Jasmine George

Resveratrol-based combinatorial strategies for cancer management.

In recent years combination chemoprevention has been increasingly appreciated and investigated as a viable and effective strategy for cancer management. A plethora of evidence suggests that a combination of agents may afford synergistic (or additive) advantage for cancer management by multiple means, such as by (1) enhancing the bio‐availability of chemopreventive agents, (2) modifying different molecular targets, and (3) lowering the effective dose of agent/drug to be used for cancer management. Resveratrol has been shown to afford chemopreventive and therapeutic effects against certain cancers. Recent studies are suggesting that resveratrol may be very useful when given in combination with other agents. The two major advantages of using resveratrol in combination with other agents are synergistically or additively enhancing the efficacy against cancer and limiting the toxicity and side effects of existing therapies. However, concerted and multidisciplinary efforts are needed to identify the most optimal combinatorial strategies.

Mitochondrial Sirtuins in Cancer: Emerging Roles and Therapeutic Potential

The past few decades have witnessed a furious attention of scientific community toward identifying novel molecular factors and targets that could be exploited for drug development for cancer management. One such factor is the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases. The role of SIRTs in cancer is extremely complex, with dichotomous functions depending on cell contexts. Mammalian SIRTs (SIRT1-7) differ in their cellular localization and biologic functions. Among these, SIRT -3, -4, and -5 are located in the mitochondria and are being carefully investigated. These mitochondrial SIRTs (mtSIRT) regulate multiple cellular and physiologic processes, including cell cycle, gene expression, cell viability, stress response, metabolism, and energy homeostasis. Recent research suggests that mtSIRTs influence tumors by regulating the metabolic state of the cell. Although the research on the role of mtSIRTs in cancer is still in its infancy, studies have suggested tumor suppressor as well as tumor promoter roles for them. This review is focused on discussing up-to-date information about the roles and functional relevance of mtSIRTs (SIRT -3, -4, -5) in cancers. We have also provided a critical discussion and our perspective on their dual roles, as tumor promoter versus tumor suppressor, in cancer. Cancer Res; 76(9); 2500-6. ©2016 AACR.

Abstract 3516: The mitochondrial sirtuin SIRT3 promotes survival of human melanoma cells in vitro

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Melanoma, a potentially lethal form of skin cancer, is the fifth most common type of new cancer diagnosis in American men and the sixth most common type in American women. Alarmingly, the annual incidence of melanoma among whites has increased steadily (>60% over the past 30 years). Despite new developments in therapy, the overall survival of patients with advance-stage melanoma has not significantly improved. Therefore, concerted mechanism-based efforts are needed for prevention, diagnosis and treatment of this deadly neoplasm. A better understanding of molecular mechanisms contributing to melanoma development and progression can be useful in crafting new strategies for melanoma management. We are studying the role of sirtuin family of proteins in melanoma development and progression. Mammalian sirtuins (SIRT 1-7) are nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases, which have been shown to regulate metabolism, stress responses, and longevity, in model organisms. The role of sirtuins in cancer is fairly complex with dichotomous functions (tumor promoter versus tumor suppressor) depending on cell contexts. SIRT3 is a mitochondrial deacetylase that has been shown to be important in maintaining cellular metabolism by regulating mitochondrial functions. We have previously shown that SIRT3 was overexpressed in human melanoma cells and tissues and its inhibition resulted in an antiproliferative response in human melanoma cells (In: AACR Annual Meeting: Proceedings; 2013 April 6-April 10, Washington, DC; Abstract # 13-LB-9391). In this study, we found that short hairpin RNA (shRNA)-mediated knockdown of SIRT3 in SK-MEL-28 melanoma cells resulted in 1) G1-phase arrest of cell cycle, 2) induction of senescence as assessed by increase in senescence-associated β-galactosidase (SA-β-gal) activity, 3) senescence associated hetrochromatin formation (SAHF), 4) decrease in cell migration, and 5) increase in protein levels of p53, phospho-p53 (Ser15), p21Waf1, pRb and p16INK4a. Further, a stable exogenous overexpression of SIRT3 resulted in an increase in cell growth and clonogenic survival in Hs 294T melanoma cells. Based on our data we suggest that SIRT3 could be a contributing factor in melanoma survival. However, further extensive in-vitro and in- vivo studies are needed to ascertain the functional significance of SIRT3 in melanoma development and progression. Citation Format: Jasmine George, Minakshi Nihal, Chandra K. Singh, Weixiong Zhong, Nihal Ahmad. The mitochondrial sirtuin SIRT3 promotes survival of human melanoma cells in vitro . [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3516. doi:10.1158/1538-7445.AM2014-3516

Abstract 235: Combination of the probiotic Lactobacillus rhamnosus GG with grape antioxidant resveratrol for the management of colorectal cancer

Colorectal cancer (CRC), also known as colon/bowel cancer, is the third most commonly diagnosed cancer in the world. In the United States, 142,820 new cases of CRC and 50,830 CRC-related deaths are predicted for the year 2013. CRC has been widely associated with lifestyle and aging. Treatment for CRC varies greatly based on disease severity and is curable with surgery, only if detected very early. It is being increasingly appreciated that nutritional and lifestyle modification might prevent or delay certain cancers, including CRC. Imbalance in gut microbiome, due to lifestyle and dietary habits, can lead to a variety of intestinal disorders including excessive immune response and inflammation that might ultimately lead to CRC. The probiotics, which are live microorganisms, have been shown to promote healthy microbiome balance in gut to support healthy colon. For an optimal functioning, the probiotics need to remain viable. This might be achieved via prebiotics and prebiotics-like substances that confer beneficial effects by promoting the microbiota. Therefore, novel means to balance the gut microbiota by prebiotic-probiotic combination could be useful in the management of inflammation related CRC. The grape antioxidant resveratrol (RSV) has been shown to support the health of beneficial gut bacteria, thus functioning essentially as a prebiotic. The goal of this study was to determine if a combination of the resveratrol and the probiotic Lactobacillus rhamnosus GG (LGG) imparts anti-proliferative response in human CRC cell lines, DLD 1 and RKO. For our experiments, DLD1 and RKO cells (∼50% confluent) were treated with RSV and cell free supernatants of LGG. RSV was used at a single concentration (10 µM) whereas LGG cell-free supernatants were used at two concentrations: LGG1 (2.125 x 105 CFU/mL) and LGG2 (4.35 x 105 CFU/mL). We found that a combination of LGG and RSV resulted in a significant decrease in the growth and viability of DLD 1 and RKO cells, as assessed by MTT- and Trypan Blue exclusion- assays. Further, LGG-RSV combination resulted in a marked decrease in the clonogenic survival of CRC cells, as assessed by colony formation abilities of of DLD 1 and RKO cells. Furthermore, LGG-RSV combination resulted in an induction of apoptosis in CRC cells, as determined by cleavage of protein poly (ADP-ribose) polymerase (PARP). Overall, our study provides a proof of principle for the potential use of RSV-LGG combination in CRC management. However, further in vivo studies in appropriate animal model(s) are needed to determine the efficacy of RSV-LGG combination in prevention of CRC. Citation Format: Chandra K. Singh, Jasmine George, Megan Duster, Nasia Safdar, Nihal Ahmad. Combination of the probiotic Lactobacillus rhamnosus GG with grape antioxidant resveratrol for the management of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 235. doi:10.1158/1538-7445.AM2014-235

Abstract 3667: Potential role of DUSP4 as a tumor suppressor in pancreatic cancer

Pancreatic cancer remains one of the most lethal of all human malignancies, with 48,960 expected new cases and 40,560 deaths predicted in the USA in the year 2015. In order to develop novel strategies for the management of pancreatic cancer, it is of utmost importance to intensify our efforts to dissect the molecular mechanisms involved in the pathophysiology of this fatal neoplasm. Dual-specificity phosphatase-4 (DUSP4), a family member of dual-specificity phosphatases, is capable of dephosphorylating both phosphotyrosine and phosphoserine/phosphothreonine residues and possesses activity against key signaling components of the MAPK pathway that plays an important role in cancer growth. DUSP4 has been shown to be widely expressed in different tissues and implicated in cancer development, differentiation, apoptosis and inflammation. In a recent study from our laboratory that was aimed at defining the molecular targets of the anti-cancer plant-based alkaloid sanguinarine in pancreatic cancer, we identified DUSP4 as a key protein modulated by sanguinarine. Specifically, based on proteomics data and validation by qRT-PCR and immunoblot analysis, we found that sanguinarine significantly increases DUSP4 in BxPC-3 and MIA PaCa-2 pancreatic cancer cells. Indeed, an association of DUSP4 loss with cancer progression has been shown in certain cancers. However, the role of DUSP4 in pancreatic cancer is not known. This study was designed to determine the role and importance of DUSP4 in pancreatic cancer. We determined the expression profile of DUSP4 in pancreatic cancer using immunohistochemical analysis of a tissue microarray containing a variety of pancreatic cancers and normal pancreatic tissues. The DUSP4-immunostaining was microscopically imaged followed by quantification of DUSP4 protein by multispectral Vectra™ system coupled with inForm software. We found a significant downregulation of DUSP4 in human pancreatic cancer tissues, when compared to normal pancreatic tissues. Further, to understand the importance of DUSP4 in pancreatic cancer, we determined the effect of a force overexpression of DUSP4 in MIA PaCa-2 pancreatic cancer cells. We found that DUSP4 overexpression in MIA PaCa-2 cells resulted in a significant i) decrease in cell growth and proliferation, ii) clonogenic survival, and iii) induction of apoptosis. These preliminary findings suggest a potential tumor suppressive function of DUSP4 in pancreatic cancer. Further detailed studies are ongoing in our laboratory to validate the role and functional significance of DUSP4 in pancreatic cancer. Citation Format: Chandra K. Singh, Jasmine George, Minakshi Nihal, Nihal Ahmad. Potential role of DUSP4 as a tumor suppressor in pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3667.

Abstract 1143: Pro-proliferative function of SIRT3 in a human melanoma xenograft mouse model

Melanoma is one of the most aggressive forms of skin cancer and is often lethal, if not treated early. Therefore, it is necessary to try to develop novel target-based strategies to combat this neoplasm. SIRT3 is a nicotinamide adenine dinucleotide (NAD+) -dependent mitochondrial protein deacetylase involved in metabolism- and aging- related disorders, including certain cancers. Interestingly, studies have suggested both tumor suppressor as well as tumor promoter roles of SIRT3 in cancer. However, its role in melanoma is not well-established. Previously, we have shown that SIRT3 was upregulated in human melanoma cells and its lentiviral knockdown resulted in anti-proliferative effects in human melanoma cells. We also found that SIRT3 knockdown resulted in the G1-phase arrest of the cell cycle, induction of senescence, and decrease in cell migration. This study was designed to determine the relevance of our in vitro findings to the in vivo situation, in human melanoma xenograft models. Employing immunodeficient mice (Crl:NU-Foxn1nu, homozygous; Strain 088), we first determined the effect of SIRT3-knockdown on melanoma tumorigenesis. The mice were subcutaneously implanted with shNS-SK-MEL-2 (control) and shSIRT3-SK-MEL-2 (SIRT3-knockdown) melanoma cells, followed by assessing tumorigenesis of melanoma cells. We found that compared to shNS-SK-MEL-2 cells, shSIRT3-SK-MEL-2 cells showed a significantly decreased tumorigenic potential in these mice, in terms of average tumor volume (measured weekly) and average tumor weight (measured at termination of the study). Further, the Kaplan-Meier analysis showed that SIRT3 knockdown resulted in a significant survival advantage, in terms of reaching the cutoff tumor size (2.0 cm in one dimension). In an additional strategy, we determined the tumorigenicity of SIRT3 overexpressing melanoma cells (Hs294T-SIRT3) in NU/NU mice. Our data demonstrated that compared to control Hs294T-pcDNA cells, the SIRT3 overexpressing Hs294T-SIRT3 cells demonstrated a significantly enhanced tumorigenic potential (average tumor volume and tumor weight) in NU/NU mice. Overall, our study provides evidence supporting a pro-proliferative role of SIRT3 in melanoma and suggests that SIRT3 needs to be further evaluated as a potential druggable therapeutic target for melanoma management. However, detailed mechanistic and in vivo studies in relevant melanoma models are needed to further validate our findings. Citation Format: Jasmine George, Minakshi Nihal, Mary A. Ndiaye, Nihal Ahmad. Pro-proliferative function of SIRT3 in a human melanoma xenograft mouse model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1143.

Abstract 1127: Small molecule SIRT3 inhibitor 4′-bromo-resveratrol inhibits proliferation, promotes apoptosis and causes metabolic reprograming of human melanoma cells

Sirtuin-3 (SIRT3) is an important mitochondria NAD+-dependent deacetylase that is known to target mitochondrial proteins for deacetylation and regulates a variety of cellular functions. We have previously shown that SIRT3 was overexpressed in human melanoma cells and tissues and its genetic knockdown resulted in a significant antiproliferative response in human melanoma cells (In: AACR Annual Meeting: Proceedings; 2014 April 5-April 9, San Diego; CA, Abstract # 3516). Our data suggested that small molecule inhibitors of SIRT3 may be developed for the management of melanoma. In this study, we determined the anti-proliferative efficacy of a newly identified small molecule SIRT3 inhibitor, 4′-bromo-resveratrol, in human melanoma cell lines (G361, SK-MEL-28 and SK-MEL-2). Treatment of melanoma cells with 4-bromoresveratrol (0, 12.5, 25, 50, 100, and 200 × 10-3 mM; for 24, 48 and 72 hrs) resulted in a significant decrease in cell proliferation in a dose- and time- dependent manner. In addition, 4′-bromo-resveratrol treatment also resulted in a marked decrease in the growth, viability, clonogenic survival and migration of melanoma cells. Further, the anti-proliferative effects of 4′-bromo-resveratrol were accompanied by a marked downregulation of proliferating cell nuclear antigen (PCNA) protein as well as SIRT3 mRNA and protein. Furthermore, 4′-bromo-resveratrol treatment to melanoma cells resulted in 1) significant induction of apoptosis in melanoma cells, as evident from increase in PARP cleavage, decrease in pro-caspase-3, pro-caspase-8; and 2) G0/G1 phase cell cycle arrest. We also observed a marked increase in WAF-1/p21 protein levels and decreases in cyclin D1 and cdk2 protein levels as a result of 4′-bromo-resveratrol treatment in melanoma cells. Finally, we also found that 4′-bromo-resveratrol caused a metabolic reprograming in human melanoma cells as shown by decreases in the levels of lactate production, glucose uptake, NAD+/NADH ratio, which were accompanied by downregulation in protein levels of lactate dehydrogenase A (LDHA) and glucose transporter 1 (Glut1) in melanoma cells. Collectively, our data suggest that the small molecule SIRT3 inhibitors, including 4′-bromo-resveratrol, may be developed for melanoma management. However, detailed mechanistic studies as well as in vivo validation studies in appropriate animal model(s) are needed to ascertain the clinical potential of 4′-bromo-resveratrol and/or other SIRT3 inhibitors. Citation Format: Jasmine George, Minakshi Nihal, Chandra K. Singh, Nihal Ahmad. Small molecule SIRT3 inhibitor 4′-bromo-resveratrol inhibits proliferation, promotes apoptosis and causes metabolic reprograming of human melanoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1127. doi:10.1158/1538-7445.AM2015-1127

Abstract 4643: Effect of resveratrol-zinc combination on prostate tumor growth in transgenic adenocarcinoma of mouse prostate (TRAMP) model

Prostate cancer (PCa) is a major cancer of males globally and is associated with significant mortality and morbidity across the globe. The trace element zinc (Zn) plays a critical role in a variety of prostatic functions and normal prostate accumulates Zn at up to ten-fold higher concentration than other soft tissues in the body. However, the cancerous prostate lose the ability to accumulate Zn and lower levels of prostatic Zn has been associated with development and progression of PCa. Studies have suggested that a dysregulation in the transport machinery of Zn, possibly mediated via ZIP and ZnT families of Zn transporters, may be associated with this neoplastic transformation of prostate. Thus, re-tuning of Zn transport machinery via pharmacological means could be useful in PCa management. We have previously demonstrated that the grape antioxidant resveratrol (RSV) enhances the anti-proliferative response of Zn by increasing Zn-transporter protein ZIP1 in prostate cancer cells in vitro (Cancer Res 2012; 72(8 Suppl): Abstract nr 3729. doi: 1538-7445.AM2012-3729). Here, we extended our study to determine the in vivo relevance of our in vitro findings. We assessed the effect of RSV (600 mg/kg in diet) in combination with Zn (15 and 30 ppm ZnSO4.7H2O in drinking water) against prostate cancer progression in TRAMP mice, employing two experimental protocols, which represent prevention and intervention settings, respectively. We found that RSV-Zn combination, when given prior to tumor initiation (4 weeks of age), showed superior anti-tumor efficacy than either of the agents alone. However, we did not find a significant anti-tumor response of RSV and/or Zn in the intervention protocol. We also determined the effect of RSV and/or treatments on markers of proliferation and apoptosis in tumor tissues obtained from TRAMP mice. Interestingly, we found that lower dose of Zn (15 ppm) was most consistent in imparting anti-proliferative response; resulting in a significant i) decrease in tumor weight/volume, ii) decrease in proliferative marker PCNA, iii) increase of pro-apoptotic Bax, and iv) decrease of the pro-survival Bcl2. In addition, the observed response of RSV-Zn combination was associated with an increase in ZIP4 protein. Further experiments are ongoing to dissect the mechanism of the PCa chemoprevention effects of RSV-Zn combination. Outcome of this study may provide a foundation for the use of RSV-Zn combination for PCa management. Citation Format: Chandra K. Singh, Minakshi Nihal, Jasmine George, Imtiaz A. Siddiqui, Hasan Mukhtar, Nihal Ahmad. Effect of resveratrol-zinc combination on prostate tumor growth in transgenic adenocarcinoma of mouse prostate (TRAMP) model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4643. doi:10.1158/1538-7445.AM2015-4643

Abstract 4533: Mechanism of anti-proliferative effects of sanguinarine in pancreatic cancer cells: A label-free quantitative proteomics approach

Pancreatic cancer is one of the most lethal cancers, with a meager (∼3%) 5-year survival rate. The incidence of pancreatic cancer nearly equals its death rate as this neoplasm is associated with poor responsiveness to conventional chemotherapies. Therefore, its crucial to identify newer mechanism-based agents and targets to effectively manage pancreatic cancer. Previous studies from our laboratory have demonstrated that the plant alkaloid sanguinarine (13-methyl(1,3)benzodioxolo (5,6-c)-1,3-dioxolo (4,5-i) phenanthridinium possesses strong antiproliferative effects against human pancreatic carcinoma cells (Cancer Letters 249; 198-208, 2007). In this study, employing a large-scale Nano-ESI ultra high resolution label-free quantitative proteomics, we attempted to determine the mechanism of sanguinarines biological response in human pancreatic cancer cells. Based on pilot experiments, we selected BxPC-3 cells and a 1 microM sanguinarine treatment for 24 hours for our proteomics study. Proteins from control and sanguinarine-treated BxPC-3 cells were digested with trypsin followed by nano-liquid chromatography-tandem mass spectrometry (LC/MS/MS). Following LC/MS/MS acquisition, the data were searched against the Swiss-Prot human proteome database using Sequest HT search engine under the Proteome Discoverer 1.4 software (Thermo Fisher Scientific). Following protein identification, the LC/MS/MS data was aligned using Chromalign and quantitation of peptides was performed on the processed data using Sieve 2.1 (Thermo Fisher Scientific). A cumulative data of a total of 6 replicates (2 biological and 3 technical) were run and analyzed. Upon comparison with untreated control, 37 proteins (from a total of 3108) showed +1.8 fold significant differential expressions (p value <0.05). These proteins can be categorized under distinct biological functions: 1) cellular assembly and organization, 2) cellular function and maintenance, 3) inflammatory response, and 4) cell death and survival. On further data analysis and validation using real-time qPCR and Western blot analyses, we identified the dual specificity phosphatase-4 (DUSP4), as a novel target of sanguinarine in pancreatic cancer cells. In order to determine the clinical relevance of DUSP4 in pancreatic cancer cells, we determined the expression profile of DUSP4 in a tissue microarray (TMA) containing a wide range of pancreatic cancer tissue (different stages) and normal pancreas tissue from autopsy. We found that that DUSP4 is markedly downregulated in cancerous pancreatic tissues. Our data identified, for the first time, DUPS4 as a potential tumor suppressor in pancreatic cancer and a novel target of sanguinarine. However, further studies are needed to validate our findings in detailed in vitro and in vivo studies.

Abstract LB-209: SIRT3, a mitochondrial sirtuin deacetylase, promotes survival of human melanoma cells.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Melanoma is one of the most aggressive skin cancers and is often lethal, if not diagnosed early. The existing therapeutic approaches as well as preventive strategies have not been able to effectively manage melanoma. A better understanding of mechanisms of melanoma development and progression may lead to additional means for the management of this deadly neoplasm. Sirtuins are NAD+-dependent protein deacetylases and mono-[ADP-ribosyl]transferases, which have been shown to regulate metabolism, stress responses, and longevity, in model organisms. Mammalian sirtuins, also referred to as class III histone deacetylases, have seven members (SIRT1-7) that differ widely in their localization, activity, and functions. The role of sirtuins in cancer is extremely complex and they have been shown to exhibit dichotomous functions (tumor promoter versus tumor suppressor) depending on cell contexts. SIRT3 is a mitochondrial deacetylase that regulates the activity of enzymes to coordinate global shifts in cellular metabolism. While studies have suggested that the SIRT3 acts as a tumor suppressor in some cancers (such as breast cancer), the tumor promoter function of SIRT3 has also been reported in other cancers (such as oral squamous cell carcinoma). The objective of this study was to determine the role of the SIRT3 in melanoma. Employing a panel of human melanoma cell lines (SK-MEL-28, WM35 and G361) and normal human epidermal melanocytes (NHEMs), we determined the endogenous levels of SIRT3. We found that compared to NHEMs, SIRT3 is significantly upregulated in human melanoma cells, at mRNA as well as protein levels, as shown by quantitative Real-Time PCR and Western blot analysis, respectively. Further, employing a tissue microarray (TMA) analysis, we determined the expression profile of SIRT3 protein in clinical melanoma and normal skin tissues. We found that SIRT3 is overexpressed in human melanoma, when compared to normal skin. Further, we determined the effect of a short hairpin RNA (shRNA)-mediated RNA interference on melanoma cells. Our data demonstrated that shRNA knockdown of SIRT3 resulted in a significant decrease in the growth, viability and clonogenic survival of human melanoma cells. Taken together, our data suggested that i) SIRT3 overexpression could be a contributing factor in melanoma survival, and ii) SIRT3 could serve as a potential target towards developing novel strategies for the management of melanoma. However, further in-depth studies are needed to determine the functional significance of SIRT3 overexpression in melanoma development and progression. Citation Format: Jasmine George, Minakshi Nihal, Chandra K. Singh, Nihal Ahmad. SIRT3, a mitochondrial sirtuin deacetylase, promotes survival of human melanoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-209. doi:10.1158/1538-7445.AM2013-LB-209