Lupeol Inhibits Growth of Highly Aggressive Human Metastatic Melanoma Cells <i>In vitro</i> and <i>In vivo</i> by Inducing Apoptosis

Saleem, Mohammad; Maddodi, Nityanand; Zaid, Mohammad Abu; Khan, Naghma; Hafeez, Bilal Bin; Asim, Mohammad; Suh, Yewseok; Yun, Jung‐Mi; Setaluri, Vijayasaradhi; Mukhtar, Hasan

doi:10.1158/1078-0432.ccr-07-4413

Cited by 130 publications

(105 citation statements)

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“…The results of the present study suggest that surgery combined with lupeol administration achieves local tumor control equivalent to that of radiation therapy. Saleem et al (13) reported that lupeol inhibits the growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. The results of the present study suggest that, in addition to preventing local progression, systemic postoperative adjuvant lupeol administration may also prevent the development of distant tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies reported that lupeol has antitumor properties (11,12) and several reports indicated that lupeol inhibits melanoma cell proliferation in vitro and in vivo (13,14). Recently, Nitta et al (14) reported that systemic lupeol administration inhibited tumor growth in a melanoma-bearing mouse model; however, there is no report evaluating its clinical efficacy in COMM.…”

Section: Introductionmentioning

confidence: 99%

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Clinical systemic lupeol administration for canine oral malignant melanoma

Yokoe¹,

Aso²,

Hata³

et al. 2014

Molecular and Clinical Oncology

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Abstract. Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperatively at various time points to treat these 11 COMM cases. Of the 11 subjects, 7 exhibited no local recurrence 180 days postoperatively and no severe adverse effects were observed in any of the cases. Furthermore, no distant metastasis was observed during the experimental period. Therefore, systemic lupeol may prevent local tumor progression and distant metastasis and may be a novel adjuvant treatment for the treatment of COMM. IntroductionCanine oral malignant melanoma (COMM) is the most common malignancy in dogs, accounting for 30-40% of all oral tumors (1,2). COMM is characterized by extensive local invasion, as well as distant metastasis (2). Melanoma treatment includes radiation therapy and chemotherapy (CT), either alone, as an adjuvant therapy following surgery, or in combination (2). Although radiation therapy provides effective local tumor control, it is only performed in selected facilities (3-5).In addition, radiation therapy may be costly and, hence, beyond the financial means of some owners. Several reports have investigated the efficacy of CT in COMM, but there is no definitive evidence regarding its effectiveness (5,6,7-9). Therefore, there is a need for an alternative treatment for COMM.Lupeol is a triterpene found in fruits such as olives, mangoes, strawberries, grapes and figs, numerous vegetables and several medicinal plants (10). Previous studies reported that lupeol has antitumor properties (11,12) and several reports indicated that lupeol inhibits melanoma cell proliferation in vitro and in vivo (13,14). Recently, Nitta et al (14) reported that systemic lupeol administration inhibited tumor growth in a melanoma-bearing mouse model; however, there is no report evaluating its clinical efficacy in COMM. In this study, we aimed to evaluate the efficacy of subcutaneous lupeol as an adjuvant therapy for spontaneous COMM. Subjects and methods Subjects.A total of 11 dogs were included in this study. The characteristics of the sublects are summarized in Table I. The represented breeds included 2 miniature Dachshunds, 2 Beagles, 2 miniature Schnauzers, 1 Golden Retriever, 1 Labrador Retriever, 1 American Cocker Spaniel, 1 Cavalier King Charles Spaniel and 1 mixed-breed dog. The dogs ranged in age between 8 and 17 years. The tumors in all 11 dogs were classified according to the TNM classification (1,2) as follows: 3 dogs had stage I, 5 dogs had stage II and 3 dogs had stage III disease (Table I). Two cases of cancer recurrence were included (C04 and C07). This study was conducted between April, 2010 and M...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical systemic lupeol administration for canine oral malignant melanoma

Yokoe¹,

Aso²,

Hata³

et al. 2014

Molecular and Clinical Oncology

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“…Interestingly, lupeol was shown to significantly suppress androgen analog R1881-induced transcriptional activity of AR and expression of PSA. Lupeol blocked the binding of AR to AR-responsive genes, including PSA, TIPARP, SGK, and IL-6, and inhibited the recruitment of RNA Pol II to target genes [139] and also significantly decreased the transcriptional activation of survivin and cFLIP genes and b-catenin signaling in prostate and metastatic melanoma cells [140][141][142]. Lupeol treatment in melanoma cells resulted in a dose-dependent decrease in cell viability, induction of apoptosis, suppressed colonogenic potential, and reduced b-catenin transcriptional activity and the expression of Wnt target genes [143].…”

Section: Lupeolmentioning

confidence: 97%

Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer

et al. 2012

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a b s t r a c tOver the last two decades, extensive research on plant-based medicinal compounds has revealed exciting and important pharmacological properties and activities of triterpenoids. Fruits, vegetables, cereals, pulses, herbs and medicinal plants are all considered to be biological sources of these triterpenoids, which have attracted great attention especially for their potent anti-inflammatory and anti-cancer activities. Published reports in the past have described the molecular mechanism(s) underlying the various biological activities of triterpenoids which range from inhibition of acute and chronic inflammation, inhibition of tumor cell proliferation, induction of apoptosis, suppression of angiogenesis and metastasis. However systematic analysis of various pharmacological properties of these important classes of compounds has not been done. In this review, we describe in detail the pre-clinical chemopreventive and therapeutic properties of selected triterpenoids that inhibit multiple intracellular signaling molecules and transcription factors involved in the initiation, progression and promotion of various cancers. Molecular targets modulated by these triterpenoids comprise, cytokines, chemokines, reactive oxygen intermediates, oncogenes, inflammatory enzymes such as COX-2, 5-LOX and MMPs, anti-apoptotic proteins, transcription factors such as NF-jB, STAT3, AP-1, CREB, and Nrf2 (nuclear factor erythroid 2-related factor) that regulate tumor cell proliferation, transformation, survival, invasion, angiogenesis, metastasis, chemoresistance and radioresistance. Finally, this review also analyzes the potential role of novel synthetic triterpenoids identified recently which mimic natural triterpenoids in physical and chemical properties and are moving rapidly from bench to bedside research.

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“…Lupeol was also observed to inhibit ODC activity, an important biomarker of tumor promotion [103,118]. Lupeol was also shown to inhibit growth of highly metastatic tumors of human melanoma origin by modulating the expression of BCl-2 and Bax proteins [104]. A recent study demonstrated that lupeol significantly inhibits the growth of metastatic melanoma cells that harbor constitutive activation of Wnt/ -catenin signaling [119].…”

Section: Lupeolmentioning

confidence: 99%

“…Lupeol has been demonstrated to inhibit various pharmacological activities under in vitro and in vivo conditions. These include its beneficial activity against inflammation, cancer, arthritis, diabetes, heart disease, renal-and hepatic toxicity [94,[98][99][100][101][102][103][104][105][106][107]. Topical application of lupeol alleviated TPA-induced inflammation in the ear mouse model [98] and decreased the expression of myeloperoxidase, a neutrophil specific marker, resulting in reduced infiltration into inflamed tissues [98].…”

Section: Lupeolmentioning

confidence: 99%