Sonam Kumari

Curcumin Nanoformulation for Cervical Cancer Treatment

Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear β-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer.

Slit/Robo pathway: a promising therapeutic target for cancer

Axon guidance molecules, slit glycoprotein (Slit) and Roundabout receptor (Robo), have implications in the regulation of physiological processes. Recent studies indicate that Slit and Robo also have important roles in tumorigenesis, cancer progression and metastasis. The Slit/Robo pathway can be considered a master regulator for multiple oncogenic signaling pathways. Herein, we provide a comprehensive review on the role of these molecules and their associated signaling pathways in cancer progression and metastasis. Overall, the current available data suggest that the Slit/Robo pathway could be a promising target for development of anticancer drugs.

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells—all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13–HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13–HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13–HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC.

MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer

Pancreatic tumors are rewired for high-glucose metabolism and typically present with exceptionally poor prognosis. Recently, we have shown that MUC13, which is highly expressed in pancreatic tumors, promotes tumor progression via modulation of HER2 receptor tyrosine kinase activity. Herein, we investigate a novel, MUC13-mediated molecular mechanism responsible for higher glucose metabolism in pancreatic tumors. Our results demonstrate that MUC13 expression leads to the activation/nuclear translocation of NF-κB p65 and phosphorylation of IκB, which in turn upregulates the expression of important proteins (Glut-1, c-Myc, and Bcl-2) that are involved in glucose metabolism. MUC13 functionally interacts and stabilizes Glut-1 to instigate downstream events responsible for higher glucose uptake in pancreatic cancer cells. Altered MUC13 expression by overexpression and knockdown techniques effectively modulated glucose uptake, lactate secretion, and metastatic phenotypes in pancreatic cancer cells. NF-κB inhibitor, Sulfasalazine, abrogates the MUC13 and Glut-1 interaction, and attenuates events associated with MUC13-induced glucose metabolism. Pancreatic ductal adenocarcinoma (PDAC) patient tissue samples also show a positive correlation between the expression of these two proteins. These results delineate how MUC13 rewire aberrant glucose metabolism to enhance aggressiveness of pancreatic cancer and revealed a novel mechanism to develop newer therapeutic strategies for this exceptionally difficult cancer.

Abstract 51: Role of MUC13 as non-hypoxic stimuli inducing HIF-1α in pancreatic cancer under normoxia

Objective: Pancreatic cancer is the fourth most common cause of deaths occurring due to cancer, with an overall survival rate of just 5%. MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic cancer, while an altered glucose metabolism is known to facilitate cancer cell survival and proliferation. Hypoxia-inducible factor 1 α (HIF-1 α) plays an important role in reprogramming of cancer cell metabolism by activating the transcription of genes which encode glucose transporters and enzymes involved in glycolysis. Recent reports suggest that several non-hypoxic stimuli such as lipopolysaccharides, thrombin, and angiotensin II can also increase HIF-1α under normoxia. Herein, we investigated the effects of MUC13 expression on glucose metabolism and elucidated underlying signaling mechanisms that might be involved in this process. Methods: MUC13 null pancreatic cancer Panc-1 cells were used for the study. Glucose and Lactate assay were performed in Panc-1 cells stably expressing MUC13 (Panc-1-M13) and vector (Panc-1-V). Cell culture media after 48 hrs was collected to measure the amount of unused glucose and L-lactate concentration using glucose and Lactate assay kits. Immunoblot and semi-quantitative PCR analyses were performed to check the expression of protein and mRNA levels, respectively. Cell proliferation and colony forming assays were performed to determine the effect of MUC13 on cellular growth and cell survival. Results: Our results demonstrate that MUC13 acts as a modulator of the glucose metabolism in pancreatic cancer cells by regulating the expression and activity of hypoxia-inducible factor-1α (HIF-1α) and its downstream targets. We observed increased amount of L-lactate production and glucose consumption in Panc-1-M13 cells as compared to Panc-1-V cells. This facilitates metabolic alterations and help tumor cells survive and proliferate under these conditions as indicated by increased cellular growth pattern in Panc-1-M13 cells. Our results demonstrate increased expression of the downstream targets of HIF-1α, such as cell regulatory (c-Myc), and cell survival (Bcl-2) proteins, while decreased the expression of tumor suppressor/cell cycle inhibitor (p-27) proteins in Panc-1M13 cells. Additionally, an increase in the expression of a critical downstream target of HIF-1α, Glut-1 was observed in Panc-1-M13 cells. Conclusion: Our studies indicate that MUC13 acts as a key regulator of the metabolic process and facilitates metabolic alterations in the non-hypoxic environment that help tumor cells survive and proliferate under these conditions. However, further studies are required to elucidate detailed molecular mechanisms that are involved in MUC13 mediated metabolic remodeling in pancreatic cancer cells. Citation Format: Sonam Kumari, Sheema Khan, Subhash Chauhan, Meena Jaggi. Role of MUC13 as non-hypoxic stimuli inducing HIF-1α in pancreatic cancer under normoxia. [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 51.

Abstract 182: Smoking Carcinogen (BaP) enhances tumorigenic phenotypes of cervical cancer cells by modulation of HPV oncogenes and microRNA profiles

Cervical cancer (CxCa), one of the most common and deadly cancers among women worldwide, is associated with persistent Human Papillomavirus (HPV) infection. An importunate oncogenic HPV infection itself is not enough to immortalize and transform the epithelial host cell. Additional factors are needed to acquire an immortal, malignant and invasive phenotype. In addition to HPV infection, cigarette smoking is a known risk factor. Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, is among the numerous carcinogens associated with cigarette smoking. BaP levels have been found to be elevated in the cervical mucus of women who smoke. BaP has been shown to stimulate high levels of the viral oncoproteins E6 and E7 besides enhancing virion synthesis in cell lines prolifically infected with HPV. Furthermore, mixtures containing BaP, such as cigarette smoke condensate, have been shown to induce dramatic microRNA (miR) alterations in rodent lungs and in vitro human bronchial models. MiRs, small non-coding RNAs, regulate gene expression and their aberrant regulation/function has been reported in a large majority of cancers. Additionally, previous studies have shown the role of BaP in modulating miR profiles in different cancers. In this study we examine the effects of the carcinogen BaP on miRs and their related pathways in CxCa. In vitro treatment of CxCa cells with BaP resulted in an increase of expression of oncogenic miR-21 and decrease in tumor suppressor miR-214. MiR-21 has been shown to enhance chemoresistance to established regimens of chemotherapy and radiation therapy. In addition BaP also modulates the downstream pathways that these miRs regulate. BaP treatment increased the expression of oncogenic transcription factors such as NFkB-65, pSTAT-3, pSTAT-5 (transcription factors promoting miR-21 expression) and oncogenic cytokine IL-6, besides decreasing tumor suppressor PTEN (a target of miR-21). IL-6 is known to increase miR-21 expression through pSTAT-3 and pSTAT-5. Moreover, BaP in combination with IL-6 enhanced the migratory properties of CxCa cells. BaP also increased the nuclear translocation of β-catenin as observed through confocal microscopy. β-catenin is a direct target of miR-214. Natural or synthetic compounds that can mitigate BaP induced tumorigenic effects can have tremendous clinical significance. Herein, we report that curcumin (C) or its PLGA (poly [lactic-co-glycolic acid]) based nanoformulation (NC) effectively suppresses BaP induced tumorigenicity, regulates the expression of miRs and nuclear translocation of β-catenin associated with BaP in Caski/SiHa CxCa cells. In vivo experiments show that C/NC efficaciously reduced the tumor burden in xenograft mouse model. These data suggest a potential role of smoking in CxCa progression via regulating miR profiles and C/NC may effectively attenuate smoking induced CxCa progression. Citation Format: Mohd Saif Zaman, Neeraj Chauhan, Rishi K. Gara, Diane Maher, Sonam Kumari, Mohammed Sikander, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan. Smoking Carcinogen (BaP) enhances tumorigenic phenotypes of cervical cancer cells by modulation of HPV oncogenes and microRNA profiles. [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 182. doi:10.1158/1538-7445.AM2015-182

Abstract 3676: Attenuation of pancreatic cancer stemness and growth by a novel magnetic nanoparticle formulation

Background: Pancreatic cancer (PanCa) is one of the deadliest cancers accounting for high mortality rates due to high desmoplasia and the development of chemo-resistance to chemotherapeutic drugs, such as gemcitabine (GEM). Curcumin (CUR) has showed potent anticancer, chemopreventive, chemo-sensitization properties and has entered phase II clinical trials in pancreatic adenocarcinoma patients. However, the clinical translation of CUR has been significantly hampered due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. To address these clinically relevant issues, we have successfully engineered a magnetic nanoparticle formulation of curcumin (MNP-CUR) using a multi-layer approach, for its efficient and tumor targeted delivery. Methods: Western blotting and qPCR were used to investigate the effects of MNP-CUR, GEM and their combination on Hh signaling pathway and related proteins involved in PanCa. The antitumor effects were studied using PanCa xenograft mice. Tumor tissue sections were stained for SHH (sonic hedgehog) and its effector (Gli-1), cygb/STAP (stellate cell selective markers) α-SMA (PSC activation), F4/80 (macrophage) for imunohistochemistry/immunofluorescence and microRNAs through in situ hybridization. Results: MNP-CUR alone or in combination with GEM inhibits pluripotency maintaining factors (Nanog, Sox-2, c-Myc and Oct-4) in human pancreatic cancer stem cells thereby, restricts the formation of secondary mamospheres. Further investigations reveal that MNP-CUR inhibits Panca proliferation, migration, invasion and tumor growth in xenograft mouse model by suppression of the sonic hedgehog (SHH) signaling pathway and CXCR4/CXCL12 signaling axis that inhibit bidirectional tumor-stromal cells interaction. MNP-CUR treatment alone or in combination with CXCR4 antagonist (amd3100) inhibits CXCL12 induced up regulation of CXCR4, SHH and NFĸB-65 in cells. Further, qRT-PCR results showed that MNP-CUR treatment increases GEM sensitivity by up regulating the human nucleoside transporter genes (hENT, hCNT) and blocking ribonucletide reductase subunits (RRM1/RRM2) which further supports the use of MNP-CUR for suppression of PanCa growth. Immunostaining of tumor sections from treated pancreatic xenograft mice revealed that MNP-CUR treatment efficiently inhibits key proteins of SHH signaling such as SHH and Gli-1. MNP-CUR also disrupts the stroma of fibrotic pancreatic tumors by inhibiting proliferating stellate and myeloid cells. This was indicated by the decreased staining of αSMA, macrophages and cygb/STAP in tumor tissues. Additionally, the tumor tissues from MNP-CUR treated mice showed extensive downregulation of oncogenic miR-21 expression which has been associated with cancer progression and drug resistance. Conclusion: These data suggest that MNP-CUR possesses great promise as a treatment of choice for PanCa. Citation Format: Sheema Khan, Murali M. Yallapu, Sonam Kumari, Aditya Ganju, Swathi Balakrishna, Stephen W. Behrman, Nadeem Zafar, Meena Jaggi, Subhash C. Chauhan. Attenuation of pancreatic cancer stemness and growth by a novel magnetic nanoparticle formulation. [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 3676. doi:10.1158/1538-7445.AM2015-3676

Abstract 2072: Ormeloxifene attenuates wnt/β-catenin signaling in colon cancer cells by modulation of PKD1 and glycolytic pathways

Background: Colorectal cancer is the third most commonly diagnosed cancer and third leading cause of cancer-related deaths. Aberrant Wnt/β-catenin signaling is implicated in development and progression of colon cancers. Therefore, modulation of this master regulatory signaling is essential for the prevention and treatment of colon cancer. Protein Kinase D1 (PKD1) which is downregulated in colon cancer, regulates β-catenin transcriptional activity by its phosphorylation. Therefore, drug mediated upregulation of PKD1 may have high clinical significance for the prevention/treatment of Wnt/β-catenin signaling induced cancers. We have identified, ormeloxifene, a synthetic non-steroidal selective estrogen receptor modulator (SERM), as a novel PKD1 modulator. Herein, we have investigated the effect of ormeloxifene on tumorigenic phenotypes of colon cancer cells and its effect on PKD1 and glycolytic pathways mediated oncogenic β-catenin signaling. Materials and Methods: We have used SW480-PKD1-GFP and SW480-GFP colon cancer cells (SW480 has a mutated APC gene leading to stabilization of β-catenin due to lack of degradation) to investigate the effect of PKD1 on β-catenin activity and xenograft mouse model. SW480, SW48, SW620 and Lovo cell lines have been used to observe the effect of ormeloxifene (5-20 μM) on various cellular characteristics, including cell proliferation, clonogenic potential, motility and aggregation. β-catenin/T-cell factor 4 (TCF4) transcription activity was measured by Dual-Glo luciferase reporter assays. The expression and subcellular localization of proteins was determined by immunoblotting and confocal microscopy. Chemokine (C-C) motif ligand 2 (CCL2) and glucose assay were performed using ELISA technique. Results: Ormeloxifene treatment restores PKD1 expression, thereby, attenuates β-catenin transcriptional activity. We have also observed that ormeloxifene treatment effectively inhibits CCL2 expression, glucose uptake, glucose metabolism and Glut1 receptor expression in cancer cells. Ormeloxifene (5-20μM) inhibits cell proliferation and motility of colon cancer cells. Additionally, ormeloxifene effectively inhibited CCL2 mediated cellular migration of colon cancer cells. Furthermore, Western blot results depict that PKD1 inhibits TCF4 activity in colon cancer cells. SW480 PKD1 overexpressing cells clearly delayed tumor formation in nude mice, compared to control cells. In addition, SW480-PKD1-GFP cells showed less hypoxia (Glut1) and increased Vasculature (CD31) in tumors. Conclusion: Our findings demonstrate that ormeloxifene treatment effectively attenuates β-catenin mediated oncogenic signaling and tumorigenic phenotypes of colon cancer cells via upregulation of PKD1 and suppression of glycolytic pathways. Thus it can be used as a potential new preventive/treatment modality for colon cancer. Citation Format: Aditya Ganju, Rishi Gara, Sonam Kumari, Man Mohan Singh, Subhash Chauhan, Meena Jaggi. Ormeloxifene attenuates wnt/β-catenin signaling in colon cancer cells by modulation of PKD1 and glycolytic pathways. [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 2072. doi:10.1158/1538-7445.AM2015-2072

Abstract 1001: Protein Kinase D1 induces autophagic cell death through activation of endoplasmic reticulum stress in prostate cancer cells

Background: Advanced stage of prostate cancer is difficult to treat and manage. Autophagy facilitates both disease progression and therapeutic resistance in prostate cancer. In fact, different forms of therapies such as androgen-deprivation, taxane-based chemotherapy, targeted kinase inhibition, and nutrient restriction, all induce significant cellular distress, and subsequently autophagy, which plays cyto-protective role in prostate cancer. The differential role of autophagy in prostate cancer cells is mainly dependent on the type of tumors, stage, and genetic context of cancer cells. Protein Kinase D1 is a serine-threonine kinase, a tumor-suppressor, which is down-regulated in advanced stage of prostate tumors. PKD1 is involved in many cellular functions, such as cell proliferation, apoptosis, cell adhesion and invasion. In this study we try to determine whether PKD1 causes autophagic cell death by activation of ER stress in prostate cancer cells. Methods: Prostate cancer cells expressing PKD1 (LNCaP and C4-2; C4-2-GFP; C4-2-GFP-PKD1) and null PKD1 (DU-145/PC-3) were used for the experiments. Cell viability assay was performed by MTS assay. CCL2 expression levels were quantified by ELISA. Cell migration assays were performed with cells pre-incubated with 3-Methyladenine (3-MA; autophagy inhibitor), or Salubrinal (SAL; ER stress inhibitor) or exogenously added CCL2 (100ng/mL). Immmunoblot experiments were performed using specific antibodies. Results: Our results suggest that PKD1 inhibits cell proliferation, migration and colonization, and arrest cells at G2/M phase. Our data strongly suggests that PKD1overexpressing cell activates Endoplasmic Reticulum (ER) stress-mediated autophagic cell death in prostate cancer cells compared to PKD1-null cells. Immunoblotting experiment suggested that C4-2-PKD1-GFP cells have suppressed ATG5/ATG7 and free ATG12 expression as compared to PKD1-null DU-145/PC-3 cells. These proteins are involved in the cyto-protective role of autophagy in prostate cancer cells. PKD1 also interacts and activates PERK expression, which is an initiator of Endoplasmic Reticulum stress (ER stress). PKD1-overexpressing C4-2-PKD-1-GFP and C4-2-GFP (vector control) cells inhibited nuclear translocation of oncogenic proteins such as c-Myc, ATG-5, p-NFKB-65 and β-catenin, and enhanced PERK and GSK-3β expression. Interestingly, PKD1 also suppressed the expression of p-AKT and mTOR and decreased glucose uptake in prostate cancer cells. Thus, PKD1 regulates glucose uptake with the involvement of AKT-mTOR-GSK-3β axis and decreases the nuclear translocation of c-Myc, ATG-5, p-NFKB-65 and β-catenin in prostate cancer cells. Conclusions: Our results strongly suggest that the PKD1 mediated modulation of autophagy and ER stress induced cell death can be useful for the augmentation of current chemotherapies used for prostate cancer treatment. Citation Format: Rishi K. Gara, Sonam Kumari, Sheema Khan, Neeraj Chauhan, Aditya Ganju, Subhash C. Chauhan, Meena Jaggi. Protein Kinase D1 induces autophagic cell death through activation of endoplasmic reticulum stress in prostate cancer 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 1001. doi:10.1158/1538-7445.AM2015-1001

Abstract 1334: Induction of autophagy by ormeloxifene and mevastatin through Protein Kinase D1 in prostate cancer cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Objective: Chemotherapy-induced emergence of drug resistance is one of the major limitations to treat prostate cancer. Numerous studies report that autophagic cell death functions as a suppressor of tumorigenesis in prostate cancer. Although chemotherapeutic drugs inhibit growth of cancer cells, they also activate chemokine, CCL2 which protects prostate cancer cells from autophagic cell death. Protein Kinase D1 (PKD1) plays multiple roles in the fundamental biological processes and is known as a tumor suppressor in prostate cancer. Here, we report for the first time that PKD1 inhibits CCL2 expression in prostate cancer cells. Therefore, we also investigated whether PKD1 modulation inhibits CCL2 and potentiates autophagic cell death. We have found a novel combination of mevastatin (MVS) and ormeloxifene (ORM), a non-steroidal, selective estrogen receptor inhibitor, effectively increases PKD1 expression and induces autophagic cell death in prostate cancer cells. Methods: Prostate cancer cells (C4-2) stably overexpressing PKD1 (C4-2-PKD1-GFP) or vector control (C4-2-GFP) were treated with ORM (10µM) and MVS (20µM) and their combination for 48h. Cell viability was performed by CellTiter 96® AQueous One Solution cell proliferation assay. CCL2 expression levels were quantified by ELISA as per the manufacturers instructions. Cell migration assays were performed with pre-incubation of 3-MA (5mM; 3-Methyladenine, an autophagy inhibitor) for 2h, or exogenously added CCL2 (100ng/mL) in the lower part of a Boyden chamber. The cells were treated with ORM alone or in combination with MVS for 18h for the analysis of proteins expression involved in autophagy. Immmunoblot experiments were performed using an autophagy sampler kit as per the manufacturers instructions. Results: Our results suggest that a combination of ORM and MVS increases PKD1 and inhibits CCL2 expression in prostate cancer cells. It inhibits cell proliferation, migration and metastasis of prostate cancer cells. Additionally, it was observed that ORM and MVS effectively inhibits CCL2 induced cell motility in PKD1 overexpressing cells, however the effect was not observed in PKD1 null cells. The PKD1 dependent inhibition of CCL2 expression activates autophagy as evidenced by activation of autophagy markers (LC3A, LC3B). It down-regulates survivin-1, Beclin-1 and NFκB-65, inducing autophagy in cancer cells. The cells treated with 3-MA and/or exogenous CCL2 abrogated the effects induced by MVS and ORM. Conclusion: Here, we propose for the first time a link between PKD1 and autophagy. We have found a novel combination of MVS and ORM that effectively increases PKD1 expression and induces autophagic cell death in prostate cancer cells. This study prospects combined therapies targeting PKD1/CCL2 and the PI3K/Akt/mTOR/survivin pathway as a valid strategy to overcome the resistance of prostate cancer cells. Citation Format: Rishi K. Gara, Sonam Kumari, Aditya Ganju, Murali M. Yallapu, Ankita Shah, Sheema Khan, Man M. Singh, Subhash C. Chauhan, Meena Jaggi. Induction of autophagy by ormeloxifene and mevastatin through Protein Kinase D1 in prostate cancer cells. [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 1334. doi:10.1158/1538-7445.AM2014-1334