H460 Human Cancer Cell Lines Research Articles

C18-Diterpenoid alkaloids from Delphinium anthriscifolium var. majus

Five new C18-diterpenoid alkaloids, anthriscifoltines C-G (1–5), along with four known diterpenoid alkaloids anthriscifolcines C-F (6–9), were isolated from the extract of Delphinium anthriscifolium var. majus. Their structures were elucidated by extensive spectroscopic analyses (including 1D-, 2D-NMR, and HR-ESI-MS). Compounds 1–5 were also evaluated for their cytotoxic activity against MCF-7, HepG2, and H460 human cancer cell lines.

Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 μM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers.

Three cytotoxic Annonaceous acetogenins from the seeds of Annona squamosa

Three new Annonaceous acetogenins, squamocin-IV (1), squamocin-V (2) and squamoxinone-E (3), together with seven other known Annonaceous acetogenins (4–10) were isolated from the seeds of Annona squamosa. The structures of all of the isolates were established and characterized through spectral and chemical methods. The new Annonaceous acetogenins 1–3 were evaluated for their cytotoxicity against the Hep-G2, SMMC-7721, BEL-7402, BGC-803 and H460 human cancer cell lines. Compound 3 exhibited the best cytotoxic activity, with IC50 values of 0.103, 0.687, 4.19, 0.43 and 6.56μg/mL, respectively for the cell lines above; meanwhile, Compound 1 showed selective cytotoxic activity against H460, with an IC50 value of 0.049μg/mL. The first mono-ACG (2) composed of 38 carbons was discovered.

Three new pyrrolizidine alkaloids derivatives from Liparis nervosa

Abstract Three new pyrrolizidine alkaloids, nervosine VII ( 1 ), nervosine VIII ( 2 ) and nervosine IX ( 3 ) were isolated from the whole plant extract of Liparis nervosa . Their structures were elucidated by extensive spectroscopic analyses (including 1D, 2D NMR, and HR-ESI-MS) and chemical methods. Compounds 1–3 were evaluated for their cytotoxic activity against A549, MCF-7and H460 human cancer cell lines.

Four cytotoxic annonaceous acetogenins from the seeds of Annona squamosa

Four new annonaceous acetogenins (ACGs), squamocin-I (1), II (2) and III (3) and squamoxinone-D (4), together with seven known ACGs (5–11), were isolated from the seeds of Annona squamosa. The structures of all isolates were elucidated and characterised by spectral and chemical methods. Compounds 1–4 were evaluated for their cytotoxicities against Hep G2, SMMC 7721, BEL 7402, BGC 803 and H460 human cancer cell lines. Compound 1 exhibited better potent activity than the positive compound and compound 3 shows selectively cytotoxical activity against H460 with IC50 values of 0.0492 μg/ml.

Mechanisms of nicotine-induced resistance to treatment with chemotherapy and radiotherapy

e22008 Background: Nicotine (NIC), used for smoking cessation in cancer patients, is associated with increased tumor growth, angiogenesis, migration, invasion, growth factor production, and inhibition of apoptosis. The effects of NIC on the efficacy of radiotherapy (XRT) and/or chemotherapy (CT) have not been well characterized. Methods: A review of the literature produced a construct demonstrating that NIC generates more than 100 interactions with 40 proteins involved in tumor promotion and progression. From this construct, nicotinic acetylcholine receptors (nAChR), PI3K/Akt, and MAPK were identified as potential critical upstream targets modulating the effects of NIC. The effect of NIC on cell proliferation, cell survival, and protein activation was analyzed following CT, XRT, or chemoradiotherapy (CRT) in FaDu, A549, and H460 human cancer cell lines. Results: Proliferation measured with the WST-1 (tetrazolium) assay demonstrated that NIC increased proliferation following cisplatin, XRT, and cisplatin with XRT. NIC administration increased cell survival (colony survival) following XRT and following CT (cisplatin, doxorubicin, or etoposide) regimens in all cell lines. nAChR expression was verified in each cell line using Western blot. Non-specific inhibition of nAChR demonstrated no consistent effect on preventing NIC induced resistance to CT, XRT, or CRT; however, specific inhibition of the alpha-3- or alpha-7-nAChR had variable cell specific ability to prevent NIC induced resistance. Inhibition of MAPK activity (using PD98059) produced marked reduction in proliferation of all cell lines, but generally had no effect on NIC induced resistance. PI3K inhibition (using LY294002) generally increased sensitivity to cisplatin and XRT; however, some PI3K activity was required to achieve the full effect of cisplatin. NIC prevented LY294002 induced sensitization to chemotherapy with no effect on sensitization to XRT. Conclusions: Nicotine induces a broad spectrum of resistance to CT, XRT, and CRT and serves as an excellent model of treatment resistance. Mechanisms of NIC induced resistance to CT and XRT appear to diverge. These findings have significant clinical implications including smoking cessation, treatment efficacy, and outcomes research in cancer patients. No significant financial relationships to disclose.

Withaphysanolide A, a novel C-27 norwithanolide skeleton, and other cytotoxic compounds from Physalis divericata

A novel C-27 norwithasteroid, withaphysanolide A ( 1) containing a pyran ring was isolated from the aerial parts of Physalis divericata. Four known withaphysalins ( 2– 5) and five physalins ( 6– 10) were also isolated. The structural assignment for 1 was done based on spectroscopic and single-crystal X-ray diffraction data. Logical biosynthetic pathways were postulated. Compounds 6, 7, and 10 displayed potent cytotoxic activity against HCT-116 and H460 human cancer cell lines, with IC 50 values less than 2.0 μM.