silymarin or silibinin has been observed against breast cancer (Zi et al, 1998, skin cancer (Ahmad et al, 1998, Lahiri-Chatterjee et al, 1999, androgen-dependent and-independent prostate cancer (Zi and Agarwal, 1999;Zi et al,2000;Bhatia et al, 1999;Deep et al, 2006;Thelen et al, 2004) cervical cancer (Bhatia et al, 1999), bladder cancer , hepatocellular carcinoma (Varghese et al, 2005), colon cancer , ovarian cancer (Scambia et al, 1996) and lung cancer (Sharma et al, 2003, Chu et al, 2004. Findings of these in vitro studies in various cancer cell culture systems have provided the platform for further research to explore their efficacy under in vivo conditions, and finally clinical application of this non-toxic agent as potential chemopreventive in cancer patients.…”

Section: Anticancer and Cancer Preventive Efficacy Of Silymarinmentioning

confidence: 99%

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Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

Kaur

Agarwal

2007

Toxicology and Applied Pharmacology

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Failure and high systemic toxicity of conventional cancer therapies have accelerated the focus on the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Silymarin is one such agent, which has been extensively used since ages for the treatment of liver conditions, and thus has possibly the greatest patient acceptability. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of silymarin in both in vitro and in vivo animal models of various epithelial cancers. Apart from chemopreventive effects, other noteworthy aspects of silymarin and its active constituent silibinin in cancer treatment include their capability to potentiate the efficacy of known chemotherapeutic drugs, as an inhibitor of multidrug resistance associated proteins, and as an adjunct to the cancer therapeutic drugs due to their organ-protective efficacy specifically liver, and immunostimulatory effects. Widespread use of silymarin for liver health in humans and commercial availability of its formulations with increased bioavailability, further underscore the necessity of carrying out controlled clinical trials with these agents in cancer patients. In this review, we will briefly discuss the outcomes of clinical trials being conducted by us and others in cancer patients to provide insight into the clinical relevance of the observed chemopreventive effects of these agents in various epithelial cancer models.

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Section: Breast Cancermentioning

confidence: 99%

Section: Anticancer and Cancer Preventive Efficacy Of Silymarinmentioning

confidence: 99%

Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

Kaur

Agarwal

2007

Toxicology and Applied Pharmacology

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“…17 However, this inhibition was not observed with oral intake of milk thistle, 16 and no interference with several chemotherapy agents (cisplatin, doxorubicin, vincristine, L-asparaginase) has been shown in preclinical studies at the concentrations used. [26][27][28][29] Several recent studies report no interaction with chemotherapy agents or interference with enzymes involved in metabolism of drugs (CYP3A, CYP1A2, CYP2D6, CYP2Ea, UGT1A1, P-glycoprotein) (reviewed in this issue by Tamayo and Diamond 46 ). These effects may be dose responsive, however, and require further study at higher dosages.…”

Section: Safetymentioning

confidence: 99%

“…In preclinical studies, silymarin appeared to have direct anticancer effects against prostate, breast, and ectocervical tumor cells. 24,25 When the silibinin flavonoid component was tested in vitro, it enhanced the efficacy of cisplatin and doxorubicin against ovarian, breast, and prostate cancer cells [26][27][28] and was synergistic with vincristine, but not L-asparaginase, against CCRF-CEM T cell, acute lymphoblastic leukemia cell lines. 29 When tested in vitro, silibinin did not stimulate growth in several cancer cell lines, including leukemia, colon (Caco-2), and hepatoma (HepG2).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Advances in the Use of Milk Thistle (Silybum marianum)

2007

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Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.

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“…49 However, in vitro research is promising in that it suggests that milk thistle will not decrease efficacy of chemotherapeutic agents, and may even increase effectiveness through synergism. 50 Given the presence of metastatic lesions in the liver, I would discuss the potential risks and benefits of using milk thistle with this client, so that he could make an informed choice about use of this botanical. If the patient is amenable to using milk thistle, I would recommend a dose of 140-200 mg, standardized to contain 70% to 80% silymarin, 3 times daily.…”

Section: Nutrition-related Complementary and Alternative Medicine Neementioning

confidence: 99%

Integrative Tumor Board: Colon Cancer with Liver Metastases

Dixon¹

2003

Integr Cancer Ther

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connected to their implanted ports. They spend the night at home, or, for patients who come to the center from outside of the Chicago area, in a nearby hotel. To use chronotherapy in an outpatient setting entails much behind-the-scenes planning and working out of details, but previous experience has shown that outpatient clinical use of this technology is quite feasible. 3Nurses function collaboratively with physicians in planning and implementing an individualized protocol for each patient. Patient and family teaching is complex, as both the patient and family need to be assured and feel comfortable about being treated with chemotherapy off-site as well as during sleep. Education needs to include basic trouble shooting for minor problems that may occur with the pump. Patients have access to nursing staff during the day and after clinic hours, through the night. Patients are provided with medications for nausea, vomiting, or diarrhea if needed and are educated thoroughly regarding these medications.Other responsibilities for our oncology nurses include research data collection, compliance with regulatory issues, quality assurance, inventory management, and continuing education on managing the technology and programming the pump. Other factors for the oncology nurse to oversee and be aware of are maintenance of the pumps, supplies, and staffing issues, as more nursing time per patient is needed initially when the patient is beginning a regimen of chronomodulated therapy. Documentation of the chemotherapy flow chart, patient assessments, and nursing care plan must be altered as well for this population of patients. Despite the increased work for nurses, a recent pharmacoeconomic analysis showed that the costs of chronotherapy and standard therapy for colon cancer using 5-FU, leucovorin, and oxaliplatin were equivalent: Although chronotherapy cost more to administer, there were fewer toxic reactions and longer time to progression. 4 Chronomodulated chemotherapy has been validated for the improvement of quality of life while undergoing treatment, including less nausea and vomiting, less diarrhea, less asthenia, and less interruption of daily activities. A growing amount of research demonstrates improved treatment outcomes as well. Family support for using chronotherapy is thus usually very strong, especially since the outpatient setting allows family members to feel more involved in the care of their loved one. Patient satisfaction is enhanced also by less need for hospital admissions and increased feeling of well-being. The initial transition to using outpatient chronotherapy did involve substantial alterations to our nursing procedures; once the new routines were incorporated, they proved to be manageable from the nursing and administrative perspectives. Home chronotherapy in our practice has proven to be a safe and acceptable alternative to traditional methods administering chemotherapy, and has provided many of our patients with a vastly improved quality of life as well as the potential for better outcomes. Refe...

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Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin

Cited by 99 publications

References 22 publications

Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

Advances in the Use of Milk Thistle (Silybum marianum)

Integrative Tumor Board: Colon Cancer with Liver Metastases

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