Promising Anticancer Activity of [Bis(1,8-quinolato)palladium (II)] Alone and in Combination.

Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds as well have been investigated for their anticancer activity. In the present study, we describe synthesis, characterization, and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumor activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines.

Enhanced Accumulation of Cisplatin in Ovarian Cancer Cells from Combination with Wedelolactone and Resulting Inhibition of Multiple Epigenetic Drivers.

Purpose: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin.

Methods: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780 (cisplatin resistant) and A2780 Resistance factor (RF) of drugs was determined in these three cell lines.

Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding.

Context And Objective: Cisplatin is a platinum drug in current clinical use for the treatment of cervical cancer. However, drug toxicity and resistance are its two major limitations. The aim of this investigation was to test the cytotoxic activity of potential phytochemicals alone and in combination with cisplatin in cervical cancer cells.

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models.

In the present study, cisplatin, artemisinin, and oleanolic acid were evaluated alone, and in combination, on human ovarian A2780, A2780, and A2780 cancer cell lines, with the aim of overcoming cisplatin resistance and side effects. Cytotoxicity was assessed by MTT reduction assay. Combination index (CI) values were used as a measure of combined drug effect.

Prospects of Wedelolactone as a Chemotherapeutic Agent in Gynecological Cancers; Clue From its In Vitro and In Silico Investigation.

Background: Identification and development of new drug candidates to be used singly or in combination therapy is critical in anticancer research. In recent years, accumulating evidence encouraged us to investigate the anti-proliferative effects of a small and emerging phytochemical Wedelolactone (WDL) in estrogen-dependent and independent multiple gynecological tumor models.

Objective: The aim of this study was to investigate the growth inhibitory effect of WDL on estrogen- dependent and independent gynecological cell lines and to explore its inhibitory potential towards key targets through in silico study.

Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer.

Background: Colorectal cancer is the third most commonly diagnosed cancer in the world, causing many deaths every year. Combined chemotherapy has opened a new horizon in treating colorectal cancer. The objective of the present study is to investigate the activity of oxaliplatin in combination with emetine and patulin against colorectal cancer models.

Changes in the in vitro activity of platinum drugs when administered in two aliquots.

Background: The management of ovarian cancer remains a challenge. Because of the lack of early symptoms, it is often diagnosed at a late stage when it is likely to have metastasized beyond ovaries. Currently, platinum based chemotherapy is the primary treatment for the disease.

Synthesis of tris(quinoline)monochloroplatinum(II) Chloride and its Activity Alone and in Combination with Capsaicin and Curcumin in Human Ovarian Cancer Cell Lines.

Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. With the idea that the difference may translate into an altered spectrum of activity, monofunctional planaramineplatinum(II) complex tris(quinoline)monochloro-platinum chloride (coded as LH5) was synthesized and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistnat A2780 (A2780(ZD0473R)) cancer cell lines alone and in combination with the phytochemicals capsaicin (Caps) and curcumin (Cur) as a function of concentration and sequence of administration. Cell viability was quantified using the MTT reduction assay, while combination was used as a quantitative measure of the combined drug action.

Combination of Genistein and Cisplatin with Two Designed Monofunctional Platinum Agents in Human Ovarian Tumour Models.

A great amount of research effort has been directed at platinum compounds that bind with DNA differently from cisplatin with the idea that the difference may translate into an altered spectrum of activity. Recently research has also been directed at applying combinations of platinum agents with tumour-active phytochemicals with the aim of providing a means of overcoming platinum resistance in ovarian cancer. Herein we report the synthesis of monofunctional platinum tris(3-hydroxypyridine)chloroplatinum(II) chloride (coded as LH1) and tris(imidazole)chloroplatinum(II) chloride (coded as LH2), and their activity alone and in combination with genistein and cisplatin against human ovarian A2780, cisplatin-resistant A2780(cisR) and picoplatin-resistant A2780(ZD0473R) cancer cell lines.

Monofunctional Platinum-containing Pyridine-based Ligand Acts Synergistically in Combination with the Phytochemicals Curcumin and Quercetin in Human Ovarian Tumour Models.

With the idea that platinum compounds that bind with DNA differently than cisplatin may be better-able to overcome platinum resistance in ovarian tumor, the monofunctional platinum complex tris(imidazo(1,2-α)pyridine) chloroplatinum(II) chloride (coded as LH6) has been synthesized and investigated for its activity, alone and in combination with the phytochemicals curcumin and quercetin, against human ovarian A2780, A2780(cisR) and A2780(ZD0473R) cancer cell lines. LH6 is found to be more active than cisplatin against the resistant cell lines and its bolus combinations with curcumin and quercetin are found to produce more pronounced cell kill. Whereas platinum accumulation from cisplatin is found to increase almost linearly with time, that from LH6 reaches a maximum at 4 h and is somewhat lowered at 24 h.

Synthesis of a monofunctional platinum compound and its activity alone and in combination with phytochemicals in ovarian tumor models.

Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. In this study, a new monofunctional planaramineplatinum(II) complex, namely tris(8-hydroxyquinoline)monochloroplatinum(II) chloride (coded as LH3), was synthesised and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistant A2780 (A2780(ZD0473R)) cancer cell lines, alone and in combination with the phytochemicals curcumin, genistein and resveratrol. Cellular levels of glutathione in A2780 and A2780(cisR) cell lines before and after treatment with LH3 and its combinations with genistein and curcumin were also determined.

Synergism from combinations of tris(benzimidazole) monochloroplatinum(II) chloride with capsaicin, quercetin, curcumin and cisplatin in human ovarian cancer cell lines.

In the present study, synergism in activity from the sequenced combinations of monofunctional platinum tris(benzimidazole)monochloroplatinum(II) chloride (coded as LH4) with capsaicin, quercetin, curcumin and cisplatin was investigated as a function of sequence of administration in a number of human ovarian tumor models. Cellular accumulations of platinum and the levels of platinum-DNA binding were also determined for the 0/0 h and 4/0 sequences of administration. LH4 was found to be more active against the resistant A2780(cisR) and A2780(ZD0473R) cell lines than the parent A2780 cell line.

Synthesis and activity of three new trinuclear platinums with cis-geometry for terminal metal centres.

Background: As compared to cisplatin, trinuclear platinum compounds such as BBR3464 and DH6Cl have an altered spectrum of activity possibly because they form long-range adducts with DNA as against mainly intrastrand 1,2-bifunctional adducts formed by cisplatin and its analogues. Because of the labilizing effect associated with the trans-geometry, the compounds are expected to break down inside the cell thus serving to reduce the number of long-range adducts formed. In contrast, trinuclear platinum complexes with cis-geometry for the terminal metal centres would be less subject to such breakdown and hence may produce a greater number of long-range inter- and intrastrand adducts with the DNA.

Synthesis and antitumour activity of a new trinuclear platinum compound [{cis-PtCl(NH3)2μ {trans-Pt(3-hydroxypyridine)2H2N(CH2)5NH2)2}] Cl4 in human ovarian cancer cells.

A trinuclear platinum compound with a cis-geometry for the terminal metal centers coded as QH5 has been synthesized and investigated for activity against the human ovarian A2780, A2780(cisR) and A2780(ZD0473R) cancer cell lines. Cellular accumulation of platinum, level of platinum-DNA binding and nature of interaction of the compound with pBR322 plasmid DNA have also been determined. QH5 is found to be more active than cisplatin against all the three cell lines and to have much lower resistant factors than cisplatin.

Combinations of platinums and selected phytochemicals as a means of overcoming resistance in ovarian cancer.

Cancer sufferers are often found to use herbal products along with targeted therapy although not much information (whether beneficial or harmful) is available about the effects of such combinations. In this study, we investigated synergism from the combination of platinum drugs and a number of tumour-active phytochemicals including curcumin, epigallocatechin-3-gallate, thymoquinone, genistein, resveratrol, betulinic acid and ursolic acid in three human ovarian cancer cell lines A2780, A2780(cisR) and A2780(ZD0473R), as a function of concentration and the sequence of administration. Both the dose-effect curves and combination indices show that the binary combinations of platinum drugs with the phytochemicals exert concentration- and sequence-dependent synergism in the cell lines.

Carboplatin and oxaliplatin in sequenced combination with bortezomib in ovarian tumour models.

Background: Ovarian cancer remains an on-going challenge mainly due to the development of drug resistance and also because the cancer is likely to have metastasized at the time of diagnosis. Currently, chemotherapy based on platinum drugs such as cisplatin is the primary treatment for the disease. Copper transporter 1 is involved in the transport of cisplatin into the cell, but is also down-regulated by the drug.

Anti-proliferative and pro-apoptotic effects from sequenced combinations of andrographolide and cisplatin on ovarian cancer cell lines.

Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis paniculata and reported to be active against several cancer cell lines. However, few in-depth studies have been carried out on its effects on ovarian cancer cell lines alone or in combination with cisplatin (Cis), which is commonly used to treat ovarian cancer. The aim of this study was to determine the anti-proliferative and apoptotic effects of Andro administered alone and in combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h, 24/0 h and 0/24 h.

Studies on the activity of two Trans-planaramine platinum(II) complexes coded as DH4 and DH5 in human ovarian tumour models.

In this article, we report the synthesis and the in vitro activity of trans-bis(2-methylimidazole)dichloroplatinum(II) (coded as DH4) and trans-(ammino)(2,3-diaminopyridine) dichloroplatinum(II) (coded as DH5) in the human ovarian tumour models. DH4 is less active than cisplatin against the parental A2780 cell line but more active than cisplatin against the resistant A2780(cisR) cell line, thus indicating that it is better able to overcome mechanisms of resistance operating in the A2780(cisR) line. In contrast, DH5 is less active than cisplatin against all three cell lines.

Epigallocatechin gallate acts synergistically in combination with cisplatin and designed trans-palladiums in ovarian cancer cells.

In this study, synergism in activity from the sequenced combinations of three trans-palladiums (denoted as TH5, TH6 and TH7) with green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), as well as that with cisplatin, was investigated in a number of human ovarian tumour models as a function of sequence of administration. Cellular accumulation of platinum and palladium, and the levels of platinum-DNA and palladium-DNA binding were also determined for the 0/4 h and 0/0 h sequences of administration. The results of the study show that co-administration of cisplatin with EGCG (0/0 h) produces weak synergism in both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780(cisR)) cell lines whereas (0/4 h) administration produces pronounced synergism in both.

Studies on combination of platinum drugs cisplatin and oxaliplatin with phytochemicals anethole and curcumin in ovarian tumour models.

Chemopreventative phytochemicals having antitumour and antioxidant properties can overcome problems of chemoresistance and nonspecific toxicity towards normal cells that are associated with platinum-based chemotherapy against cancer. These agents exert their effects by bringing into play numerous cellular proteins that in turn affect multiple steps in pathways leading to tumourigenesis. In this study, combinations of two cytotoxic phytochemicals anethole and curcumin were applied in binary combination with platinum drugs cisplatin and oxaliplatin to three epithelial ovarian cancer cell lines: A2780 (parent), A2780(cisR) (cisplatin-resistant) and A2780(ZD0473R) (ZD0473-resistant).

Synthesis and cytotoxicity of three trans-palladium complexes containing planaramine ligands in human ovarian tumor models.

The present study deals with the synthesis, characterization, and activity against human ovarian cancer cell lines A2780, A2780(cisR), A2780(ZD0473R), and SKOV-3 of three trans-planaramine-palladium(II) complexes of the form trans-PdL(2)Cl(2), coded as EH1, EH3, and EH4, for which L = 2-methylpyridine, imidazole, and 1,2-α-imidazopyridine, respectively. The cellular accumulation of palladium, palladium-DNA binding levels, and the nature of interactions of the compounds with salmon sperm and pBR322 plasmid DNA were also determined. All three compounds were found to be less active than cisplatin, but unlike cisplatin they were found to be equally or more active against the resistant cell lines A2780(cisR) and A2780(ZD0473R) than against the parent cell line A2780.

Synthesis and activity of [{Cis-PtCl(NH3)2}2µ{trans-Pt(3-Hydroxypyridine)2(H2N(CH2)6NH2)2}]Cl4 in the human ovarian tumour models.

A novel trinuclear platinum compound with a cis-geometry for terminal metal centres coded as QH1 has been synthesized, characterized and investigated for activity against the human ovarian A2780, A2780cisR and A2780ZD0473R cancer cell lines. The cellular accumulation of platinum, level of platinum-DNA binding and the nature of interaction of the compound with pBR322 plasmid DNA have also been determined. QH1 is found to be more active against the resistant cell lines than the parent cell line, thus indicating that the compound has been able to overcome mechanisms of resistance operating in the A2780cisR and A2780ZD0473R cell lines.

Synergism from combination of cisplatin and multicentred platinums coded as DH6Cl and TH1 in the human ovarian tumour models.

Development of drug resistance and the presence of dose-limiting side-effects remain the two main problems in cancer chemotherapy. Combination of drugs with different mechanisms of action can offer a distinct advantage over monotherapy in overcoming drug resistance and reducing the side-effects. In this study synergism in activity from the combinations of cisplatin (Cis) with two multicentred platinum complexes coded as TH1 and DH6Cl in the human ovarian A2780, A2780cisR and A27800473R cancer cell lines had been investigated.

Combinations of resveratrol, cisplatin and oxaliplatin applied to human ovarian cancer cells.

In this study, combinations of resveratrol with platinum drugs cisplatin and oxaliplatin were administered to human ovarian A2780, A2780(cisR) and A2780(ZD0473R) cell lines with the aim of offering a means of overcoming drug resistance. Cell viability was quantified using the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combination indices and dose response curves were used as measures of the combined drug action.