Schiff base-nickel, palladium, and platinum complexes derived from N-cyclohexyl hydrazine carbothioamide and 3-hydroxy-4-methoxybenzaldehyde: Selective antiproliferative and proapoptotic effects against colorectal carcinoma.

The bidentate N-cyclohexyl-2-(3-hydroxy-4-methoxybenzylidene)hydrazine-1-carbothioamide Schiff base ligand (HL) was coordinated to divalent nickel, palladium and platinum ions to form square planar complexes. The nickel and palladium complexes, [NiL2 ], [PdL2 ] form square planar complexes with 2:1 ligand to metal ratio. The platinum complex, [PtL(dmso)Cl] formed a square planar complex with 1:1 ligand to metal ratio. Platinum undergoes in situ reaction with DMSO before complexing with the ligand in solution. The cytotoxicity of HL, [NiL2 ], [PdL2 ], and [PtL(dmso)Cl] were evaluated against human colon cancer cell line (HCT-116), human cervical cancer (Hela) cell line, melanoma (B16F10) cells, and human normal endothelial cell lines (Eahy926) by MTT assay. The [NiL2 ] complex displayed selective cytotoxic effect against the HCT 116 cancer cell line with IC50 of 7.9 ± 0.2 µM. However, HL, [PdL2 ], and [PtL(dmso)Cl] only exhibited moderate cytotoxic activity with IC50 = 75.9 ± 2.4, 100.0 ± 1.8, and 101.0 ± 3.6 µM, respectively. The potent cytotoxicity of [NiL2 ] was characterized using Hoechst and Rhodamine assays. The nickel complex, [NiL2 ], caused remarkable nuclear condensation and reduction in mitochondrial membrane potential. In addition, molecular docking studies confirms that [NiL2 ] possesses significant binding efficiency with Tyrosine kinase. Altogether, the results revealed that [NiL2 ] exhibits cytotoxicity against the cancer cells via Tyrosine kinase-induced proapoptosis pathway. This study demonstrates that the [NiL2 ] complex could be a promising therapeutic agent against colorectal carcinoma.

Toxicological studies of Orthosiphon stamineus (Misai Kucing) standardized ethanol extract in combination with gemcitabine in athymic nude mice model.

Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment. Gemcitabine, the first line anticancer drug has reduced efficacy due to acquired resistance. The current study evaluates the toxicological effects of Orthosiphon stamineus (O.s) and its marker compound (rosmarinic acid) in combination with gemcitabine. O.s (200 or 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally and gemcitabine (10 mg/kg/3 days) intraperitoneally either alone or in combination treatment for fourteen days. Parameters including blood serum biochemistry, hematology, myeloid-erythroid ratio, incident of lethality, and histopathological analysis of liver, kidney, and spleen tissues were studied. Neither, individual drugs/extract nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude mice when compared to control group. Toxicological data obtained from this study will help to select the best doses of chemo-herbal combination for future pancreatic xenograft tumor studies.

Antihyperlipidemic, Antioxidant and Cytotoxic Activities of Methanolic and Aqueous Extracts of Different Parts of Star Fruit.

BACKGROUND: Star fruit (Averrhoa carambola) is a well-known plant in Malaysia which bears a great significance in traditional medicine. OBJECTIVES: This study aimed to evaluate the antihyperlipidemic effect, antioxidant potential and cytotoxicity of aqueous and methanolic extracts of ripe and unripe fruits, leaves and stem of A. carambola. METHODS: Antihyperlipidemic activity was assessed in poloxamer-407 (P-407) induced acute hyperlipidemic rat's model. The antioxidant activity was assessed in vitro using 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging, 1-diphenyl-2-dipicrylhydrazyl radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP) assays. In addition, cytotoxicity of A. carambola extracts was assessed using MTS assay on four leukemic cell lines (human colon cancer, human promyeloid leukemia, erythroid leukemia, acute myeloid leukemia) and one normal cell (human umbilical vein endothelial cells). RESULTS: Methanolic extract of leaves had the most potent antihyperlipidemic activity in P-407 model, whereby it significantly reduced serum levels of total cholesterol (P<0.01), triglycerides (P<0.01), low-density lipoprotein (P<0.05), verylow- density lipoprotein (P<0.01) and atherogenic index (P<0.01). On the other hand, methanolic extracts of A. carambola stem and leaves showed the strongest antioxidant activity. Total phenolic and flavonoid contents of the extracts exhibited significant correlations with antioxidant but not with antihyperlipidemic activities. All plant parts showed no cytotoxic effect on the selected cancer or normal cell lines. CONCLUSION: Antihyperlipidemic activity of different parts of A. carambola is greatly affected by extraction solvents used. Methanolic extract of A. carambola leaves exhibited higher antihyperlipidemic and antioxidant potentials compared to other parts of the plant.