Mildred Acevedo-Duncan, PhD

Associations

• Molecular Oncology & Drug Discovery Program
• Cancer Biology & Evolution Program

Education & Training

Graduate:

• University of California, Riverside, MA
• University of California, Riverside, PhD

Fellowship:

• University of Florida, Gainesville, FL -
• University of South Florida, Tampa, FL -

My research investigates how protein kinase C (PKC)  isozymes interact to affect the cell cycle during cancer growth and development.  Information on the role of PKC isozymes in cell cycle regulation is important since PKC overproduction has been linked with the rapid growth rate of cancer cells. Our studies use human cancer cells in-vitro to determine how PKC inhibitors alone or in combination with other chemotherapeutics affect PKC,  cell proliferation and survival. The goals are to  identify PKC isozymes or PKC substrates which regulate the cell cycle in order to target and interfere with their activity, thereby providing selective therapeutic agents for controlling cancer cell proliferation.  Our research methods employ physical and biochemical isolation procedures, glioma PKC overexpressors, flow cytometry, scanning and transmission electron microscopy, and Western blotting.

• Khalid KM, Ratnayake WS, Apostolatos CA, Acevedo-Duncan M. Dual inhibition of atypical PKC signaling and PI3K/Akt signaling dysregulates c-Myc to induce apoptosis in clear cell Renal Cell Carcinoma. Front Oncol. 2024 Jan.13:1213715. Pubmedid: 38288105. Pmcid: PMC10823017.
• Sajan MP, Hansen BC, Acevedo-Duncan M, Kindy MS, Cooper DR, Farese RV. Roles of hepatic atypical protein kinase C hyperactivity and hyperinsulinemia in insulin-resistant forms of obesity and type 2 diabetes mellitus. MedComm (Beijing). 2021 Mar.2(1):3-16. Pubmedid: 34766133. Pmcid: PMC8491214.
• Dey A, Islam SMA, Patel R, Acevedo-Duncan M. The interruption of atypical PKC signaling and Temozolomide combination therapy against glioblastoma. Cell Signal. 2021 Jan.77:109819. Pubmedid: 33147518.
• Ratnayake WS, Apostolatos CA, Breedy S, Dennison CL, Hill R, Acevedo-Duncan M. Atypical PKCs activate Vimentin to facilitate prostate cancer cell motility and invasion. Cell Adh Migr. 2021 Dec.15(1):37-57. Pubmedid: 33525953. Pmcid: PMC7889213.
• Patel R, Islam SA, Bommareddy RR, Smalley T, Acevedo-Duncan M. Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression. Int J Oncol. 2020 Jun.56(6):1373-1386. Pubmedid: 32236625. Pmcid: PMC7170046.
• Islam SMA, Dey A, Patel R, Smalley T, Acevedo-Duncan M. Atypical Protein Kinase-C inhibitors exhibit a synergistic effect in facilitating DNA damaging effect of 5-fluorouracil in colorectal cancer cells. Biomed Pharmacother. 2020 Jan.121:109665. Pubmedid: 31810137.
• BommaReddy RR, Patel R, Smalley T, Acevedo-Duncan M. Effects of Atypical Protein Kinase C Inhibitor (DNDA) on Lung Cancer Proliferation and Migration by PKC-ι/FAK Ubiquitination Through the Cbl-b Pathway. Onco Targets Ther. 2020 Feb.13:1661-1676. Pubmedid: 32158232. Pmcid: PMC7047975.
• Smalley T, Metcalf R, Patel R, Islam SMA, Bommareddy RR, Acevedo-Duncan M. The Atypical Protein Kinase C Small Molecule Inhibitor ζ-Stat, and Its Effects on Invasion Through Decreases in PKC-ζ Protein Expression. Front Oncol. 2020 Feb.10:209. Pubmedid: 32175276. Pmcid: PMC7056911.
• Vardhan H, Nafady A, Al-Enizi AM, Khandker K, El-Sagher HM, Verma G, Acevedo-Duncan M, Alotaibi TM, Ma S. Investigation of the Anticancer Activity of Coordination-Driven Self-AssembledTwo-Dimensional Ruthenium Metalla-Rectangle. Molecules. 2019 Jun.24(12). Pubmedid: 31248221. Pmcid: PMC6630691.
• Apostolatos AH, Apostolatos CA, Ratnayake WS, Neuger A, Sansil S, Bourgeois M, Acevedo-Duncan M. Preclinical testing of 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide: a potent protein kinase C-ι inhibitor as a potential prostate carcinoma therapeutic. Anticancer Drugs. 2019 Jan.30(1):65-71. Pubmedid: 30204596. Pmcid: PMC6287896.
• Smalley T, Islam SMA, Apostolatos C, Apostolatos A, Acevedo-Duncan M. Analysis of PKC-ζ protein levels in normal and malignant breast tissue subtypes. Oncol Lett. 2019 Feb.17(2):1537-1546. Pubmedid: 30675210. Pmcid: PMC6341665.
• Islam SMA, Patel R, Bommareddy RR, Khalid KM, Acevedo-Duncan M. The modulation of actin dynamics via atypical Protein Kinase-C activated Cofilin regulates metastasis of colorectal cancer cells. Cell Adh Migr. 2019 Dec.13(1):106-120. Pubmedid: 30417717. Pmcid: PMC6527392.
• Apostolatos AH, Ratnayake WS, Win-Piazza H, Apostolatos CA, Smalley T, Kang L, Salup R, Hill R, Acevedo-Duncan M. Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade. Int J Oncol. 2018 Nov.53(5):1836-1846. Pubmedid: 30226591. Pmcid: PMC6192717.
• Ratnayake WS, Apostolatos CA, Apostolatos AH, Schutte RJ, Huynh MA, Ostrov DA, Acevedo-Duncan M. Oncogenic PKC-ι activates Vimentin during epithelial-mesenchymal transition in melanoma; a study based on PKC-ι and PKC-ζ specific inhibitors. Cell Adh Migr. 2018 May.12(5):447-463. Pubmedid: 29781749. Pmcid: PMC6363030.
• Anisul Islam SM, Patel R, Acevedo-Duncan M. Protein Kinase C-ζ stimulates colorectal cancer cell carcinogenesis via PKC-ζ/Rac1/Pak1/β-Catenin signaling cascade. Biochim Biophys Acta Mol Cell Res. 2018 Apr.1865(4):650-664. Pubmedid: 29408512.
• Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M. Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis. Int J Oncol. 2017 Nov.51(5):1370-1382. Pubmedid: 29048609. Pmcid: PMC5642393.
• Walker KK, Martínez-Mier EA, Soto-Rojas AE, Jackson RD, Stelzner SM, Galvez LC, Smith GJ, Acevedo M, Dandelet L, Vega D. Midwestern Latino caregivers' knowledge, attitudes and sense making of the oral health etiology, prevention and barriers that inhibit their children's oral health: a CBPR approach. BMC Oral Health. 2017 Mar.17(1):61. Pubmedid: 28253872. Pmcid: PMC5335721.
• Sajan MP, Acevedo-Duncan ME, Standaert ML, Ivey RA, Lee M, Farese RV. Akt-dependent phosphorylation of hepatic FoxO1 is compartmentalized on a WD40/ProF scaffold and is selectively inhibited by aPKC in early phases of diet-induced obesity. Diabetes. 2014 Aug.63(8):2690-2701. Pubmedid: 24705403. Pmcid: PMC4113067.
• Desai SR, Pillai PP, Patel RS, McCray AN, Win-Piazza HY, Acevedo-Duncan ME. Regulation of Cdk7 activity through a phosphatidylinositol (3)-kinase/PKC-ι-mediated signaling cascade in glioblastoma. Carcinogenesis. 2012 Jan.33(1):10-19. Pubmedid: 22021906. Pmcid: PMC4662058.
• Sajan MP, Nimal S, Mastorides S, Acevedo-Duncan M, Kahn CR, Fields AP, Braun U, Leitges M, Farese RV. Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι. Metabolism. 2012 Apr.61(4):459-469. Pubmedid: 22225955. Pmcid: PMC3786325.
• Pillai P, Desai S, Patel R, Sajan M, Farese R, Ostrov D, Acevedo-Duncan M. A novel PKC-ι inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma. Int J Biochem Cell B. 2011 May.43(5):784-794. Pubmedid: 21315177.
• Win HY, Acevedo-Duncan M. Role of protein kinase C-iota in transformed non-malignant RWPE-1 cells and androgen-independent prostate carcinoma DU-145 cells. Cell Proliferat. 2009 Apr.42(2):182-194. Pubmedid: 19243387. Pmcid: PMC6496878.
• Win HY, Acevedo-Duncan M. Atypical protein kinase C phosphorylates IKKalphabeta in transformed non-malignant and malignant prostate cell survival. Cancer Lett. 2008 Nov.270(2):302-311. Pubmedid: 18571841.
• Matthews JA, Belof JL, Acevedo-Duncan M, Potter RL. Glucosamine-induced increase in Akt phosphorylation corresponds to increased endoplasmic reticulum stress in astroglial cells. Mol Cell Biochem. 2007 Apr.298(1-2):109-123. Pubmedid: 17136481.
• Bicaku E, Patel R, Acevedo-Duncan M. Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota in human glioma cells. Tissue Cell. 2005 Feb.37(1):53-58. Pubmedid: 15695176.
• Matthews JA, Acevedo-Duncan M, Potter RL. Selective decrease of membrane-associated PKC-alpha and PKC-epsilon in response to elevated intracellular O-GlcNAc levels in transformed human glial cells. Biochim Biophys Acta. 2005 Apr.1743(3):305-315. Pubmedid: 15843043.
• Acevedo-Duncan M, Russell C, Patel S, Patel R. Aloe-emodin modulates PKC isozymes, inhibits proliferation, and induces apoptosis in U-373MG glioma cells. Int Immunopharmacol. 2004 Dec.4(14):1775-1784. Pubmedid: 15531293.
• Acevedo-Duncan M, Patel R, Whelan S, Bicaku E. Human glioma PKC-iota and PKC-betaII phosphorylate cyclin-dependent kinase activating kinase during the cell cycle. Cell Prolif. 2002.35:23-36. Pubmedid: 11856176.
• Bicaku E, Acevedo-Duncan M. Ultrastructural study of protein kinase C-betaII localization during the cell cycle of human glioma cells. Tissue Cell. 2001.33(1):55-62. Pubmedid: 11292171.
• Yamamoto M, Acevedo-Duncan M, Chalfant CE, Patel NA, Watson JE, Cooper DR. Acute glucose-induced downregulation of PKC-betaII accelerates cultured VSMC proliferation. Am J Physiol Cell Physiol. 2000 Sep.279(3):C587-C595. Pubmedid: 10942708.
• Acevedo-Duncan M, Pearlman J, Zachariah B. Sensitivity of human glioma U-373MG cells to radiation and the protein kinase C inhibitor, calphostin C. Cell Prolif. 2000.34(1):31-41. Pubmedid: 11284917.
• Cooper DR, Watson JE, Patel N, Illingworth P, Acevedo-Duncan M, Goodnight J, Chalfant CE, Mischak H. Ectopic expression of protein kinase CbetaII, -delta, and -epsilon, but not -betaI or -zeta, provide for insulin stimulation of glucose uptake in NIH-3T3 cells. Arch Biochem Biophys. 1999 Dec.372(1):69-79. Pubmedid: 10562418.
• Yamamoto M, Acevedo-Duncan M, Chalfant C, Patel N, Watson J, Cooper D. The roles of protein kinase C beta I and beta II in vascular smooth muscle cell proliferation. Exp Cell Res. 1998 May.240(2):349-358. Pubmedid: 9597008.
• Acevedo-Duncan M, Zhang R, Cooper DR, Greenberg HM. Effects of interferon and PKC modulators on human glioma protein kinase C, cell proliferation, and cell cycle. Neurochem Res. 1997 Jul.22(7):775-784. Pubmedid: 9232628.
• Acevedo-Duncan M, Collins J, Zhang R, Haller E, Chalfant CE, Cooper DR. In situ effects of interferon on human glioma protein kinase C-alpha and -beta ultrastructural localization. Cell Growth Differ. 1995 Nov.6(11):1353-1365. Pubmedid: 8562473.
• Acevedo-Duncan M, Zhang R. Heterogeneity of protein kinase C activity in human U-373 and G-26 mice glioma cells. Biochem Biophys Res Commun. 1994.205(1):127-134.
• Acevedo-Duncan M, Cooper DR, Standaert ML, Farese RV. Immunological evidence that insulin activates protein kinase C in BC3H-1 myocytes. FEBS Lett. 1989 Feb.244(1):174-176. Pubmedid: 2647516.
• Bai W, Oliveros-Saunders B, Wang Q, Acevedo-Duncan M, Nicosia S. Estrogen stimulation of ovarian surface epithelial cell proliferation. In Vitro Cell Dev-An. 36(10):657-666. Pubmedid: 11229598.