Safe and targeted anticancer therapy for ovarian cancer using a novel class of curcumin analogs

Rath, Kellie S.; McCann, Georgia A.; Cohn, David E.; Rivera, Brian K.; Kuppusamy, Periannan; Selvendiran, Karuppaiyah
June 2013
Journal of Ovarian Research;2013, Vol. 6 Issue 1, p1
Academic Journal
A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey for a patient. Worldwide, approximately half of the individuals undergoing therapy for advanced cancer will succumb to the disease, or consequences of treatment. Well-known and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil, and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating side effects Therefore, development of new targeted anticancer therapies that can selectively kill cancer cells while sparing the surrounding healthy tissues is essential to develop more effective therapies. We have developed a new class of synthetic curcumin analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic (anticancer) activity, whereas the Nhydroxypyrroline (-NOH) moiety found on some variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity. The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer cell lines, and the safety has been evaluated in a number of non-cancerous cell lines. Both variations of the DAP compounds showed similar levels of cell death in ovarian cancer cells, however the compounds with the - NOH modification were less toxic to non-cancerous cells. The selective cytotoxicity of the DAP-NOH compounds suggests that they will be useful as safe and effective anticancer agents. This article reviews some of the key findings of our work with the DAP compounds, and compares this to some of the targeted therapies currently used in ovarian cancer therapy.


Related Articles

  • Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening. Laios, Alexandros; Mohamed, Bashir M.; Kelly, Lynne; Flavin, Richard; Finn, Stephen; McEvoy, Lynda; Gallagher, Michael; Martin, Cara; Sheils, Orla; Ring, Martina; Davies, Anthony; Lawson, Margaret; Gleeson, Noreen; D'Arcy, Tom; d'Adhemar, Charles; Norris, Lucy; Langhe, Ream; Saadeh, Feras Abu; O'Leary, John J.; O'Toole, Sharon A. // International Journal of Molecular Sciences;Jan2013, Vol. 14 Issue 1, p2085 

    Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were...

  • Insight into the toxic effects of cis-dichloridoplatinum(II) complexes containing 7-azaindole halogeno derivatives in tumor cells. Muchova, Tereza; Pracharova, Jitka; Starha, Pavel; Olivova, Radana; Vrana, Oldrich; Benesova, Barbora; Kasparkova, Jana; Travnicek, Zdenek; Brabec, Viktor // Journal of Biological Inorganic Chemistry;Jun2013, Vol. 18 Issue 5, p579 

    The cisplatin analogues cis-[PtCl(3ClHaza)] ( 1) and cis-[PtCl(3IHaza)] ( 2) (3ClHaza and 3IHaza are 3-chloro-7-azaindole and 3-iodo-7-azaindole, respectively) are quite toxic to ovarian tumor cells, with moderately better IC values than for cisplatin in the cisplatin-sensitive cell line A2780....

  • Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects. Florea, Ana-Maria; B├╝sselberg, Dietrich // Cancers;2011, Vol. 3 Issue 1, p1351 

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors...

  • Design, Synthesis and in vitro Cytotoxicity of a cis-Dichloroplatinum (II) Complex Linked to the Minor Groove Binder Stallimycin. Beraldi, Pier Giovanni; Tabrizi, Mojgan Aghazadeh; Pavani, Maria Giovanna; Del Carmen Nu├▒ez, Maria; Makaeva, Rimma; Gambari, Roberto; La Colla, Paolo; Romagnoli, Romeo // Drug Research / Arzneimittel-Forschung (Editio Cantor Verlag fur;Feb2003, Vol. 53 Issue 2, p107 

    Two potentially hydrophilic platinum (II) complexes 10 and 11 bound to the minor groove binder stallimycin (distamycin A, CAS 636-47-5) by L-cysteine and D,L-2,3-diaminopropionic acid have been synthesized. The in vitro cytotoxicity of both these complexes was evaluated against several cell...

  • Carboplatin/cisplatin/etoposide.  // Reactions Weekly;6/4/2011, Issue 1354, p14 

    The article presents a case report of a 38-year-old man who experienced neutropenic fevers, grade 2 dermatitis and grade 4 mucositis and a 66-year-old man who experienced hyponatraemia due to syndrome of inappropriate antidiuretic hormone hypersecretion, during neoadjuvant chemotherapy with...

  • Involvement of High Mobility Group B Proteins in Cisplatin-Induced Cytotoxicity in Squamous Cell Carcinoma of Skin. Sharma, Ashok; Ramanjaneyulu, Allam; Ray, Ruma; Rajeswari, Moganty R. // DNA & Cell Biology;Jul2009, Vol. 28 Issue 7, p311 

    Cis-diamminedichloroplatinum (II) (cisplatin) is a well-known anticancer drug with high potency and efficacy against various types of human cancers. Although it is widely accepted that the mechanism of cisplatin action is via apoptosis, there is enough evidence to support that cisplatin-induced...

  • BCL2 antagonist of cell death kinases, phosphatases, and ovarian cancer sensitivity to cisplatin. Bansal, Nisha; Marchion, Douglas C.; Bicaku, Elona; Yin Xiong; Ning Chen; Stickles, Xiaomang B.; Sawah, Entidhar Al; Wenham, Robert M.; Apte, Sachin M.; Gonzalez-Bosquet, Jesus; Judson, Patricia L.; Hakam, Ardeshir; Lancaster, Johnathan M. // Journal of Gynecologic Oncology;Mar2012, Vol. 23 Issue 1, p35 

    Objective: The BCL2 family proteins are critical mediators of cellular apoptosis and, as such, have been implicated as determinants of cancer cell chemo-sensitivity. Recently, it has been demonstrated that the phosphorylation status of the BCL2 antagonist of cell death (BAD) protein may...

  • Functional modulation of the mineralocorticoid receptor by cis-diamminedichloroplatinum (II). Iida, Takahisa; Makino, Yuchi; Okamoto, Kensaku; Yoshikawa, Noritada; Makino, Isao; Nakamura, Tetsuya; Tanaka, Hirotoshi // Kidney International;Oct2000, Vol. 58 Issue 4, p1450 

    Examines the suppression of mineralocorticoid receptor-dependent transcription by Cis-diamminedichloroplatinum (cDDP). Induction of cytotoxicity by DNA adduct formation; Characterization of cDDP; Association between reactive oxygen species and renal injury.

  • Targeted anti-vascular therapies for ovarian cancer: current evidence. Hall, M; Gourley, C; McNeish, I; Ledermann, J; Gore, M; Jayson, G; Perren, T; Rustin, G; Kaye, S // British Journal of Cancer;2/5/2013, Vol. 108 Issue 2, p250 

    Ovarian cancer presents at advanced stage in around 75% of women, and despite improvements in treatments such as chemotherapy, the 5-year survival from the disease in women diagnosed between 1996 and 1999 in England and Wales was only 36%. Over 80% of patients with advanced ovarian cancer will...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics